| |
Important Note: The following information
is provided for your education. It should not be relied upon
for personal diagnosis or treatment. If you believe that a particular
therapy applies to you or someone you care about, be sure to
consult a doctor before trying it.
Arthritis Research: 2002-2006
Curr Opin Rheumatol. 2006 Sep;18(5):526-30.
Who, when, and why total joint replacement surgery? The patient's
perspective.
Hawker GA.
PURPOSE OF REVIEW: Although total joint replacement is an effective treatment
for advanced arthritis, many whom might benefit are unwilling to consider this
procedure. This review highlights advances in understanding of patients'
perceptions of total joint replacement. RECENT FINDINGS: Research shows that
patients' willingness to consider total joint replacement varies by sex,
race/ethnicity, and socioeconomic status as a result of systematic differences
in knowledge and beliefs about the procedure. Individuals with low socioeconomic
status and minorities view the procedure less favorably than their wealthier,
white counterparts, possibly partly explaining disparity in rates of use of the
procedure among these groups. Among those undergoing total joint replacement, up
to 30% experience a suboptimal outcome or are dissatisfied with results. Early
work suggests that patients' expectations and self-efficacy are important
potential predictors of postoperative outcome. Patient information needs
regarding total joint replacement vary significantly and possibly systematically
by sex and race/ethnicity. Available information materials may not address the
concerns of many individuals contemplating the procedure, posing a potential
barrier to surgery. SUMMARY: Targeted culturally sensitive knowledge
dissemination strategies are needed to improve the knowledge and beliefs of
people with hip/knee arthritis about total joint replacement.
-----
Arthroscopy. 2006 Aug;22(8):902.e1-3.
Arthroscopic treatment of septic arthritis of the hip.
Nusem I, Jabur MK, Playford EG.
Department of Orthopaedics, Logan Hospital, Meadowbrook, Australia. iulian_nusem@health.qld.gov.au
Arthrotomy is considered standard treatment for septic arthritis of the hip; the
procedure may be complicated by avascular necrosis or postoperative hip
instability. Arthroscopic treatment of patients with this condition is still not
an established technique, despite its minimally invasive nature and the fact
that it is associated with low morbidity. A 3-portal arthroscopic technique by
Byrd with the patient in the supine position was used for drainage, debridement,
and irrigation in 6 patients with septic coxarthrosis. Continuous postoperative
intra-articular irrigation was not provided, nor were postoperative
decompression drains used. All patients were treated with intravenous
antibiotics for 3 weeks, followed by oral antibiotics for an additional minimum
of 3 weeks. Patients were followed for 6 to 42 months. Staphylococcus aureus was
identified in 4 of the 6 patients. All patients had a rapid postoperative
recovery. Mean Harris Hip Score at the last review was 97.5 points. All patients
showed full range of motion of the affected hip. No complications occurred with
this group of patients. Thus, 3-directional arthroscopic surgery combined with
large-volume irrigation is an effective treatment modality in cases of septic
arthritis of the hip. It is less invasive than arthrotomy and offers low rates
of postsurgical morbidity.
-----
Int Orthop. 2006 Aug 2; [Epub ahead of print]
Unicompartmental versus computer-assisted total knee replacement
for medial compartment knee arthritis: a matched paired study.
Manzotti A, Confalonieri N, Pullen C.
Ist Orthopaedic Department, Centro Traumatologico ed Ortopedico (C.T.O.) - I.C.P.,
Via Bignami 1, Milan, Italy.
Patients older than 60 with unicompartmental knee arthritis can be treated with
total or unicompartmental knee replacement. The aim of this study was to compare
the results of matched paired groups of patients with isolated medial
compartment knee arthritis replaced with either UKR (group A) or
computer-assisted TKR (group B). The results included 68 knees at a minimum
follow-up of 3 years. All patients had a varus deformity no greater than 8
masculine and a BMI lower than 30. Patients were matched in terms of
preoperative arthritis severity, age, gender and preoperative range of motion.
In the computer-assisted TKR group, all the implants were positioned within 4
masculine of the correct hip-knee-ankle angle and frontal tibial component
angle. The surgical time and hospital stay were statistically longer in the CA
TKR group. During the study no implant required revision. The results showed
higher scores for a UKR in the treatment of isolated primary unicompartmental
knee arthritis in patients older than 60 compared to a computer-assisted TKR. In
this study a computer-assisted alignment system for TKR with optimal implant
positioning did not produce equivalent clinical results compared to a UKR, but
did increase the financial costs.
-----
J Bone Joint Surg Am. 2006 Aug;88(8):1849-60.
Patellofemoral arthritis.
Grelsamer RP, Stein DA.
Mount Sinai Medical School, 5 East 98th Street, Box 1188, New York, NY 10029.
RGrelsamer@aol.com.
The surgeon must determine whether patellofemoral arthritis is the primary
source of a patient's knee pain and whether the arthritis is truly
unicompartmental. An anteromedial osteotomy of the tibial tuberosity is most
effective when the arthritis is localized to the distallateral portion of the
patellofemoral compartment. It is least effective when there is global arthritis
of the patellofemoral articulation. Total knee arthroplasty is an effective
treatment for patellofemoral arthritis. Patellofemoral replacement can be
considered for selected patients. A major reason for poor results after
patellofemoral replacement and patellectomy procedures is the development of
femorotibial arthritis.
-----
J Bone Joint Surg Am. 2006 Aug;88(8):1817-25.
Minimum ten-year results of primary bipolar hip arthroplasty for
degenerative arthritis of the hip.
Pellegrini VD Jr, Heiges BA, Bixler B, Lehman EB, Davis CM 3rd.
Department of Orthopaedics, University of Maryland School of Medicine, 22 South
Greene Street, Suite S11B, Baltimore, MD 21201. vpellegrini@umoa.umm.edu.
BACKGROUND: Bipolar hip arthroplasty has been advocated by some as an
alternative to total hip arthroplasty for the treatment of degenerative
arthritis of the hip. We sought to assess the results of this procedure at our
institution after a minimum duration of follow-up of ten years. METHODS: We
retrospectively reviewed a consecutive series of 152 patients (173 hips) who
underwent primary bipolar hemiarthroplasty for the treatment of symptomatic
degenerative arthritis of the hip with a cementless femoral component between
1983 and 1987. Of the original cohort of 152 patients, ninety-two patients (104
hips) were available for clinical and radiographic review at a mean of 12.2
years postoperatively. At the time of the latest follow-up, self-administered
Harris hip questionnaires were used to assess pain, mobility, activity level,
and overall satisfaction with the procedure. Biplanar hip radiographs were made
to evaluate bipolar shell migration, osteolysis, and femoral stem fixation.
RESULTS: At the time of the latest follow-up, nineteen patients (nineteen hips)
had undergone revision to total hip arthroplasty because of mechanical failure,
and three patients (three hips) were awaiting revision because of symptomatic
radiographic mechanical failure. Twelve acetabular revisions were performed or
scheduled for the treatment of pelvic osteolysis or protrusio acetabuli
secondary to component migration. Acetabular reconstruction required
bone-grafting, an oversized shell, and/or a pelvic reconstruction ring. The
overall rate of mechanical failure was 21.2% (twenty-two of 104 hips), with 91%
(twenty) of the twenty-two failures involving the acetabular component. Reaming
of the acetabulum at the time of the index arthroplasty was associated with a
6.4-fold greater risk of revision. The rate of implant survival, with revision
because of mechanical failure as the end point, was 94.2% for femoral components
and 80.8% for acetabular components at a mean of 12.2 years. Of the remaining
sixty-nine patients (eighty-one hips) in whom the original prosthesis was
retained, seventeeen patients (24.6%) rated the pain as moderate to severe.
Nearly 30% of patients with an intact prosthesis required analgesics on a
regular basis. Radiographs were available for fifty-eight hips (including all of
the hips with moderate to severe pain) after a minimum duration of follow-up of
ten years; twenty-eight of these fifty-eight hips had radiographic evidence of
acetabular component migration. CONCLUSIONS: This bipolar cup, when used for
hemiarthroplasty in patients with symptomatic arthritis of the hip, was
associated with unacceptably high rates of pain, migration, osteolysis, and the
need for revision to total hip arthroplasty, especially when the acetabulum had
been reamed. To the extent that these findings can be generalized to similar
implant designs with conventional polyethylene, we do not recommend bipolar
hemiarthroplasty as the primary operative treatment for degenerative arthritis
of the hip. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions to Authors
for a complete description of levels of evidence.
-----
J Natl Med Assoc. 2006 Jul;98(7):1126-35.
Safe pharmacologic treatment strategies for osteoarthritis pain
in African Americans with hypertension, and renal and cardiac disease.
Johnson J, Weinryb J.
Division of Geriatric Medicine, University of Pennsylvania, Philadelphia, PA
19104, USA. jcjohnson@mail.med.upenn.edu
Arthritis is the leading cause of disability in the United States.
Osteoarthritis, the most common form of arthritis, is a degenerative joint
disease affecting both whites and African Americans similarly. African Americans
have a high incidence rate of comorbidities, including hypertension,
cardiovascular disease (CVD) risk factors and diabetes. Treatment of
osteoarthritic pain in patients with comorbidities is often complicated by
potential safety concerns. Traditional nonsteroidal antiinflammatory drugs (NSAIDs)
and cyclooxygenase 2 (COX-2) specific NSAIDs have been shown to increase blood
pressure in hypertensive patients taking antihypertensive medications. Patients
with CVD risk factors taking low-dose aspirin for secondary prevention may be at
increased risk for gastrointestinal bleeding with NSAIDs. Diabetics face an
increased risk of renal complications. Because NSAIDs are associated with
adverse renal effects, they should be used cautiously in patients with advanced
renal disease. Acetaminophen is the most appropriate initial analgesic for
African Americans with chronic osteoarthritic pain and concurrent hypertension,
CVD risk factors or diabetes, and is recommended by the American College of
Rheumatology as first-line treatment. Many of the adverse effects commonly
associated with NSAIDs are not associated with acetaminophen. Safety concerns
surrounding pharmacologic treatment of osteoarthritis in African Americans are
reviewed.
-----
Am Fam Physician. 2006 Jul 15;74(2):293-300.
Chronic musculoskeletal pain in children: part II. Rheumatic
causes.
Junnila JL, Cartwright VW.
Army Medical Department Center and School, San Antonio, Texas, USA.
Jennifer.Junnila@us.army.mil
Primary care physicians should have a working knowledge of rheumatic diseases of
childhood that manifest primarily as musculoskeletal pain. Children with
juvenile rheumatoid arthritis can present with painless joint inflammation and
may have normal results on rheumatologic tests. Significant morbidity may result
from associated painless uveitis, and children with juvenile rheumatoid
arthritis should be screened by an ophthalmologist. The spondyloarthropathies
(including juvenile ankylosing spondylitis and reactive arthritis) often cause
enthesitis, and patients typically have positive results on a human leukocyte
antigen B27 test and negative results on an antinuclear antibody test. Patients
with acute rheumatic fever present with migratory arthritis two to three weeks
after having untreated group A beta-hemolytic streptococcal pharyngitis.
Henoch-Schbnlein purpura may manifest as arthritis before the classic purpuric
rash appears. Systemic lupus erythematosus is rare in childhood but may cause
significant morbidity and mortality if not treated early. Nonsteroidal
anti-inflammatory drugs and physical therapy may be useful early interventions
if a rheumatic illness is suspected. Family physicians should refer children
when the diagnosis is in question or subspecialty treatment is required. Part I
of this series discusses an approach to diagnosis with judicious use of
laboratory and radiologic testing.
-----
Rev Med Liege. 2006 May-Jun;61(5-6):334-40.
[Psoriasis and psoriatic arthritis]
[Article in French]
Henno A, Rausin A, Malaise M, de la Brassinne M.
Service de Dermatologie, CHU Sart Tilman, Liege,. Belgique. MDELABRASSINNE@chu.ulg.ac.be
Psoriasis is a frequent multifactorial chronic skin disease that can lead to a
decreased quality of life. Some patients also present arthritis. Those two
complex inflammatory diseases share some of their characteristics, but several
clinical manifestations can be distinguished in each of them. In addition to
classical medications (constituted of topical treatments, methotrexate,
ciclosporin and retinoids for cutaneous psoriasis and non steroidal
anti-inflammatory drugs or methotrexate for psoriatic arthritis), they are the
target of a new generation of therapies: the biologics.
-----
Mod Rheumatol. 2006;16(4):214-9.
Acceptability and usefulness of mizoribine in the management of
rheumatoid arthritis in methotrexate-refractory patients and elderly patients,
based on analysis of data from a large-scale observational cohort study.
Tanaka E, Inoue E, Kawaguchi Y, Tomatsu T, Yamanaka H, Hara M, Kamatani N.
Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho,
Shinjuku-ku, Tokyo, 162-0054, Japan, kamatani@ior.twmu.ac.jp.
This report documents the results of a study performed to examine clinical use
of mizoribine (MZR), using data from a large-scale prospective cohort study,
IORRA (Institute of Rheumatology Rheumatoid Arthritis). The number of patients
with RA entered in this study from October 2000 through October 2003 was 6238.
Three hundred and six patients (4.9%) received MZR therapy. Mizoribine users who
were taking methotrexate (MTX) (MTX-MZR group, n = 94) and over 70 years of age
(elderly group, n = 45) were collected. Cumulative retention rates of MZR were
calculated by Kaplan-Meier analysis. Median drug survival of MZR was 28 months
for the poor responders to MTX and 43 months for the poor responders to MZR,
with no significant difference between these groups. Cumulative retention rate
of MZR in the elderly group did not show a significant difference compared to
that in patients aged under 70 years. Ten patients (10.6%) in the MTX-MZR group
and 10 patients (22.2%) in the elderly group experienced adverse effects of MZR.
None of these adverse effects was serious. This study indicated that, although
MZR has not been frequently prescribed for RA patients, it may be useful and
relatively safe for patients who are poor responders to MTX as an additional
regimen to MTX therapy as well as for elderly patients.
-----
Ann Rheum Dis. 2006 Apr 10; [Epub ahead of print]
Double-blind comparison of Etanercept and Sulphasalazine, alone
and combined, in patients with active rheumatoid arthritis despite receiving
Sulphasalazine.
Combe BG, Codreanu C, Fiocco U, Gaubitz M, Geusens PP, Kvien TK, Pavelka K,
Sambrook PN, Smolen J, Wajdula J, Fatenejad S.
CHU Lapeyronie, France.
OBJECTIVE: To compare efficacy and safety of etanercept and sulphasalazine,
alone and in combination, in patients with active rheumatoid arthritis (RA)
despite sulphasalazine therapy. METHODS: A double-blind, randomised study in
adult patients with active RA despite stable sulphasalazine (2-3 g/day) therapy.
Primary endpoint was a 20% response by the American College of Rheumatology
criteria at 24 weeks. RESULTS: At baseline, the 3 treatment groups (sulphasalazine:
50, etanercept: 103, etanercept + sulphasalazine: 101 patients) were comparable
for demographic variables and disease activity. Lack of efficacy was the primary
reason for discontinuation (sulphasalazine: 12, etanercept: 1, etanercept +
sulphasalazine: 4; p<0.001). Significantly more patients receiving etanercept,
alone or in combination (74% for each) achieved ACR 20 responses at 24 weeks
compared with sulphasalazine (28%; p<0.01). Similarly, more patients in the
etanercept groups achieved ACR 50 and 70 responses compared with the
sulphasalazine group (p<0.01). In the groups receiving etanercept, significant
differences in the ACR core components were observed by week 2 compared with
sulphasalazine alone (p<0.01). The incidences of several common adverse events
(headache, nausea, asthenia) were lower with etanercept alone than with the
combination (p<0.05); infections and injection site reactions were higher with
etanercept alone (p<0.05). The safety profiles of both etanercept treatment
groups were comparable with previous etanercept experience. CONCLUSIONS: For all
efficacy variables assessed, etanercept alone or combined with sulphasalazine
resulted in substantial and similar improvement in disease activity from
baseline to week 24, compared with sulphasalazine alone in patients with active
RA despite sulphasalazine therapy. All 3 treatments were generally well
tolerated.
-----
Rheumatology (Oxford). 2006 Apr 7; [Epub ahead of print]
Safety of anti-TNF-{alpha} therapy in rheumatoid arthritis and
spondylarthropathies with concurrent B or C chronic hepatitis.
Roux CH, Brocq O, Breuil V, Albert C, Euller-Ziegler L.
Rheumatology Department, University Hospital, Nice, France.
Objective. To assess the safety of anti-tumour necrosis factor (TNF)-alpha
therapy in patients with rheumatoid arthritis (RA) or spondylarthropathies (SA)
and concurrent chronic hepatitis B or C.Methods. Records concerning 480
outpatients attending the Rheumatology Department of the University Hospital of
Nice (France) for RA or SA were retrospectively reviewed for the duration of
disease, treatment, serological status and biological data.Results. Six relevant
cases were identified: two of RA with chronic hepatitis B; one of SA with
chronic hepatitis B and three of RA with chronic hepatitis C. Five patients had
received etanercept and one infliximab; two had been given adalimumab after an
unsuccessful trial of etanercept. Patients with concurrent chronic hepatitis B
were also given lamivudine. In none of the cases had changes in serum
aminotransferases or viral load been reported.Conclusion. The use of anti-TNF-alpha
therapy (plus lamivudine in the presence of concurrent underlying hepatitis B
viral infection) appeared to be safe in that it had no effect on serum
aminotransferases and/or viral load. However, repeated monitoring is necessary
throughout the treatment period.
-----
J Rheumatol. 2006 Apr 1; [Epub ahead of print]
A Phase I Study Assessing the Safety, Clinical Response, and
Pharmacokinetics of an Experimental Infliximab Formulation for Subcutaneous or
Intramuscular Administration in Patients with Rheumatoid Arthritis.
Westhovens R, Houssiau F, Joly J, Everitt DE, Bouman-Thio E, Zhu Y, Sisco D, Van
Hartingsveldt B, Mascelli MA, Graham MA, Durez P.
OBJECTIVE: To assess safety, clinical response, and pharmacokinetics of
subcutaneous (SC) and intramuscular (IM) doses of an experimental formulation of
infliximab [including experimental SC doses following administration of
commercially-formulated intravenous (IV) infliximab] in patients with rheumatoid
arthritis (RA) refractory to methotrexate. METHODS: In this randomized,
open-label, 3-stage design, 43 subjects were enrolled in 7 dose groups. In Stage
I, 15 subjects received single SC doses of 0.5, 1.5, or 3.0 mg/kg. In Stage II,
21 subjects received one of 3 regimens: 100 mg SC every 2 weeks (3 injections);
3 mg/kg commercially-formulated IV infliximab every 2 weeks (2 infusions)
followed by 100 mg SC every 2 weeks (3 injections); or 100 mg IM every 2 weeks
(3 injections). In Stage III, 7 subjects received 100 mg SC every 4 weeks (3
injections). RESULTS: No treatment-related serious adverse events were observed,
and there were no serious injection site reactions. A low-titer infliximab
antibody response was detected in 27% of subjects receiving single SC doses, 5%
receiving multiple SC doses, and 43% receiving IM doses. SC administration
yielded roughly dose-proportional increases in Cmax and AUC. American College of
Rheumatology 20% response (ACR20) was achieved 2 weeks after the last injection
by 86.7% of subjects receiving single SC doses, 85.7% receiving SC doses every 2
weeks, 85.7% receiving both IV and SC doses, 57.1% receiving multiple IM doses,
and 80.0% receiving SC doses every 4 weeks. CONCLUSION: SC and IM treatment with
this experimental infliximab formulation was well tolerated and was associated
with a favorable ACR response.
-----
J Rheumatol. 2006 Apr 1; [Epub ahead of print]
Evaluation of the Comparative Efficacy and Tolerability of
Rofecoxib and Naproxen in Children and Adolescents with Juvenile Rheumatoid
Arthritis: A 12-Week Randomized Controlled Clinical Trial with a 52-Week
Open-Label Extension.
Reiff A, Lovell DJ, Van Adelsberg J, Kiss MH, Goodman S, Zavaler MF, Chen PY,
Bolognese JA, Cavanaugh PF Jr, Reicin AS, Giannini EH.
OBJECTIVE: To compare the safety and efficacy of rofecoxib* to naproxen for the
treatment of juvenile rheumatoid arthritis (JRA). METHODS: This was a 12-week,
multicenter, randomized, double-blind, double-dummy, active
comparator-controlled, non-inferiority study with a prespecified 52-week
open-label active comparator-controlled extension. Children (ages 2-11 yrs) and
adolescents (ages 12-17 yrs) received lower-dose (LD)-rofecoxib [0.3 mg/kg/day
up to 12.5 mg/day (base study only)]; or higher-dose (HD)-rofecoxib (0.6
mg/kg/day up to 25 mg/day) or naproxen 15 mg/kg/day as oral suspensions.
Adolescents received daily rofecoxib (LD) 12.5 (base study only) or (HD) 25 mg,
or naproxen 15 mg/kg/day (maximum 1000 mg/day) as tablets. The primary endpoint
was the time-weighted average proportion of patients meeting the American
College of Rheumatology Pediatric-30 (ACR Pedi 30) response criteria. A
prespecified bound for the 95% confidence interval for the ratio of the
percentage of ACR Pedi 30 responders was used to assess non-inferiority of
treatment response between groups. Safety was assessed throughout the study.
RESULTS: A total of 310 patients ages 2-17 years (181 (3/4) age 11) were
randomized to receive LD-rofecoxib (N = 109), HD-rofecoxib (N = 100), or
naproxen (N = 101). The ACR Pedi 30 response rates following 12 weeks of
treatment were 46.2%, 54.5%, and 55.1%, respectively. The relative rates of
response compared to naproxen were 0.81 (95% CI 0.61, 1.07) and 0.98 (95% CI
0.76, 1.26) for LD- and HD-rofecoxib, respectively. Both rofecoxib doses were
not inferior to naproxen. Patients (N = 227) entering the extension received HD-rofecoxib
or naproxen with efficacy maintained during the extension. All treatments were
generally well tolerated throughout the study. CONCLUSION: Daily treatment of
JRA patients with rofecoxib up to 12.5 or 25 mg was well tolerated, providing
sustained clinical effectiveness comparable to naproxen 15 mg/kg. *On September
30, 2004, Merck & Co., Inc. announced the voluntary worldwide withdrawal of
rofecoxib from the market.
-----
Rev Med Suisse. 2006 Mar 15;2(57):721-2, 725-6.
[Reactive arthritis]
[Article in French]
Revaz S, Dudler J.
Service de rhumatologie, medecine physique et rehabilitation, CHUV, 1011
Lausanne. Sylvie.Revaz@chuv.ch
Reactive arthritis is a disease closely related to the presence of the HLA-B27
antigen and characterized by sterile joint inflammation secondary to infection.
Arthritis is only one of the clinical manifestations of this systemic disease.
Its diagnosis rests on history, clinical examination and various serologies. The
prognosis is generally good, but recurrences are frequent, in particular in
HLA-B27 positive patients. Treatment is mainly symptomatic, and antibiotics
should be prescribed only in the event of an active infection. A 3 months course
of antibiotics could be beneficial on the long-term evolution in HLA-B27
positive patients, but this practice deserves to be confirmed by additional
randomized controlled studies.
-----
Rev Med Suisse. 2006 Mar 15;2(57):702-4, 707-8.
[Septic arthritis]
[Article in French]
Sadowski CM, Gabay C.
Service de rhumatologie, HUG, Clinique Beau-Sejour, 1211 Geneve 14.
carole.medinger@hcuge.ch
Septic arthritis is a medical emergency that may be associated with significant
mortality (10-15%) and morbidity (25-50%), in case of delayed management. When
septic arthritis is suspected, arthrocentesis and culture of the synovial fluid
are the gold standard. The absence of fever, rigors, leukocytosis or elevated
erythrocyte sedimentation rate does not exclude the diagnosis of septic
arthritis. Age, chronic arthropathy, or arthroplasty are particularly associated
with increased morbidity. Therapy consists in antibiotics, joint immobilisation
(maximum 3 days) and medical drainage, in case of persisting joint effusion.
-----
Am J Orthop. 2006 Feb;35(2):67-73.
Orthopedic surgical management of hip and knee involvement in
patients with juvenile rheumatoid arthritis.
Iesaka K, Kubiak EN, Bong MR, Su ET, Di Cesare PE.
Musculoskeletal Research Center, NYU-Hospital for Joint Diseases, New York, NY,
USA.
Juvenile rheumatoid arthritis is the most common arthritic disease of childhood
and a leading cause of childhood disability, affecting an estimated 300,000 US
children and adolescents aged < or =16 years. Approximately 10% to 30% of
patients experience functional deficits resulting from both the articular and
systemic manifestations of their disease, including leg length inequality and
deformity, that are often more crippling than joint destruction. Surgical
intervention to treat bone and soft-tissue deformity, leg length inequality, and
joint destruction is indicated when medical therapy has failed. Synovectomy,
soft-tissue release, osteotomy, and epiphysiodesis are used to treat deformity
and early joint destruction. Arthroplasty remains the primary therapy for joint
destruction, although it is fraught with complications specific to this young
patient population.
-----
Expert Opin Pharmacother. 2006 Jan;7(1):91-8.
Tacrolimus in rheumatoid arthritis.
Fleischmann R, Iqbal I, Stern RL.
University of Texas Southwestern Medical Centre at Dallas, USA. royfleischmann@radiantresearch.com
Tacrolimus is an immunosuppressive drug that has been used widely in organ
transplantation and topically for atopic dermatitis. Tacrolimus exerts its
immunosuppressive effects by the inhibition of calcineurin, leading to
interference with T-cell activation. As T-cell activation plays a major role in
the pathogenesis of rheumatoid arthritis, there has been an interest in the use
of tacrolimus for the treatment of rheumatoid arthritis. The pharmacological
properties of tacrolimus have the potential of suppressing the production of
inflammatory cytokines, improvement of joint inflammation, improvement of bone
and cartilage destruction, improvement of functional status and relief from
arthritic pain. This article reviews the pharmacodynamics, pharmacokinetics,
clinical efficacy, safety and role of tacrolimus in the treatment of rheumatoid
arthritis.
-----
Clin Infect Dis. 2006 Jan 15;42(2):216-23. Epub 2005 Dec 6.
Outcome of prosthetic joint infection in patients with rheumatoid
arthritis: the impact of medical and surgical therapy in 200 episodes.
Berbari EF, Osmon DR, Duffy MC, Harmssen RN, Mandrekar JN, Hanssen AD,
Steckelberg JM.
Mayo Clinic College of Medicine, Rochester, MN, USA. berbari.elie@mayo.edu
BACKGROUND: Prosthetic joint infection in patients with rheumatoid arthritis is
a serious complication of total joint arthroplasty. Little information is
available on the outcome of medical and surgical treatments of prosthetic joint
infection in patients with rheumatoid arthritis. METHODS: We conducted a
retrospective analysis of all patients with rheumatoid arthritis and a total hip
or total knee arthroplasty infection evaluated at Mayo Clinic (Rochester, MN)
between 1 January 1969 and 31 December 1995. RESULTS: A total of 200 first
episodes of prosthetic joint infection in 160 patients with rheumatoid arthritis
were diagnosed during the study period. Thirty-seven percent of prosthetic joint
infection episodes were due to Staphylococcus aureus. Of these episodes, 23% and
19% were treated with debridement and retention of components and 2-stage
exchange, respectively. The type of surgical procedure was the only analyzed
clinical variable that was associated with treatment failure (P < .001). Rates
of 5-year survival free of treatment failure for patients with prosthetic joint
infection episodes treated with debridement and retention of components, 2-stage
exchange, and resection arthroplasty were 32% (95% confidence interval [CI],
21%-49%), 79% (95% CI, 66%-93%), and 61% (95% CI, 49%-74%), respectively.
CONCLUSIONS: S. aureus is the most common pathogen among patients with
rheumatoid arthritis with prosthetic joint infection. Two-stage exchange was
used in only 19% of the prosthetic joint infection episodes among patients with
rheumatoid arthritis during the study period, but it was associated with the
best outcome. The variable most strongly associated with the outcome was the
type of surgical procedure.
-----
Int Orthop. 2005 Dec 22;:1-6 [Epub ahead of print]
Multi directional intertrochanteric osteotomy for primary and
secondary osteoarthritis-results after 15 to 29 years.
Haverkamp D, Eijer H, Patt TW, Marti RK.
Department of Orthopaedic Surgery, Academic Medical Centre, Meibergdreef 15,
1105 AZ, Amsterdam, The Netherlands, info@osteotomie.nl.
Between 1974 and 1987, 276 intertrochanteric osteotomies were performed in 217
patients. In 48 hips the osteotomy was done for idiopathic osteoarthritis. In
166 hips the osteoarthritis was secondary to acetabular dysplasia, in 23 to
trauma, in 14 to slipped capital femoral epiphysis, in five to Legg-Calve-Perthes'
disease and in 20 to avascular necrosis of the femoral head. Good results were
achieved in young females with mild osteoarthritis secondary to acetabular
dysplasia, and in patients with posttraumatic osteoarthritis. All other
indications showed a poorer long-term survival. Our study shows that acetabular
dysplasia and posttraumatic arthritis remain valid indications for
intertrochanteric osteotomy.
-----
Clin Rheumatol. 2005 Dec 20;:1-7 [Epub ahead of print]
Disease activity and functional changes of RA patients receiving
different DMARDs in clinical practice.
Osiri M, Deesomchok U, Tugwell P.
Division of Rheumatology, Department of Medicine, Faculty of Medicine,
Chulalongkorn University, Rama IV Road, Pathumwan, Bangkok, 10330, Thailand,
Manathip.O@chula.ac.th.
The aim of this study was to compare the effectiveness of different
disease-modifying anti-rheumatic drugs (DMARDs) in improving disease activity
and functional status in patients with rheumatoid arthritis (RA). One hundred
and fifty-two Thai RA patients treated with at least one DMARD were enrolled in
this 1-year cohort. Demographic characteristics, baseline and end-of-study data
on disease activity and Health Assessment Questionnaire (HAQ) Disability Index
of the subjects were compared among different DMARD options. Predictors of HAQ
score were investigated using regression analysis. The results showed that the
studied patients had established RA with mild to moderate activity. More than
85% were prescribed methotrexate (MTX) as single or combined DMARDs. At 1 year,
improvement in most activity measures was experienced. However, all patients had
functional declines. Patients taking antimalarial agents had the maximal rate of
functional deterioration. Patients taking MTX-based DMARDs had significantly
lower rate of functional decline than patients taking DMARDs without MTX
(p=0.018). Only patients receiving MTX-based DMARDs had clinically meaningful
improvement in HAQ score. The predictors of HAQ score at 1 year included
baseline HAQ score and patient global assessment at end of study. In conclusion,
although DMARD treatment was shown to improve disease activity in RA patients,
functional deterioration was evident in our cohort. Thus, measures of functional
status are more appropriate than measures of disease activity to evaluate
treatment effects of DMARDs in established RA in clinical practice. MTX-based
DMARDs should be prescribed where possible in RA patients with persisting
activity due to their ability to delay functional deterioration.
-----
J Rheumatol. 2005 Dec 15; [Epub ahead of print]
Etanercept in Combination with Sulfasalazine, Hydroxychloroquine,
or Gold in the Treatment of Rheumatoid Arthritis.
O'dell JR, Petersen K, Leff R, Palmer W, Schned E, Blakely K, Haire C, Fernandez
A.
OBJECTIVE: To prospectively determine the efficacy and safety of etanercept in
combination with sulfasalazine (SSZ), hydroxychloroquine (HCQ), and gold in the
treatment of rheumatoid arthritis (RA). METHODS: A prospective open-label study
enrolled 119 patients with RA who had active disease despite stable therapy with
SSZ (n = 50), HCQ (n = 50), or intramuscular gold (n = 19). Primary efficacy
endpoints consisted of American College of Rheumatology responses at 24 and 48
weeks. Safety was established at regularly scheduled visits. RESULTS: Patients
in each etanercept combination showed significant improvement at both 24 and 48
weeks. Toxicity withdrawals by 48 weeks included gold (n = 1): proteinuria; HCQ
(n = 5): septic wrist and bilateral pneumonia, rash, optic neuritis, breast
cancer, squamous cancer of the tongue; and SSZ (n = 5): otitis media, elevated
liver function indicators, pericarditis, rash, and gastroenteritis. The most
common adverse events not requiring discontinuation from the study were
injection site reactions (43% of patients) and upper respiratory type infections
(34%). CONCLUSION: This study is the first to prospectively evaluate the safety
of etanercept in combination with SSZ, HCQ, and gold in patients with RA.
Etanercept in combination with SSZ, HCQ, or gold was efficacious and well
tolerated, with a discontinuation rate of 9% (11/119) for adverse events at 48
weeks.
-----
Ther Apher Dial. 2005 Dec;9(6):459-68.
Therapeutic apheresis-state of the art in the year 2005.
Bosch T.
Nephrology Division, Department of Internal Medicine I, University Hospital
Munich-Grosshadern, Munich, Germany.
Therapeutic apheresis is an extracorporeal blood purification method for the
treatment of diseases in which pathological proteins or cells have to be
eliminated. Selective plasma processing is more efficient in pathogen removal
than unselective plasma exchange and does not require a substitution fluid like
albumin. This overview presents the various selective devices for the treatment
of plasma (plasmapheresis) and blood cells (leukocyte apheresis). Prospective
randomized trials were performed for the treatment of age-related macular
degeneration (Rheopheresis), sudden hearing loss (heparin-induced lipoprotein
precipitation [HELP]), rheumatoid arthritis (Prosorba), dilative cardiomyopathy
(Ig-Therasorb, Immunosorba), acute-on-chronic liver failure (molecular adsorbent
recirculating system [MARS]), and ulcerative colitis (Cellsorba). Prospective
non-randomized controlled trials were carried out treating hypercholesterolemia
(Liposorber) and crossmatch-positive recipients before kidney transplantation (Immunosorba).
Uncontrolled studies were done for ABO-incompatibility in living donor kidney
transplantation (KT) (Glycosorb), acute humoral rejection after KT (Immunosorba)
and acute liver failure (Prometheus). According to the 2002 International
Apheresis Registry covering 11428 sessions in 811 patients, 79% of the patients
showed an improvement of their condition by apheresis and only a few sessions
were fraught with adverse effects (AE). The major AE were blood access
difficulties (3.1%) and hypotension (1.6%). In summary, therapeutic apheresis is
a safe and effective procedure for the treatment of diseases refractory to drug
therapy.
-----
J Rheumatol. 2005 Dec;32(12):2303-10.
A phase 2 dose-finding study of PEGylated recombinant methionyl
human soluble tumor necrosis factor type I in patients with rheumatoid
arthritis.
Furst DE, Fleischmann R, Kopp E, Schiff M, Edwards C 3rd, Solinger A, Macri M;
990136 Study Group.
Department of Rheumatology, University of California at Los Angeles, California
90095, USA. defurst@mednet.ucla.edu
OBJECTIVE: In a phase 2 study, to assess the efficacy and safety of pegsunercept,
a soluble tumor necrosis factor receptor type I, for the treatment of rheumatoid
arthritis (RA). METHODS: Patients were randomized to receive weekly subcutaneous
injections of placebo (n = 61) or active drug [400 microg/kg (n = 67) or 800
microg/kg (n = 66)] for 12 weeks. The primary efficacy endpoint was American
College of Rheumatology 20% response (ACR20) at Week 12. Secondary efficacy
measures included ACR50 and ACR70 responses, and changes in individual ACR
components at Week 12. Safety assessments included summaries of adverse events
including infectious episodes. RESULTS: Treatment with pegsunercept resulted in
a significantly higher ACR20 response at Week 12 in the 800 microg/kg group
(45%) compared with the placebo group (26%; p = 0.020). The treatment effect of
pegsunercept (both doses) over the study period showed statistically significant
improvement for most ACR components and health related quality of life, with the
800 microg/kg group showing greater clinical improvements in efficacy measures.
The overall incidence of adverse events and infectious episodes was similar
among the treatment and placebo groups. CONCLUSION: In this 12 week dose-finding
study of 194 patients, weekly subcutaneous dosing with pegsunercept showed
beneficial effects in improving the signs and symptoms of RA. It appeared to be
safe and well tolerated in this small number of patients. Significant clinical
improvements were seen in patients in the 800 microg/kg group; however, this
dose may be suboptimal, and further evaluation of this product with higher doses
or a more frequent dosing regimen is warranted.
-----
Oper Orthop Traumatol. 2005 Nov;17(6):569-578.
[Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in the
Perioperative Phase in Traumatology and Orthopedics Effects on Bone Healing.]
[Article in German]
Beck A, Salem K, Krischak G, Kinzl L, Bischoff M, Schmelz A.
Abteilung fur Unfallchirurgie, Hand- und Wiederherstellungschirurgie,
Universitatsklinikum Ulm, Steinhovelstrasse 9, D-89075, Ulm, alexander.beck@medizin.uni-ulm.de.
OBJECTIVE: To achieve analgesic, anti-inflammatory and antipyretic effects in
traumatology and orthopedic surgery without side effects or with the least
possible side effects, with special emphasis on bone healing. INDICATIONS: Acute
and chronic inflammatory conditions, e. g., rheumatoid arthritis, ankylosing
spondylitis. Degenerative joint disease. Posttraumatic and postoperative pain,
edema, or fever. Prevention of heterotopic bone formation. CONTRAINDICATIONS:
Hypersensitivity. Gastrointestinal ulceration or bleeding. Severe hepatic or
renal impairment. RESULTS: Nonsteroidal anti-inflammatory drugs (NSAIDs) are
invaluable in treating a variety of musculoskeletal conditions. As well as their
excellent analgesic potency their anti-inflammatory effects are beneficial in
treating posttraumatic and postoperative edema. In addition, NSAIDs inhibit
heterotopic bone formation after hip arthroplasty. Animal studies, however, have
demonstrated that they cause delayed fracture healing. Although clinical studies
have not yet supplied unequivocal evidence of this effect in human subjects, the
authors recommend that in the presence of other risk factors which may adversely
affect fracture healing, such as smoking, diabetes mellitus or peripheral
arterial occlusive disease, the indication of NSAID use for analgesia should be
strictly limited. Therapeutic alternatives such as centrally acting agents (e.
g., weak opioids) should be considered in these patients.
-----
J Hand Surg [Am]. 2005 Nov;30(6):1282-7.
Long-term results of silicone wrist arthroplasty in patients with
rheumatoid arthritis.
Kistler U, Weiss AP, Simmen BR, Herren DB.
Department of Hand Surgery, Schulthess Clinic, Zurich, Switzerland.
PURPOSE: The surgical treatment of the rheumatoid wrist is key in managing the
affected hand. Wrist fusion is often the treatment of choice in cases of severe
destruction and deformation although most patients would prefer a
motion-preserving procedure. The implantation of a wrist prosthesis might be an
alternative to partial arthrodesis for selected cases. In this series we
analyzed the long-term results (minimum follow-up period, 10 y) of the Swanson
silicone spacer for the wrist in patients with rheumatoid arthritis. METHODS:
Sixteen patients with rheumatoid arthritis with 18 silicone spacers for the
wrists were reviewed after a minimum follow-up period of 10 years (average, 15
y). Subjective evaluation, clinical examination, and radiographic analysis were
included. An additional 9 patients (9 wrists) were interviewed by telephone.
RESULTS: In 12 of the patients the subjective result was good or very good,
mostly because of adequate pain relief. The average range of motion for flexion
(average, 28 degrees )/extension (average, 15 degrees ) was 43 degrees with a
wide variation within the series. Radiologically all wrists had diminished
residual carpal height at follow-up evaluation and 9 of the wrists had evidence
of osteolysis and foreign-body granuloma. The initial good correction of the
ulnar translation of the wrist was lost partially in the follow-up period (1.1
vs 4.0 mm). Three of the patients needed surgical revision within the follow-up
period; all were converted to wrist fusion. CONCLUSIONS: These long-term results
suggest that the silicone wrist spacer still may be considered as an alternative
to wrist fusion or more complex wrist joint prostheses in patients with
rheumatoid arthritis, especially in severe cases and in patients with low
demands. In the long term osteolysis caused by foreign-body granulation is to be
expected and has to be considered. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic,
Level IV.
-----
J Hand Surg [Am]. 2005 Nov;30(6):1276-81.
Comparison of swanson and sutter metacarpophalangeal
arthroplasties in patients with rheumatoid arthritis: a prospective and
randomized trial.
Parkkila T, Belt EA, Hakala M, Kautiainen H, Leppilahti J.
Rheumatism Foundation Hospital, Heinola, FinlandDepartment of Surgery, Oulu
University Hospital, Oulu, Finland; Department of Surgery, Oulu University
Hospital, Oulu, Finland.
PURPOSE: To perform a prospective and randomized comparison of the clinical
outcome of patients with rheumatoid arthritis who had Swanson or Sutter implant
replacement arthroplasty of the metacarpophalangeal joints. METHODS: There were
45 patients (3 men, 42 women) and 49 hands; a total of 75 Swanson and 99 Sutter
implants were inserted. The mean time between surgery and the final follow-up
control visit was 58 months (range, 37-80 mo). Preoperative and postoperative
measurements were performed including active extension and flexion, correction
of ulnar deviation, and strength. RESULTS: There was no statistically
significant difference between groups with regard to active extension deficit
correction. Mean active flexion decreased less in the Sutter group than in the
Swanson group but difference between the groups was statistically significant in
only the index finger. At the final follow-up examination no significant
differences existed between the groups in the correction of ulnar deviation or
arc of motion. Grip strengths, chuck pinch, and thump-to-fingertip grip
strengths did not improve in either of the groups. CONCLUSIONS: In this study
clinical results showed no significant difference between the groups with the
single exception of the amount of index finger metacarpophalangeal joint
flexion. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level II.
-----
Semin Arthritis Rheum. 2005 Oct;35(2):77-94.
Diet and rheumatoid arthritis: a review of the literature.
Stamp LK, James MJ, Cleland LG.
Department of Medicine, Christchurch School of Medicine and Health Sciences,
University of Otago, New Zealand.
INTRODUCTION: Rheumatoid arthritis is a common inflammatory condition. A large
number of patients seek alternative or complementary therapies of which diet is
an important component. This article reviews the evidence for diet in rheumatoid
arthritis along with the associated concept of oral tolerization. METHODS:
References were taken from Medline from 1966 to September 2004. The keywords,
rheumatoid arthritis, diet, n-3 fatty acids, vitamins, and oral tolerization,
were used. RESULTS: Randomized controlled trials (RCTs) indicate that dietary
supplementation with n-3 fatty acids provides modest symptomatic benefit in
groups of patients with rheumatoid arthritis. Epidemiological studies and RCTs
show cardiovascular benefits in the broader population and patients with
ischemic heart disease. A number of mechanisms through which n-3 fats may reduce
inflammation have been identified. In a small number of patients with rheumatoid
arthritis, other dietary manipulation such as fasting, vegan, and elimination
diets may have some benefit. However, many of these diets are impractical or
difficult to sustain long term. CONCLUSIONS: Dietary manipulation provides a
means by which patients can a regain a sense of control over their disease.
Dietary n-3 supplementation is practical and can be easily achieved with
encapsulated or, less expensively, bottled fish oil.
-----
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005 Oct;100(4):433-40.
The long-term effect of anti TNF-alpha treatment on
temporomandibular joints, oral mucosa, and salivary flow in patients with active
rheumatoid arthritis: A pilot study.
Moen K, Kvalvik AG, Hellem S, Jonsson R, Brun JG.
Broegelmann Research Laboratory, The Gade Institute, University of Bergen,
Norway; Student, Department of Oral and Maxillofacial Surgery, Haukeland
University Hospital, Bergen, Norway.
OBJECTIVE: The objective of this study was to evaluate the long-term effects of
anti-TNF-alpha treatment on temporomandibular joints (TMJs), oral mucosa, and
salivary flow in RA. STUDY DESIGN: Seventeen patients received infusions of TNF-alpha
blocking agents after 0, 2, and 6 weeks, and then every 8 weeks until week 54
(follow-up). Clinical dysfunction index (D(i)) for the TMJ system, salivary
flow, disease activity score (DAS28), and other medical assessments were
calculated at weeks 0 and 54. RESULTS: Median D(i) was 5.0 (range 0-21) at
baseline and 1.0 (range 0-6) (P=.001) at follow-up. Mean salivary flow was 3.2
mL/15 minutes at baseline and 4.6 at follow-up (P=.055). Two (11.7%) of the
patients developed oral candidiasis during the period of treatment. The median
DAS28 was 6.2 (range, 4.7-7.7) at baseline and 4.1 (range, 1.6-6.8) at follow-up
(P=.001). CONCLUSION: We conclude that anti-TNF-alpha blocking treatments have
beneficial effects on oral as well as general manifestations of RA.
-----
J Shoulder Elbow Surg. 2005 Sep-Oct;14(5):485-91.
Outcome of Copeland surface replacement shoulder arthroplasty.
Thomas SR, Wilson AJ, Chambler A, Harding I, Thomas M.
Wexham Park Hospital, Windsor, United Kingdom.; Heatherwood Hospital, Windsor,
United Kingdom.
We report the outcome of humeral head surface replacement hemiarthroplasty
performed at our institution using the Copeland prosthesis. We followed 56
shoulders (52 patients) for a mean of 34.2 months (range, 24-63 months). Two
were lost to follow-up, and there were six deaths unrelated to the shoulder
surgery. Preoperative diagnoses in the remainder were osteoarthritis (20),
rheumatoid arthritis (26), rotator cuff tear arthropathy (1), and post-traumatic
arthrosis (1). The mean age was 68 years. Constant scores for the whole group
improved from a mean preoperative score of 16.4 (range, 8-36) to 54.0 (range,
20-83) at last follow-up (P < .05). Three cases underwent subsequent
arthroscopic subacromial decompression for impingement symptoms. One case
required revision for aseptic loosening to a stemmed implant. Contained,
nonprogressive osteolysis was seen in 2 cases. One periprosthetic humeral neck
fracture was managed successfully nonoperatively. These results are comparable
to those obtained with a modern stemmed hemiarthroplasty and are similar to
Copeland's own series.
-----
J Shoulder Elbow Surg. 2005 Sep-Oct;14(5):471-9.
Total shoulder arthroplasty: Long-term survivorship, functional
outcome, and quality of life.
Deshmukh AV, Koris M, Zurakowski D, Thornhill TS.
Department of Orthopaedics, Kaiser West Los Angeles Medical Center, Los Angeles,
CA, USA.
This study examines long-term outcomes of total shoulder arthroplasty (TSA) via
survivorship analysis, patient questionnaires, and minimum 10-year physical
examinations. The study group consisted of 320 consecutive TSAs performed in 267
patients between 1974 and 1988. Diagnoses included rheumatoid arthritis (69%),
osteoarthritis (22%), and juvenile rheumatoid arthritis (4.7%). Minimum 10-year
physical examination follow-up was obtained on a subset of 72 TSAs at a mean
(+/- SD) of 14.0 +/- 2.7 years. A Disabilities of the Arm, Shoulder and Hand
(DASH) questionnaire was obtained from 80 patients with 103 TSAs at a mean of
15.4 +/- 3.4 years after the index procedure (range, 10.4-23.2 years).
Kaplan-Meier survivorship rates with revision as the endpoint at 5, 10, 15, and
20 years were 98%, 93%, 88%, and 85%, respectively. Of the shoulders, 22 (6.9%)
required a revision, most commonly for loosening of one or both components (15
shoulders). Dislocation occurred earlier than other causes of revision or
complication (P < .05, analysis of variance). Minimum 10-year physical
examination follow-up revealed lasting, significant improvements in range of
motion and strength. The patients' subjective assessments of TSA were favorable
in that 92% felt that their shoulder was "much better" or "better" after TSA.
The mean DASH score was 49 +/- 25; no significant differences were found among
diagnoses. Long-term analysis of the Neer-type TSA revealed survivorship rates
comparable to other joint replacements. The significant improvements in relief
of pain, shoulder range of motion, and strength are associated with a high
degree of patient satisfaction.
-----
J Hand Surg [Am]. 2005 Sep;30(5):932-6.
Health status after total wrist arthrodesis for posttraumatic
arthritis.
Adey L, Ring D, Jupiter JB.
Hand and Upper Extremity Service, Department of Orthopaedic Surgery,
Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA.
PURPOSE: Total wrist arthrodesis is regarded as the most predictable way to
relieve the pain of posttraumatic wrist arthritis. Wrist arthrodesis also is
believed to be compatible with a high level of upper-extremity function. This
study evaluated the effect of total wrist arthrodesis on both general and
upper-extremity-specific health status in patients treated for posttraumatic
wrist arthritis. METHODS: By using an institutional review board-approved
protocol 22 patients were evaluated an average of 6 years after total wrist
arthrodesis for posttraumatic arthritis. Upper-extremity-specific and general
health status were measured using the Disabilities of the Arm, Shoulder, and
Hand questionnaire and the Short-Form 36 (SF-36) instruments, respectively.
Patient satisfaction and interest in pursuing a wrist-mobilizing procedure
should one become available also were assessed. Objective assessment included
grip strength, digit range of motion, and radiographic fusion. RESULTS: Grip
strength averaged 79% of the uninvolved wrist. The average Disabilities of the
Arm, Shoulder, and Hand questionnaire score was 25. The average physical
component score of the Short-Form 36 was 39 and the average mental component
score was 52. Fourteen patients complained of wrist pain, including severe pain
in 4 patients. Fifteen patients were satisfied or very satisfied with the result
of the fusion, 5 patients were neutral, and 2 patients were mildly dissatisfied.
Twenty patients would elect to have a procedure that could make their wrist move
again if one were available. CONCLUSIONS: Substantial dysfunction was noted on
both upper-extremity-specific and general health status measures after total
wrist arthrodesis for posttraumatic conditions. Pain was improved but not
eliminated.
-----
Internist (Berl). 2005 Sep 30; [Epub ahead of print]
[Up-to-date antirheumatic therapy: Methotrexate vs. biologicals.]
[Article in German]
Sautner J, Leeb BF.
II. Medizinische Abteilung, Niederosterreichisches Kompetenzzentrum fur
Rheumatologie, Humanisklinikum NO - Stockerau, .
Rheumatoid arthritis potentially causes joint destruction, organ failures, and
accompanying disorders. Therefore initiating therapeutic measures as early as
possible is crucial, whereby symptomatic treatment only is definitely
insufficient. Among the traditional disease-modifying antirheumatic drugs (DMARD)
Methotrexate is regarded the gold standard. Increasing knowledge of
cell-interactions, particularly of the cytokine-cascade, resulted in new
therapeutic options. Direct impact via "biologicals" on key inflammatory
mediators, primarily TNF-alpha, offers the possibility of effectively modulating
or even arresting disease progression. Nowadays, those substances are applied in
non-responders to traditional DMARD. Despite their benefits, cons like an
increased risk for infections, for exacerbating latent tuberculosis and possibly
for malignancies must be considered. Thus, a thorough patient check-up before
initiating these therapies is mandatory. Pharmacoeconomic aspects influence the
discussion about these "new therapies". The high costs of biologicals, however,
should be related to the possible reduction of the disease's psychological,
social and economic burdens.
-----
Am Fam Physician. 2005 Sep 15;72(6):1037-47.
Diagnosis and management of rheumatoid arthritis.
Rindfleisch JA, Muller D.
Department of Family Medicine, University of Wisconsin-Madison, Madison,
Wisconsin, USA.
Rheumatoid arthritis is a chronic inflammatory disease characterized by
uncontrolled proliferation of synovial tissue and a wide array of multisystem
comorbidities. Prevalence is estimated to be 0.8 percent worldwide, with women
twice as likely to develop the disease as men. Untreated, 20 to 30 percent of
persons with rheumatoid arthritis become permanently work-disabled within two to
three years of diagnosis. Genetic and environmental factors play a role in
pathogenesis. Although laboratory testing and imaging studies can help confirm
the diagnosis and track disease progress, rheumatoid arthritis primarily is a
clinical diagnosis and no single laboratory test is diagnostic. Complications of
rheumatoid arthritis may begin to develop within months of presentation;
therefore, early referral to or consultation with a rheumatologist for
initiation of treatment with disease-modifying antirheumatic drugs is
recommended. Several promising new disease-modifying drugs recently have become
available, including leflunomide, tumor necrosis factor inhibitors, and anakinra.
Nonsteroidal anti-inflammatory drugs, corticosteroids, and nonpharmacologic
modalities also are useful. Patients who do not respond well to a single
disease-modifying drug may be candidates for combination therapy. Rheumatoid
arthritis is a lifelong disease, although patients can go into remission.
Physicians must be aware of common comorbidities. Progression of rheumatoid
arthritis is monitored according to American College of Rheumatology criteria
based on changes in specific symptoms and laboratory findings. Predictors of
poor outcomes in early stages of rheumatoid arthritis include low functional
score early in the disease, lower socioeconomic status, early involvement of
many joints, high erythrocyte sedimentation rate or C-reactive protein level at
disease onset, positive rheumatoid factor, and early radiologic changes.
-----
Orthopedics. 2005 Sep;28(9):943-4.
Surface replacement solutions for the arthritic hip.
Goldberg VM.
Department of Orthopedics, Case Western Reserve University, University Hospitals
of Cleveland, Cleveland, Ohio 44106, USA.
Surface replacement is a conservative treatment for young, active patients with
hip osteoarthritis. It provides an increased range of motion as the result of a
larger diameter head and improved wear characteristics because of the
metal-on-metal articulation as well as an extremely low dislocation rate and
increased patient function. While early results are encouraging, long-term
outcomes are necessary to define and delineate the role of surface replacement
arthroplasty in the treatment of significant hip arthritis.
-----
Acta Orthop. 2005 Aug;76(4):573-9.
Radiostereometric analysis of the double-coated STAR total ankle
prosthesis.
Carlsson A, Markusson P, Sundberg M.
Department of Orthopedics, Malmo University Hospital, SE-205 02, Malmo, Sweden.
Background The designs of total ankle prostheses have changed in recent years in
order to give better performance. Only a few studies of these ankle prostheses
have been published, however, and none on micromotion.Patients and methods We
evaluated 5 patients with rheumatoid arthritis and 5 with osteoarthosis, 4 (3-5)
yearsafter arthroplasty with the double-coated STAR prosthesis.Clinical
examination included AOFAS hindfoot score. Standardized a-p and lateral
radiographs were taken and RSA analyses were done at regular intervals.Results
There was no difference in results between ankles operated on due to rheumatoid
arthritis and due to osteoarthrosis. A rapid initial migration was observed for
the tibial components at 6 weeks, but thereafter all but 1 implant seemed
stable. The migration pattern for the talar component was similar.Rotation
around the 3 axes was observed for the tibial components at 6 weeks, but not
thereafter. The talar components became stable for rotation around the
longitudinal and sagittal axes, but not around the transverse axis. 8 out of 10
ankles were painless. The median total AOFAS score was 83 and the median range
of motion was 32 degrees . None of the 20 components had changed position and
there were no signs of bone resorption.Interpretation Provided the indication is
adequate and the prosthesis has been implanted correctly, the double-coated STAR
ankle prosthesis will have a satisfactory fixation to underlying bone.
-----
J Orthop Sports Phys Ther. 2005 Aug;35(8):502-20.
The unstable metacarpophalangeal joint in rheumatoid arthritis:
anatomy, pathomechanics, and physical rehabilitation considerations.
Bielefeld T, Neumann DA.
Physical Therapy Department, Zablocki VA Medical Center, Milwaukee, WI 53295,
USA. hand-pt@worldnet.att.net
The metacarpophalangeal (MCP) joints bestow important strength to the
longitudinal and transverse arch systems of the hand. In addition, these joints
guide active movements of the fingers in 2 degrees of freedom, while allowing
sufficient laxity for passive accessory motions. Both stability and mobility
functions are attained in the healthy hand by a complex interaction among the
muscles and the joints' periarticular connective tissues. Rheumatoid arthritis
(RA) often causes destruction of the MCP joints' connective tissues, which leads
to weakness of the tissues and an imbalance of active and passive forces, and
subsequently, instability, pain, and deformity. The 2 most common deformities of
the MCP joints associated with RA and instability are palmar subluxation and
ulnar "drift." Therapists and physicians often collaborate to treat these
conditions through a combination of surgical and nonsurgical interventions. Two
of the more conservative nonsurgical interventions typically involve a
combination of splinting and education on joint protection. Additional
nonsurgical treatment may include the judicious use of exercise and methods for
relieving pain and reducing inflammation. Surgical intervention is often
indicated when the more conservative treatments fail to arrest the progression
of the pain or deformity. Regardless of the specific approach, effective
intervention for instability of the MCP joint requires that the clinician
possess a sound knowledge of the anatomy and the pathomechanical influences that
predispose or cause the instability. This clinical commentary is intended to
provide this information, as well as offer treatment guidelines based on our
clinical experience. Whenever possible, research will be cited to support
clinical interventions. This paper is especially geared to the therapist who may
not currently specialize in the treatment of instability of the MCP joint but
may require basic information on this important topic.
-----
J Clin Pharmacol. 2005 Jul;45(7):751-62.
Rheumatoid arthritis: an overview of new and emerging therapies.
Doan T, Massarotti E.
750 Washington Street, NEMC 599, Boston, MA 02111.
Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune
disorder characterized by symmetric inflammation of synovial joints leading to
progressive erosion of cartilage and bone. The aim of treatment is to mitigate
joint destruction, preserve function, and prevent disability. The American
College of Rheumatology guidelines for the treatment of RA recommend that newly
diagnosed patients with RA begin treatment with disease-modifying antirheumatic
drugs (DMARDs) within 3 months of diagnosis. Methotrexate remains the most
commonly prescribed DMARD and is the standard by which recent new and emerging
therapies are measured. Increasing knowledge regarding the immunologic basis of
RA and advances in biotechnology have resulted in new, targeted biological
therapies against proinflammatory cytokines that have dramatically changed the
treatment paradigm and outcomes of patients with RA. This article reviews the
pharmacological rationale underlying RA therapy, with a focus on currently
available biological therapies and new therapies in development.
-----
Geriatrics. 2005 Jun;60(6):28-35.
Rheumatologic illnesses: treatment strategies for older adults.
Blumstein H, Gorevic PD.
Mount Sinai Medical Center, New York, NY, USA.
Basic objectives of arthritis therapy are to reduce musculoskeletal pain, slow
progression of disease, maintain and improve function and quality of life, and
avoid adverse drug reactions. Both nonpharmacologic and pharmacologic approaches
may be taken. The former include patient education, cognitive therapy,
high-intensity progressive-resistance or strength training, weight control, cold
therapy, heat, massage, relaxation and distraction techniques. Guiding
principles for the pharmacologic management of musculoskeletal disease in
geriatric patients are to 'start low and go slow,' and to provide adequate pain
relief. The latter may include the use of topicals, such as 5% lidocaine patches
or capsaicin, or orally administered analgesics, such as acetaminophen, tramadol,
nonsteroidal anti-inflammatory drugs (NSAIDs), and opiates. Although attractive
because of the reduced incidence of serious gastrointestinal adverse reactions,
selective COX-2 inhibitors may have significant renal and cardiovascular
toxicities, and thus should be used with caution in the older patient with
co-morbid diseases affecting these organs. Intraarticular therapies with
corticosteroids, or as viscosupplementation, may have a role in the management
of osteoarthritis. For patients with inflammatory arthropathies, low-dose
systemic steroids or disease-modifying agents are therapeutic. When therapy
fails and pain remains intolerable or disabling, surgical options may be
considered.
-----
Instr Course Lect. 2005;54:251-9.
Surgical treatment of the middle-aged patient with arthritic
knees.
Pagnano MW, Clarke HD, Jacofsky DJ, Amendola A, Repicci JA.
Mayo Clinic, Rochester, Minnesota, USA.
Arthritic knee disease is increasingly more common in the active aging
population. The pathology seen in this patient group can run a spectrum of
localized degenerative change through tricompartmental arthritis. Nonsurgical
options to treat early symptoms are well known and often are effective. When
nonsurgical management has failed, surgical intervention often is warranted.
Arthroscopic debridement is considered in select patients with mechanical
symptoms. Osteotomy continues to have a role in the treatment of young, active
patients and may be particularly appropriate in combination with articular
cartilage procedures. Unicompartmental and total knee arthroplasty are reliable
treatments for patients with advanced stages of degenerative arthritis.
-----
Clin Rheumatol. 2005 Jun 10; [Epub ahead of print]
Intra-articular methotrexate in the treatment of rheumatoid
arthritis and psoriatic arthritis: a clinical and sonographic study.
Iagnocco A, Cerioni A, Coari G, Ossandon A, Masciangelo R, Valesini G.
Department of Clinical and Applied Medical Therapy, Rheumatology Unit,
University of Rome "La Sapienza", Viale del Policlinico 155, Rome, 00161, Italy,
annamaria.iagnocco@uniroma1.it.
The aim of our study was to evaluate the effects of intra-articular methotrexate
(MTX) in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA).
Twenty-three consecutive patients, 10 with RA and 13 with PsA, with prevalent or
unique arthritic involvement of one knee, were treated with intra-articular
injections of MTX 10 mg every 7 days for 8 weeks. Before the beginning of the
treatment and after 9 and 17 weeks, the patients underwent a clinical evaluation
measuring maximal knee flexion angle, visual analog scale (VAS) and erythrocyte
sedimentation rate (ESR). On the same days, an ultrasonographic examination of
the involved knee was performed by two independent experienced operators.
Synovial thickness in the suprapatellar bursa and the presence of joint effusion
and Baker's cyst were assessed. An increase of the mean value of maximal knee
flexion angle and a reduction of the mean values of ESR and VAS between T0, T9
and T17 were demonstrated. Ultrasonographic evaluation showed significant
reduction of synovial thickness and joint effusion. No differences were detected
for the presence of Baker's cyst. We may conclude that repeated intra-articular
injections of MTX resulted in a decrease of local as well as systemic
inflammatory signs. As far as we know, this is the first study that explores the
effects of intra-articular MTX in RA and PsA both clinically and by
ultrasonography.
-----
Semin Arthritis Rheum. 2005 Jun;34(6):819-36.
The Benefit/Risk Profile of TNF-Blocking Agents: Findings of a
Consensus Panel.
Hochberg MC, Lebwohl MG, Plevy SE, Hobbs KF, Yocum DE.
Objective To review the benefits and risks
associated with the use of the tumor necrosis factor (TNF)-blockers in various
indications (eg, rheumatoid arthritis [RA], Crohns disease [CD], psoriasis).
Methods The members of the consensus panel were selected based on their
expertise. Centocor, Inc provided an educational grant to the Center for Health
Care Education to facilitate the consensus panel. Peer-reviewed articles
discussing clinical studies and clinical experiences with TNF-blockers form the
basis of this review. Emerging data that have not been peer-reviewed are also
included. Results The TNF-blockers infliximab, etanercept, and adalimumab are
all approved for treatment of RA. All 3 are effective, and there are currently
no published data from head-to-head clinical trials to support using 1 agent
over another. Preliminary data from small, retrospective studies indicate that
switching among agents to overcome inadequate efficacy or poor tolerability is
beneficial in some patients. The only TNF-blocker currently approved for the
induction and maintenance of remission in CD is infliximab. Preliminary data
indicate that etanercept and infliximab are effective in treating psoriasis.
Some risks associated with TNF-blockers have become apparent, including
congestive heart failure, demyelinating diseases, and systemic lupus
erythematosus, but in most cases can be identified and managed. Several of these
risks (eg, lymphoma and serious infections) are associated with either the
condition per se or the concomitant medication use. Simple screening procedures
help manage the risk of tuberculosis infection; however, it is recommended that
physicians and patients be alert to the development of any new infection so that
appropriate treatment may be initiated promptly. Rare infusion reactions,
particularly with infliximab, may also be effectively managed. Conclusion TNF-blockers
are effective and may be safely used for short- and long-term management of RA
or CD. TNF-blockers also show efficacy in other emerging indications.
-----
Semin Arthritis Rheum. 2005 Jun;34(6):773-84.
Herbal medications commonly used in the practice of rheumatology:
mechanisms of action, efficacy, and side effects.
Setty AR, Sigal LH.
Objective To review the literature on herbal preparations commonly utilized in
the treatment of rheumatic indications. Methods Search of MEDLINE (PubMed) was
performed using both the scientific and the common names of herbs. Relevant
articles in English were collected from PubMed and reviewed. Results This review
summarizes the efficacy and toxicities of herbal remedies used in complementary
and alternative medical (CAM) therapies for rheumatologic conditions, by
elucidating the immune pathways through which these preparations have
antiinflammatory and/or immunomodulatory activity and providing a scientific
basis for their efficacy. Gammalinolenic acid suppresses inflammation by acting
as a competitive inhibitor of prostaglandin E2 and leukotrienes (LTs) and by
reducing the auto-induction of interleukin1alpha (IL-1alpha)-induced
pro-IL-1beta gene expression. It appears to be efficacious in rheumatoid
arthritis (RA) but not for Sjogrens disease. The antiinflammatory actions of
Harpagophytum procumbens is due to its action on eicosanoid biosynthesis and it
may have a role in treating low back pain. While in vitro experiments with
Tanacetum parthenium found inhibition of the expression of intercellular
adhesion molecule-1, tumor necrosis factor alpha (TNF-alpha), interferon-gamma,
IkappaB kinase, and a decrease in T-cell adhesion, to date human studies have
not proven it useful in the treatment of RA. Current experience with
Tripterygium wilfordii Hook F, Uncaria tomentosa , finds them to be efficacious
in the treatment of RA, while Urtica diocia and willow bark extract are
effective for osteoarthritis. T. wilfordii Hook F extract inhibits the
production of cytokines and other mediators from mononuclear phagocytes by
blocking the up-regulation of a number of proinflammatory genes, including TNF-alpha,
cyclooxygenase 2 (COX-2), interferon-gamma, IL-2, prostaglandin, and iNOS.
Uncaria tomentosa and Urtica diocia both decrease the production of TNF-alpha.
At present there are no human studies on Ocimum spp. in rheumatic diseases. The
fixed oil appears to have antihistaminic, antiserotonin, and antiprostaglandin
activity. Zingiber officinale inhibits TNF-alpha, prostaglandin, and leukotriene
synthesis and at present has limited efficacy in the treatment of
osteoarthritis. Conclusions Investigation of the mechanism and potential uses of
CAM therapies is still in its infancy and many studies done to date are
scientifically flawed. Further systematic and scientific inquiry into this topic
is necessary to validate or refute the clinical claims made for CAM therapies.
An understanding of the mechanism of action of CAM therapies allows physicians
to counsel effectively on their proper and improper use, prevent adverse
drug-drug interactions, and anticipate or appreciate toxicities. Relevance The
use of CAM therapies is widespread among patients, including those with
rheumatic diseases. Herbal medications are often utilized with little to no
physician guidance or knowledge. An appreciation of this information will help
physicians to counsel patients concerning the utility and toxicities of CAM
therapies. An understanding and elucidation of the mechanisms by which CAM
therapies may be efficacious can be instrumental in discovering new molecular
targets in the treatment of diseases.
-----
Clin Rheumatol. 2005 Jun;24(3):258-65. Epub 2004 Nov 26.
Effects of shoulder arthroplasty and exercise in patients with
rheumatoid arthritis.
Mengshoel AM, Slungaard B.
Institute of Nursing and Health Sciences, Medical Faculty, University of Oslo,
Box 1153, Blindern, 0316, Oslo, Norway, a.m.mengshoel@medisin.uio.no.
The aim of this study was to examine pain and shoulder function in patients with
rheumatoid arthritis (RA) before and after shoulder arthroplasty and
postoperative exercise. Twenty-four patients (26 shoulders) were consecutively
included in a multicentre study. Before surgery, at discharge from hospital and
after 3 and 6 months, perceived shoulder function and shoulder pain were
assessed by visual analogue scales, activities of daily living by the Modified
Health Assessment Questionnaire (M-HAQ) and shoulder range of motion (ROM) by a
goniometer. All patients showed considerable pain reduction at discharge from
hospital (p<0.001). In those with intact rotator cuff and biceps tendon (n=13)
improvements were found after 6 months in active and passive abduction and
flexion ROMs (p<0.01) and in M-HAQ (p<0.001). Such improvements were not found
in those with torn soft tissue (n=12). Preoperatively, abduction and flexion
motor deficits (passive ROM >active ROM) were found for the total group
(p=0.001). Less flexion motor deficit was found in the intact soft tissue than
in the torn soft tissue group after 3 (p=0.002) and 6 months (p<0.001). No group
difference was found with respect to abduction motor deficit. In conclusion,
pain relief was obtained by all patients. Improvements in ROMs and activities of
daily living were influenced by the state of the soft tissue.
-----
Best Pract Res Clin Rheumatol. 2005 Jun;19(3):345-69.
Joint aspiration and injection.
Courtney P, Doherty M.
Department of Rheumatology Clinical Sciences Building, Nottingham City Hospital,
Nottingham, NG5 1PB, UK.
Joint aspiration/injection is an invaluable procedure for the diagnosis and
treatment of joint disease. The knee is the commonest site to require aspiration
although any non-axial joint is accessible for obtaining synovial fluid. Septic
arthritis and crystal arthritis can be readily diagnosed by aspirating synovial
fluid. Intra-articular injection of long-acting insoluble corticosteroids
produces rapid resolution of inflammation in most injected joints and is a well
established procedure in rheumatological practice. The technique involves only a
knowledge of basic anatomy and should not be unduly painful for the patient.
Provided sterile equipment and a sensible, aseptic approach are used it is a
safe procedure. This chapter addresses the indications, technical principals,
expected benefits and risks of intra-articular corticosteroid injection. The use
of other intra-articular injections including osmic acid, radioisotopes and
hyaluronic acid, which are less universally utilised than intra-articular
corticosteroid, will also be addressed.
-----
Expert Opin Pharmacother. 2005 May;6(5):787-801.
Leflunomide: long-term clinical experience and new uses.
Kaltwasser JP, Behrens F.
Abteilung Rheumatologie, Medizinische Klinik III, Zentrum der Inneren Medizin,
J. W. Goethe-Universitat, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
kaltwasser@em.uni-frankfurt.de
Leflunomide (Arava, Aventis Pharmaceuticals) is an oral pyrimidine synthesis
inhibitor with immunomodulatory and anti-inflammatory activity. This agent has
demonstrated significant efficacy in the treatment of rheumatoid arthritis (RA)
and psoriatic arthritis in randomised, double-blind, placebo-controlled trials.
Both the efficacy and safety of leflunomide are maintained with long-term
administration in patients with RA. Leflunomide compares favourably with other
biological and non-biological agents used to treat RA in the incidence of
adverse events and serious adverse events. Economic studies indicate that
leflunomide is a cost-effective option in the treatment of RA. New
investigations with leflunomide have focused mainly on combination regimens for
the treatment of RA and the use of leflunomide in other inflammatory or
autoimmune disorders.
-----
Aust J Physiother. 2005;51(2):71-85.
Effectiveness of exercise therapy: A best-evidence summary of
systematic reviews.
Smidt N, de Vet HC, Bouter LM, Dekker J.
Institute for Research in Extramural Medicine, VU University Medical Center,
Amsterdam, 1081 BT, The Netherlands. n.smidt@vumc.nl.
The purpose of this project was to summarise the available evidence on the
effectiveness of exercise therapy for patients with disorders of the
musculoskeletal, nervous, respiratory, and cardiovascular systems. Systematic
reviews were identified by means of a comprehensive search strategy in 11
bibliographic databases (08/2002), in combination with reference tracking.
Reviews that included (i) at least one randomised controlled trial investigating
the effectiveness of exercise therapy, (ii) clinically relevant outcome
measures, and (iii) full text written in English, German or Dutch, were selected
by two reviewers. Thirteen independent and blinded reviewers participated in the
selection, quality assessment and data-extraction of the systematic reviews.
Conclusions about the effectiveness of exercise therapy were based on the
results presented in reasonable or good quality systematic reviews (quality
score >/= 60 out of 100 points). A total of 104 systematic reviews were
selected, 45 of which were of reasonable or good quality. Exercise therapy is
effective for patients with knee osteoarthritis, sub-acute (6 to 12 weeks) and
chronic (>/= 12 weeks) low back pain, cystic fibrosis, chronic obstructive
pulmonary disease, and intermittent claudication. Furthermore, there are
indications that exercise therapy is effective for patients with ankylosing
spondylitis, hip osteoarthritis, Parkinson's disease, and for patients who have
suffered a stroke. There is insufficient evidence to support or refute the
effectiveness of exercise therapy for patients with neck pain, shoulder pain,
repetitive strain injury, rheumatoid arthritis, asthma, and bronchiectasis.
Exercise therapy is not effective for patients with acute low back pain. It is
concluded that exercise therapy is effective for a wide range of chronic
disorders.
-----
J Hand Surg [Br]. 2005 May;30(2):217-9.
Total wrist fusion: a study of 115 patients.
Rauhaniemi J, Tiusanen H, Sipola E.
>From the Paimio Hospital, University of Turku, Finland Paimio Hospital, Alvar
Aallon tie, Preitila, Finland.
This retrospective study evaluated the outcome of total wrist fusion,
predominantly using the Mannerfelt technique, in patients with rheumatoid
arthritis. One hundred and fifteen patients were operated on for painful wrist
destruction. The mean pain scores were 3.6 (1-4) pre-operatively, 1.9 (1-4)
after 6 weeks and 1.3 (1-4) at 1 year. Although the radiological fusion rate was
good, only 40% of the patients were very satisfied with the result. Ability to
perform activities of daily living was only very much improved in 30% of the
patients. Grip strength significantly improved after surgery.
-----
Chin J Traumatol. 2005 Apr;8(2):126-8.
Short-term survival analysis of the all-polyethylene tibial
component in total knee arthroplasty.
Shen B, Yang J, Pei FX.
Department of Orthopaedic Surgery, West China Hospital of Sichuan University,
Chengdu 610041, China.
OBJECTIVE: To report the clinical and radiological results of 24 total knee
arthroplasty in which all-polyethylene tibial components were used. METHODS:
Between December 2000 and December 2002, 24 cemented total knee arthroplasty in
21 patients were performed using all-polyethylene tibial components. The mean
age of the 21 patients (9 men and 12 women) at operation was 55 years, ranging
48-61 years. The mean preoperative hospital for special surgery (HSS)score was
40.2 (range, 36-43). The diagnoses were degenerative osteoarthritis in 15
patients, rheumatoid arthritis in 5 and traumatic arthritis in 1. All the
operations were performed by the same surgeon group and there were unilateral
operations in 18 patients and bilateral operations in 3. RESULTS: Eighteen
patients were followed up with a follow-up rate of 85.7%. The mean follow-up is
2.5 years (range, 1-3 years) and mean postoperative HSS scores was 87.5 (range,
83-89). Among them, 18 were excellent, 3 good, 3 poor and none was fair (the
results of three lost patients were classified as poor). Of those reviewed, the
prosthesis was all in situ and no revision occurred. Radiological assessment of
these patients revealed 4 (16.67%) tibial components with radiolucent lines
(mean width<=2 mm) distributed mainly in zone 1 and zone 4. None of these knees
was symptomatic. CONCLUSIONS: The result of total knee arthroplasty using
all-polyethylene tibial components is encouraging. The operative techniques are
similar to those in arthroplasty using metal-backed tibial component.
-----
J Rheumatol Suppl. 2005 Mar;74:3-7.
Differentiating the efficacy of tumor necrosis factor inhibitors.
Haraoui B.
>From the Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec,
Canada.
Blockade of tumor necrosis factor (TNF) has emerged as one of the most promising
therapies in rheumatoid arthritis (RA). Three agents are currently available as
specific TNF antagonists, etanercept (Enbrel(R)), infliximab (Remicade(R)), and
adalimumab (Humira(R)). Data from noncomparative trials suggest that all 3
agents have comparable therapeutic activity in RA. Etanercept and infliximab
have also demonstrated beneficial activity in other inflammatory arthritides
[i.e., psoriatic arthritis and ankylosing spondylitis (both agents) and juvenile
rheumatoid arthritis (etanercept only)] and inflammatory diseases (i.e.,
psoriasis and uveitis). Their effects in granulomatous diseases are more
variable, with only infliximab demonstrating clear efficacy in the treatment of
Crohn's disease, sarcoidosis, and Wegener's vasculitis. In this brief review
current efficacy data are summarized and possible explanations for observed
clinical differences are explored.
-----
J Rheumatol. 2005 Mar;32(3):417-23.
A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial
of LY333013, a Selective Inhibitor of Group II Secretory Phospholipase A2, in
the Treatment of Rheumatoid Arthritis.
Bradley JD, Dmitrienko AA, Kivitz AJ, Gluck OS, Weaver AL, Wiesenhutter C, Myers
SL, Sides GD.
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
OBJECTIVE: To evaluate the efficacy and safety of a selective inhibitor of
secretory phospholipase (sPLA2), LY333013, in the treatment of rheumatoid
arthritis (RA). METHODS: Two hundred and fifty-one patients with active RA
despite treatment with one or more disease modifying antirheumatic drugs (DMARD)
received oral doses of LY333013 (50, 250, and 1000 mg) or placebo once daily for
12 weeks. Concomitant low-dose glucocorticoids (</= 10 mg/day prednisone
equivalent) were allowed. Clinical improvement was assessed using the response
criteria of the American College of Rheumatology (ACR20), and safety was
evaluated with respect to adverse events and laboratory test abnormalities.
RESULTS: The demographic characteristics of the treatment groups were similar.
Dose-response relationships were found for ACR20 responses (p = 0.058) and
reductions in C-reactive protein (p = 0.058) at week 1. The proportions of
patients with an ACR20 response subsequently increased in all study groups
including the placebo group at weeks 4 and 8, and the initial treatment benefit
was lost. Adverse events were generally mild in severity and not associated with
treatment. CONCLUSION: Treatment with LY333013 for 12 weeks was well tolerated
but ineffective as an adjunct to DMARD treatment of active RA.
-----
Handchir Mikrochir Plast Chir. 2005 Feb;37(1):52-9.
[Aims of hand therapy in treatment of rheumatoid hand]
[Article in German]
Bureck W.
Nordwestdeutsches Rheumazentrum, Orthopadisches Zentrum, Abteilung Ergotherapie,
St. Josef-Stift Sendenhorst, Sendenhorst. bureck@st-josef-stift.de
When dealing with rheumatoid arthritis, the main issues of hand therapy are the
treatment of hand and finger joints. We emphasize mobilisation of joints, muscle
strengthening, correcting deformities by low temperature splints and joint
protection. Further tasks of occupational therapy are: Informing patients about
adaptive devices and training their use as well as educational programs for
patients with reduced mobility of the upper limb. The most common surgery on the
rheumatoid hand, that need postoperative treatment by a hand therapist are
complete and limited arthrodesis of the wrist, surgical reconstruction of
tendons, arthroplasty and arthrodeses of and for finger joints, and so on. At
the Nordwestdeutsches Rheumazentrum St. Josef-Stift Sendenhorst we have designed
a standard postoperative management for treating arthroplasty with a "Silikonspacer"
in the metacarpophalangeal joints.
-----
Handchir Mikrochir Plast Chir. 2005 Feb;37(1):13-7.
[Early results of NeuFlex silastic implant in MCP arthroplasty]
[Article in German]
Schindele S, Herren D, Flury M, Simmen BR.
Abteilung fur Obere Extremitat und Handchirurgie, Schulthess-Klinik, Zurich,
Schweiz. stephan.schindele@kssg.ch
For the reconstruction of destroyed metacarpophalangeal (MP) joints in
rheumatoid arthritis, the Swanson silicon spacer is still the golden standard.
However, long-term follow-up reveals an increasing number of complications,
particularly mechanical failure. In order to deal with these problems a number
of new, biomechanically different silicone implants have been designed. Among
these, the NeuFlex prosthesis has a preflexed hinge of 30 degrees in relation to
the shaft axis, a more palmar lying center of rotation and a rectangular hinge
with a collarlike platform against the bony surfaces. In a prospective study,
the early results of the first thirteen patients operated with the NeuFlex
arthroplasty are reported. All patients suffered from rheumatoid arthritis with
destruction of the MP joints. The mean follow-up was 12.3 months. A total of 37
joints were replaced. All patients were female with an average age of 56 years.
Postoperative reduction of pain, measured on a visual analog scale with the
maximum of 10 (VAS), decreased from 6.6 to 0.7 (p < 0.001). Jamar grip strength
improved from 4.2 kg preoperatively to 9.9 kg postoperatively (p < 0.005). Range
of motion improved from 37 degrees to 57 degrees (p < 0.0001) as a result of a
reduction in active extension deficit which reduced from 35 degrees to 15
degrees postoperatively. Ulnar drift was reduced from 20.2 degrees to 3.4
degrees at follow-up (p < 0.005). Radiological evaluation showed no implant
failure, no subsidence, and no signs of inflammatory reaction. Overall the
NeuFlex silicone implants show encouraging early results which must be confirmed
in the long term.
-----
Handchir Mikrochir Plast Chir. 2005 Feb;37(1):7-12.
[The WEKO finger joint prosthesis]
[Article in German]
Wessels KD.
Orthopadische Abteilung, Marienhospital Gelsenkirchen. egoerz@st-augustinus.de
The WEKO prosthesis was developed between 1989 and 1993 in order to restore
stability and function of destroyed metacarpophalangeal joints in rheumatoid
arthritis. The prosthesis is a hinged one and is fixed to the bone cementlessly
by special osseointegrated sleeves in which the stem of the implant is fastened
by a cone. Forty-eight patients with 74 prosthesis have been operated on in
1993. In a follow-up study in 2003, 43 of them (89.5 %) with 65 prostheses (87.8
%) could be re-examined clinically and radiographically. In seven patients (16.2
%) implant arthroplasty failed comprising loosening of the prosthesis within
their sleeves, loosening of the sleeves in the bone and implant breakage. Twelve
implants (16.2 %) had to be removed. The range of motion at follow-up was
0/10/70 degrees in comparison to 0/0/90 degrees postoperatively. Patients
satisfaction over the first three to four years was higher than later due to
deterioration of the rheumatoid disease. Thus, classical handscores to assess
the outcome could not be applied. A second generation of the WEKO prosthesis was
developed to improve rotational stability and osseointegration paying attention
to reports concerning failures which were seen also by other authors. The stem
of the implant was changed to a cylindrical one with star shaped cross-section
which allows some pistoning in order to reduce the stressload of the sleeves.
-----
Clin Ther. 2005 Jan;27(1):64-77.
Efficacy and tolerability of lumiracoxib in the treatmentof
osteoarthritis of the knee: A 13-week, randomized, double-blind comparison with
celecoxib and placebo.
Sheldon E, Beaulieu A, Paster Z, Dutta D, Yu S, Sloan VS.
Miami Research Associates, Miami, Florida, USA.
BACKGROUND:: Lumiracoxib is a cyclooxygenase-2-selectiveinhibitor developed for
the treatment of osteoarthritis (OA), rheumatoid arthritis, and acute pain.
OBJECTIVES:: This study assessed the efficacy and tolerability of lumiracoxib
100 mg QD compared with celecoxib and placebo in patients with OA of the knee.
METHODS:: In this 13-week, double-blind, double-dummy,placebo-controlled,
parallel-group study, patients with primary OA of the knee and pain intensity in
the target knee a40 mm on a 100-mm visual analog scale after a 3- to 7-day
washout of nonsteroidal anti-inflammatory drugs were randomized to receive
lumiracoxib 100 mg QD, lumiracoxib 100 mg QD with a loading dose of lumiracoxib
200 mg QD for the first 2 weeks, celecoxib 200 mg QD, or placebo. Three primary
efficacy variables were assessed at the end of the study: pain intensity in the
target knee, the patient's global assessment of disease activity, and functional
status (Western Ontario and McMaster Universities Osteoarthritis Index total
score). In addition, the treatment response was assessed using the Outcome
Measures in Clinical Trials-Osteoarthritis Research Society International (OMERACT
OARSI) criteria. The safety profile and tolerability of all treatments were also
examined. RESULTS:: The study enrolled 1551 patients (primarily white; 62%
female; mean age, 60.5 years): 391 were randomized to receive lumiracoxib 100 mg
QD, 385 lumiracoxib 100 mg QD with a loading dose, 393 celecoxib 200 mg QD, and
382 placebo. Treatment groups were closely balanced at baseline with respect to
demographic and disease characteristics. Lumiracoxib was superior to placebo (P
< 0.001) and similar to celecoxib on all primary efficacy variables. Reductions
in pain intensity in the target knee were similar in the 2 lumiracoxib groups at
week 13 (estimated least square mean difference vs placebo: -6.7 and -8.1 mm for
lumiracoxib 100 mg QD and lumiracoxib 100 mg QD with loading dose, respectively;
both, P < 0.001); with celecoxib, the estimated least square mean difference was
-5.7 mm (P < 0.001). Significant differences compared with placebo were seen in
all variables starting at week 2 for all active treatments (all, P < 0.001). No
significant differences were seen between the lumiracoxib groups at any time
point. Based on OMERACT OARSI criteria, all active treatments were superior to
placebo (all, P < 0.001). Lumiracoxib and celecoxib were well tolerated, with an
incidence of adverse events similar to that with placebo (64.7% lumiracoxib 100
mg QD, 67.0% lumiracoxib 100 mg QD with loading dose, 58.8% celecoxib, 58.4%
placebo). CONCLUSION:: In this population of patients with OA of the knee,
lumiracoxib 100 mg QD was of similar efficacy to celecoxib 200 mg QD and had
similar tolerability to placebo.
-----
Drugs. 2005;65(5):661-94.
Efficacy, tolerability and cost effectiveness of
disease-modifying antirheumatic drugs and biologic agents in rheumatoid
arthritis.
Nurmohamed MT, Dijkmans BA.
Departments of Rheumatology, VU University Medical Centre, Amsterdam, The
NetherlandsJan van Breemen Institute, Amsterdam, The Netherlands.
Over the last decade, several new drugs have become available for the treatment
of patients with rheumatoid arthritis. These agents include the new
disease-modifying antirheumatic drug (DMARD) leflunomide and the biologic
agents, tumor necrosis factor (TNF)-alpha antagonists and an interleukin (IL)-1
receptor antagonist.Methotrexate is commonly used as the first DMARD, has a well
documented clinical efficacy and slows radiological deterioration. Sulfasalazine
appears to have similar properties, albeit to a lesser extent. Leflunomide has
similar efficacy as methotrexate but it is less tolerated than sulfasalazine.
The adverse effect profiles of these three drugs makes regular laboratory
monitoring mandatory.Several combination therapies with DMARDs were proven to be
more effective than mono-DMARD therapy. However, until now these strategies have
not been widely adopted.TNF antagonists are potent anti-inflammatory drugs, with
a rapid onset of effects compared with traditional DMARDs. The IL-1 receptor
antagonist, anakinra, has an intermediate place between methotrexate and the TNF
antagonists with respect to efficacy.The adverse effects of TNF antagonists
include an increased incidence of common and opportunistic infections. Thus far,
anakinra has not been associated with an enhanced rate of opportunistic
infections.Some of the biologic agents have been associated with worsening heart
failure and demyelinating disease. The limited long-term safety data of the
biologic agents are a point of concern because, at present, an enhanced risk for
malignancies, particularly lymphoma, can not be excluded.Drug costs of
traditional DMARDs are up to $US3000 per year, whereas for the biologics the
yearly drug costs range between $US16 000 and >$US20 000. Cost-effectiveness
analyses are necessary to determine whether or not these high costs are
justified. Unfortunately, adequate, prospective, economic evaluations are not
yet available. Until these become available, treatment decisions will be based
on the balance of direct costs and indirect costs and expected cost savings in
the future.
-----
J Dermatolog Treat. 2004 Dec;15(6):348-52.
Adalimumab (Humira): a brief review for dermatologists.
Scheinfeld N.
St Luke's Roosevelt Hospital Center, New York, NY 10025, USA. NSS32@columbia.edu
Adalimumab is a new purely human TNF-alpha monoclonal antibody that has been
approved for the treatment of rheumatoid arthritis as monotherapy or in
combination with methotrexate. It is administered by subcutaneous injection in a
40-mg dose every other week. The one published Phase II trial of adalimumab for
psoriasis has provided very encouraging results for its efficacy. Its most
important side effects relate to the development of infection while it is being
used. It is a promising medication and research regarding its use continues.
-----
Curr Dir Autoimmun. 2005;8:175-92.
B lymphocyte depletion in rheumatoid arthritis: targeting of
CD20.
Edwards JC, Leandro MJ, Cambridge G.
Centre for Rheumatology, University College London, London, UK. jo.edwards@ucl.ac.uk
BACKGROUND: During the 1990s evidence emerged to suggest that B lymphocyte
depletion in rheumatoid arthritis (RA) might be of major benefit. METHODS AND
RESULTS: In 1997 the B lympholytic monoclonal anti-CD20 antibody rituximab
became available. Significant clinical efficacy has been demonstrated in RA,
initially in open studies at University College London and recently in a
multicentre randomised controlled trial. Forty RA patients at University College
London have now received in total 75 treatment cycles with rituximab (up to 4
individually) alone or in combination with corticosteroid, cyclophosphamide
and/or methotrexate. Ongoing immunodynamic studies of these patients have shed
light on a number of questions about both the therapeutic potential of B cell
targeting, and the pathogenesis of RA. CONCLUSIONS: The effects of B lymphocyte
depletion lend increasing support to the idea that both the inflammatory
effector mechanism and the underlying immunoregulatory disturbance in RA are
driven by autoantibody rather than T cells.
-----
Ann Rheum Dis. 2004 Dec 2; [Epub ahead of print]
Tolerance and short-term efficacy of rituximab in 43 patients
with systemic autoimmune diseases.
Gottenberg J, Guillevin L, Lambotte O, Combe B, Allanore Y, Cantagrel A,
Larroche C, Soubrier M, Bouillet L, Dougados M, Fain O, Farge D, Kyndt X,
Lortholary O, Masson C, Moura B, Remy P, Thomas T, Wendling D, Anaya J, Sibilia
J, For The Club Rhumatismes Et Inflammation Cri XM.
Hopital de Bicetre, (AP-HP), Le Kremlin-Bicetre.
OBJECTIVE: To assess the tolerance and efficacy of rituximab in patients with
various autoimmune diseases seen in daily rheumatological practice. Patients and
METHODS: Eight hundred and sixty-six rheumatology and internal medicine
practitioners were contacted by E-mail to obtain the files of patients treated
with rituximab for systemic autoimmune diseases. Patients with lymphoma were
analysed if the evolution of the autoimmune disease could be evaluated. RESULTS:
A total of 43 of 49 cases could be analysed in this retrospective
study,including 14 patients with rheumatoid arthritis (RA), 13 with systemic
lupus erythematosus (SLE), 6 with primary Sjogren's syndrome (pSS), 5 with
systemic vasculitis and 5 with other autoimmune diseases. Rituximab was
prescribed for lymphoma in 2 patients with RA and 2 with pSS. In the 39 other
cases, rituximab was given because of the refractory character of the autoimmune
disease. The mean follow-up period was 8.3 months (2-26 months). Eleven adverse
events were observed in 10 patients and treatment had to be discontinued in 6
patients. The efficacy of rituximab was observed in 30 patients (70%): 11 RA, 9
SLE, 5 pSS, 2 vasculitis, 2 antisynthetase syndromes and 1 sarcoidosis. The mean
decrease in daily corticosteroid intake was 9.5 mg/day (0-50) in responders.
Seven patients experienced relapse after 8.1 months (5-15), on average. Three
patients died because of refractory autoimmune disease. CONCLUSION: Despite the
absence of marketing authorization, rituximab is used to treat various
refractory autoimmune diseases in daily rheumatological practice. The present
study shows good tolerance, short-term clinical efficacy and marked
corticosteroid reduction with rituximab therapy in patients with RA, SLE, pSS,
vasculitis or polymyositis.
-----
Ann Rheum Dis. 2004 Dec;63(12):1571-5.
Atorvastatin reduces arterial stiffness in patients with
rheumatoid arthritis.
Van Doornum S, McColl G, Wicks IP.
Department of Rheumatology, The Royal Melbourne Hospital, Parkville VIC 3050
Australia. sharon.vandoornum@mh.org.au.
BACKGROUND: Chronic systemic inflammation may contribute to accelerated
atherosclerosis and increased arterial stiffness in patients with rheumatoid
arthritis (RA). In addition to lowering cholesterol, statins have
immunomodulatory effects which may be especially beneficial in patients with RA
who have systemic immune activation. OBJECTIVE: To investigate the effect of
atorvastatin on the augmentation index (AIx: a measure of arterial stiffness)
and systemic inflammation in RA. METHODS: 29 patients with RA (mean (SD) age 55
(13) years) with moderately active disease of long duration were studied. AIx,
lipid levels, serum inflammatory markers, and disease activity score were
measured before and after 12 weeks of atorvastatin 20 mg daily. RESULTS: AIx
improved significantly from 34.1 (11.6)% to 29.9 (11)% (p = 0.0002), with the
greatest improvements in AIx occurring in those subjects with the highest
disease activity scores (r = -0.5, p = 0.007). Total and LDL cholesterol were
reduced from 5.5 (0.9) to 3.9 (0.7) mmol/l and 3.3 (0.8) to 1.9 (0.6) mmol/l,
respectively (p = 0.0001). Serum inflammatory markers remained unchanged during
the study. CONCLUSIONS: Atorvastatin significantly reduced arterial stiffness in
patients with RA. The greatest improvements were seen in patients with more
active disease, suggesting that, in addition to the beneficial effects of
cholesterol reduction, immune modulation may contribute to the cardioprotective
effect of statins.
-----
Clin Orthop. 2004 Dec;1(429):316-329.
Orthopaedic Gene Therapy.
Evans CH, Ghivizzani SC, Robbins PD.
>From the *Center for Molecular Orthopaedics, Harvard Medical School, Boston,
MA; the daggerDepartment of Orthopaedics and Rehabilitation, University of
Florida; and the double daggerDepartment of Molecular Genetics and Biochemistry,
University of Pittsburgh School of Medicine, Pittsburgh, PA.
We review progress in the field of orthopaedic gene therapy since the concept of
using gene transfer to address orthopaedic problems was initiated approximately
15 years ago. The original target, arthritis, has been the subject of two
successful Phase I clinical trials, and additional human studies are pending in
rheumatoid arthritis and osteoarthritis. The repair of damaged musculoskeletal
tissues also has proved to be a fruitful area of research, and impressive
enhancement of bone healing has been achieved in preclinical models. Rapid
progress also is being made in the use of gene transfer to improve cartilage
repair, ligament healing, and restoration of various additional tissues,
including tendon and meniscus. Other applications include intervertebral disc
degeneration, aseptic loosening, osteoporosis, genetic diseases, and orthopaedic
tumors. Of these various orthopaedic targets of gene therapy, tissue repair is
likely to make the earliest clinical impact because it can be achieved with
existing technology. Tissue repair may become one of the earliest clinical
successes for gene therapy as a whole. Orthopaedics promises to be a leading
discipline for the use of human gene therapy.
-----
J Rheumatol. 2004 Dec;31(12):2507-12.
Comparison of the intraarticular effectiveness of triamcinolone
hexacetonide and triamcinolone acetonide in treatment of juvenile rheumatoid
arthritis.
Eberhard BA, Sison MC, Gottlieb BS, Ilowite NT.
Division of Rheumatology, Schneider Children's Hospital, New Hyde Park, New
York, USA.
OBJECTIVE: To compare patients with juvenile rheumatoid arthritis (JRA) injected
with triamcinolone hexacetonide (TH) or triamcinolone acetonide (TA) with
respect to time to relapse. METHODS: This was a retrospective chart review of 85
patients: 51 patients with JRA who had received a joint injection with TH during
the period June 2000-April 2001 and 48 patients who had received a joint
injection with TA during the period May 2001-March 2002 who were followed for a
minimum of 15 months, after an intraarticular steroid injection. RESULTS: The
primary endpoint variable for the study was the time to relapse of the arthritis
in the affected joint following an intraarticular injection. A total of 227
joints were injected, 114 with TH and 113 with TA. In the TH group the mean time
to relapse (+/- SE) was 10.14 +/- 0.49 months compared to the TA group at 7.75
+/- 0.49 months (p < 0.0001) using the log-rank test. A proportional hazards
(Cox) regression analysis revealed no statistical association between sex,
duration of illness, or type of arthritis and relapse time. An analysis was
performed on the first intraarticular injection for each patient, with the
average time to relapse for all joints injected of 10.36 +/- 0.72 months for TH
compared to 8.45 +/- 0.78 months for TA (p < 0.02). A further analysis of the
first knee injections showed a relapse time in the TH group of 11.11 +/- 0.81
months compared to 7.95 +/- 0.95 months for TA (p < 0.008). CONCLUSION: TH
offers an advantage to TA, as there is a longer duration of action leading to an
improved prolonged response rate in weight-bearing joints, particularly the
knees. The results suggest that TH should be the intraarticular steroid of
choice, particularly for the knee joint, in patients with JRA.
-----
J Rheumatol. 2004 Dec;31(12):2356-9.
Clinical outcomes of patients with rheumatoid arthritis after
switching from infliximab to etanercept.
Haraoui B, Keystone EC, Thorne JC, Pope JE, Chen I, Asare CG, Leff JA.
Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada.
OBJECTIVE: To assess the efficacy and monitor serious adverse events in patients
with rheumatoid arthritis (RA) switching treatment from infliximab to etanercept.
METHODS: Adult patients with active RA who were discontinuing treatment with
infliximab were eligible to enroll in this prospective, 12-week, open label,
single-arm, observational study. Four to 10 weeks after their last infusion of
infliximab, patients began treatment with etanercept (twice weekly subcutaneous
injections of 25 mg). Clinical assessments using the American College of
Rheumatology (ACR) criteria for improvement were performed at baseline and at
Weeks 6 and 12, and serious adverse events were monitored throughout the study.
RESULTS: Twenty-five patients were enrolled, 18 of whom had discontinued
infliximab because of lack of efficacy, and 22 completed 12 weeks of etanercept
treatment. After 12 weeks, 14 of 22 patients (64%) achieved at least a 20%
improvement in ACR criteria (ACR20), 13 (59%) experienced improvements in
physical function that were considered clinically important (>/= 0.22 point
decrease in overall Health Assessment Questionnaire score), and mean values of
all individual components of the ACR criteria had improved. No serious adverse
events were reported during the study and no patient discontinued because of
lack of efficacy. CONCLUSION: Etanercept, a soluble tumor necrosis factor (TNF)
receptor, provided a well tolerated and effective treatment option for some
patients even when infliximab, a monoclonal antibody to TNF, had been
ineffective.
-----
Rev Gastroenterol Disord. 2004 Fall;4(4):196-210.
Adalimumab: human recombinant immunoglobulin g1 anti-tumor
necrosis factor monoclonal antibody.
Baker DE.
College of Pharmacy, Washington State University, Spokane, Washington, USA.
Tumor necrosis factor (TNF) is a proinflammatory cytokine that is involved with
normal inflammatory and immune responses and with the pathogenesis of chronic
inflammatory medical conditions, such as rheumatoid arthritis, psoriatic
arthritis, plaque psoriasis, and Crohn's disease. The newest therapies for these
inflammatory conditions include the TNF biologic response modifiers infliximab,
etanercept, and adalimumab. Adalimumab is a human recombinant immunoglobulin G1
anti-TNF monoclonal antibody. As monotherapy, or in combination with
methotrexate or other traditional disease-modifying antirheumatic drugs,
adalimumab can produce improvements in the signs and symptoms associated with
rheumatoid arthritis and can slow progression of the joint destruction. The
adverse effect profile of adalimumab seems to be comparable to that of
etanercept. Adalimumab also seems to be useful in the treatment of psoriasis,
psoriatic arthritis, and Crohn's disease; however, none of these indications are
approved by the US Food and Drug Administration, and the optimal dosing regimen
for these indications has not been established.
-----
Clin Exp Rheumatol. 2004 Sep-Oct;22(5 Suppl 35):S101-7.
Benefit/risk of cyclosporine in rheumatoid arthritis.
Gremese E, Ferraccioli GF.
Division of Rheumatology, Catholic University of the Sacred Heart, School of
Medicine, CIC-Via Moscati 31, 00168 Rome, Italy.
Combination therapy has emerged as a crucial therapeutic tool to control
aggressive rheumatoid arthritis (RA). Cyclosporine (CsA) when combined with
methotrexate (MTX) has shown substantial benefit in clinical practice. The
primary benefit is its positive effect in the control of joint-bone erosions.
The most feared adverse effect is the development of nephrotoxicity, which may
be in part hemodynamic and in part structural, i.e. fibrotic. Careful monitoring
of concomitant drugs, hypertension and through blood levels should allow the
patient to maintain normal renal function. The successful employment of CsA in
lupus nephritis clearly supports this statement.
-----
Clin Exp Rheumatol. 2004 Sep-Oct;22(5 Suppl 35):S77-82.
Glucocorticoid use in rheumatoid arthritis: benefits, mechanisms,
and risks.
Townsend HB, Saag KG.
Center for Education and Research on Therapeutics of Musculoskeletal Disorders,
Division of Clinical Immunology and Rheumatology, University of Alabama at
Birmingham 35294-3408, USA.
Glucocorticoids have long been recognized to have beneficial effects in
rheumatoid arthritis (RA) (1,2). Several clinical trials over the last decade
have further documented the efficacy of glucocorticoids in relieving
inflammation and in preventing radiographic erosions in early RA (3-5).
Additionally, research has yielded new insights about the cellular mechanisms
responsible for these perceived beneficial effects (6,7). Despite potential
short term benefits, there is a lack of demonstrated long-term efficacy as well
as concerns about short and long-term toxicity. Although these concerns have
limited enthusiasm for glucocorticoids by many patients and practitioners, in
the U.S. it is estimated that 44% to 75% of RA patients use glucocorticoids
(8,9). Confusion and controversy may relate to the fact that toxicity reports
are also limited by only modest data quality and quantity. Given growing
clinical and basic science evidence supporting the efficacy of glucocorticoids
for the treatment of rheumatoid arthritis, their use may further increase. In
this review we will examine the latest data supporting the benefits and risks of
glucocorticoid use in RA.
-----
Pain. 2004 Oct;111(3):286-96.
Efficacy and safety of valdecoxib for treatment of osteoarthritis
and rheumatoid arthritis: systematic review of randomised controlled trials.
Edwards JE, McQuay HJ, Moore RA.
Pain Research and Nuffield Department of Anaesthetics, University of Oxford,
Oxford Radcliffe Hospital, The Churchill, Headington, Oxford OX3 7LJ, UK.
Our objective was to determine the efficacy and safety of valdecoxib (a
cyclo-oxygenase 2 inhibitor) in the treatment of arthritis. Randomised,
controlled trials comparing 10 or 20mg valdecoxib with placebo or non-steroidal
anti-inflammatory drugs (NSAIDs) in patients with active osteoarthritis or
rheumatoid arthritis. The manufacturer provided clinical trial reports. Data
were combined through meta-analysis. Main outcomes were patient global rating of
arthritis, arthritis pain, Western Ontario and McMaster Universities indices for
osteoarthritis, American College of Rheumatology indices for rheumatoid
arthritis, discontinuation, endoscopic ulcers, clinically significant upper
gastrointestinal or renal events. Nine trials (five in osteoarthritis, four in
rheumatoid arthritis) were included with 5726 patients. Overall, valdecoxib 10
and 20mg were superior to placebo and equivalent in efficacy to maximum daily
doses of NSAIDs. Significantly fewer discontinuations because of
gastrointestinal adverse events (4% versus 8%), or endoscopic ulcers of 3mm or
more (5% versus 13%) occurred with valdecoxib compared with NSAIDs. Clinically
significant upper gastrointestinal events occurred in 2/2733 (0.1%) with
valdecoxib compared with 8/1846 (0.4%) with NSAIDs. Rates of clinically
significant renal events were the same (2-3%) for valdecoxib and NSAIDs. At an
appropriate dose valdecoxib was as effective as NSAIDs in osteoarthritis and
rheumatoid arthritis. There were fewer gastrointestinal adverse event
withdrawals and endoscopically detected ulcers. Convincing evidence of reduced
major gastrointestinal adverse events could not be addressed by the trials.
-----
Ann Rheum Dis. 2004 Oct;63(10):1318-26.
Autologous stem cell transplantation for refractory juvenile
idiopathic arthritis: analysis of clinical effects, mortality, and transplant
related morbidity.
De Kleer IM, Brinkman DM, Ferster A, Abinun M, Quartier P, Van Der Net J, Ten
Cate R, Wedderburn LR, Horneff G, Oppermann J, Zintl F, Foster HE, Prieur AM,
Fasth A, Van Rossum MA, Kuis W, Wulffraat NM.
Paediatric BMT unit, Suite KC 03.063, University Medical Centre Utrecht, PO box
85090, 3508 AB Utrecht, Netherlands.
OBJECTIVE: To evaluate the safety and efficacy of autologous stem cell
transplantation (ASCT) for refractory juvenile idiopathic arthritis (JIA).
DESIGN: Retrospective analysis of follow up data on 34 children with JIA who
were treated with ASCT in nine different European transplant centres.
Rheumatological evaluation employed a modified set of core criteria.
Immunological reconstitution and infectious complications were monitored at
three month intervals after transplantation. RESULTS: Clinical follow up ranged
from 12 to 60 months. Eighteen of the 34 patients (53%) with a follow up of 12
to 60 months achieved complete drug-free remission. Seven of these patients had
previously failed treatment with anti-TNF. Six of the 34 patients (18%) showed a
partial response (ranging from 30% to 70% improvement) and seven (21%) were
resistant to ASCT. Infectious complications were common. There were three cases
of transplant related mortality (9%) and two of disease related mortality (6%).
CONCLUSIONS: ASCT in severely ill patients with JIA induces a drug-free
remission of the disease and a profound increase in general wellbeing in a
substantial proportion of patients, but the procedure carries a significant
mortality risk. The following adjustments are proposed for future protocols: (1)
elimination of total body irradiation from the conditioning regimen; (2)
prophylactic administration of antiviral drugs and intravenous immunoglobulins
until there is a normal CD4+ T cell count.
-----
Ann Rheum Dis. 2004 Oct;63(10):1232-4.
Better efficacy of methotrexate given by intramuscular injection
than orally in patients with rheumatoid arthritis.
Wegrzyn J, Adeleine P, Miossec P.
Clinical Immunology Unit, Departments of Immunology and Rheumatology, Hopital
Edouard Herriot, Lyon, 69437 Lyon Cedex 03, France.
OBJECTIVE: To compare the clinical efficacy of methotrexate and tolerance to the
drug in patients with rheumatoid arthritis who were switched from intramuscular
to oral administration because of a shortage of the intramuscular preparation.
METHODS: 143 patients were switched from intramuscular to oral methotrexate. Of
these, 47 were switched back to the intramuscular form. A multiple choice
questionnaire was sent by mail to evaluate clinical and biological criteria of
efficacy and tolerance. RESULTS: When methotrexate was first switched from
intramuscular to oral administration, increased disease activity, exacerbation
of morning pain and hand stiffness, duration of morning stiffness, increased
joint pain, and increased joint swelling were observed. There was a greater
frequency of gastrointestinal symptoms, but without a significant increase in
liver abnormalities. When intramuscular methotrexate became available again, 47
of the 143 patients were switched back and were followed for at least three
months. On average, disease manifestations were improved and side effects
reduced by the switch. CONCLUSIONS: Methotrexate given intramuscularly had
improved clinical efficacy with fewer side effects than given orally.
Intramuscular methotrexate administration should be considered when rheumatoid
arthritis remains active in spite of high dose oral methotrexate.
-----
Drugs. 2004;64(19):2237-46.
Lumiracoxib.
Lyseng-Williamson KA, Curran MP.
Adis International Limited, Auckland, New Zealand.
Lumiracoxib is a highly selective and potent cyclo-oxygenase (COX)-2 inhibitor,
with a novel structure that conveys weakly acidic properties and a unique
pharmacological profile. It is rapidly absorbed, with a relatively short plasma
half-life. In well designed clinical trials of 1-52 weeks' duration in patients
with osteoarthritis (OA) or rheumatoid arthritis, the efficacy of oral
lumiracoxib 100-400 mg/day in decreasing pain intensity and improving functional
status was greater than that with placebo and similar to those with nonselective
NSAIDs or celecoxib 200mg once daily. In single- and multiple-dose well designed
trials in patients with acute pain associated with primary dysmenorrhoea, dental
or orthopaedic surgery or tension-type headache, lumiracoxib 100-800mg once
daily was more effective in relieving acute pain than placebo or
controlled-release oxycodone 20mg, and was at least as effective as selective
COX-2 inhibitors or nonselective NSAIDs. Lumiracoxib was generally well
tolerated in clinical trials, with a similar overall tolerability profile to
those of placebo and other COX-2-selective inhibitors. In a large 52-week safety
trial in patients with OA, lumiracoxib 400mg once daily had a rate of
gastrointestinal ulcer complications that was approximately one-third to
one-quarter of that of ibuprofen 800mg three times daily or naproxen 500mg twice
daily. Lumiracoxib was not associated with an increase in cardiovascular events.
-----
Drugs. 2004;64(20):2315-43.
Nabumetone: therapeutic use and safety profile in the management
of osteoarthritis and rheumatoid arthritis.
Hedner T, Samulesson O, Wahrborg P, Wadenvik H, Ung KA, Ekbom A.
Department of Clinical Pharmacology, Sahlgrenska University Hospital, Goteborg,
Sweden.
Nabumetone is a nonsteroidal anti-inflammatory prodrug, which exerts its
pharmacological effects via the metabolite 6-methoxy-2-naphthylacetic acid
(6-MNA). Nabumetone itself is non-acidic and, following absorption, it undergoes
extensive first-pass metabolism to form the main circulating active metabolite
(6-MNA) which is a much more potent inhibitor of preferentially cyclo-oxygenase
(COX)-2. The three major metabolic pathways of nabumetone are O-demethylation,
reduction of the ketone to an alcohol, and an oxidative cleavage of the
side-chain occurs to yield acetic acid derivatives. Essentially no unchanged
nabumetone and <1% of the major 6-MNA metabolite are excreted unchanged in the
urine from which 80% of the dose can be recovered and another 10% in
faeces.Nabumetone is clinically used mainly for the management of patients with
osteoarthritis (OA) or rheumatoid arthritis (RA) to reduce pain and
inflammation. The clinical efficacy of nabumetone has also been evaluated in
patients with ankylosing spondylitis, soft tissue injuries and juvenile RA.The
optimum oral dosage of nabumetone for OA patients is 1g once daily, which is
well tolerated. The therapeutic response is superior to placebo and similar to
nonselective COX inhibitors. In RA patients, nabumetone 1g at bedtime is
optimal, but an additional 0.5-1g can be administered in the morning for
patients with persistent symptoms. In RA, nabumetone has shown a comparable
clinical efficacy to aspirin (acetylsalicylic acid), diclofenac, piroxicam,
ibuprofen and naproxen.Clinical trials and a decade of worldwide safety data and
long-term postmarketing surveillance studies show that nabumetone is generally
well tolerated. The most frequent adverse effects are those commonly seen with
COX inhibitors, which include diarrhoea, dyspepsia, headache, abdominal pain and
nausea.In common with other COX inhibitors, nabumetone may increase the risk of
GI perforations, ulcerations and bleedings (PUBs). However, several studies show
a low incidence of PUBs, and on a par with the numbers reported from studies
with COX-2 selective inhibitors and considerably lower than for nonselective COX
inhibitors. This has been attributed mainly to the non-acidic chemical
properties of nabumetone but also to its COX-1/COX-2 inhibitor profile. Through
its metabolite 6-MNA, nabumetone has a dose-related effect on platelet
aggregation, but no effect on bleeding time in clinical studies. Furthermore,
several short-term studies have shown little to no effect on renal
function.Compared with COX-2 selective inhibitors, nabumetone exhibits similar
anti-inflammatory and analgesic properties in patients with arthritis and there
is no evidence of excess GI or other forms of complications to date.
-----
Indian J Pediatr. 2004 Sep;71(9):819-24.
Management of septic arthritis.
Shetty AK, Gedalia A.
Department of Pediatrics, Wake Forest University School of Medicine and Brenner
Children's Hospital, Winston-Salem, North Carolina, USA. avishetty@pol.net
Septic arthritis in children remains a serious disease with the potential for
significant systemic and musculoskeletal morbidity. Staphlococcus aureus is the
most common cause of bone and joint infections in all age groups. Microbial
invasion of the synovial space occurs typically results from hematogenous
seeding. Diagnosis in neonates and young infants can be difficult since the
clinical signs are much less specific in these age groups. Early diagnosis by
needle aspiration of the affected joint and prompt initiation of appropriate
antimicrobial therapy in conjunction with drainage of the affected joint is
critical to avoid destruction of the articular cartilage and prevent disability.
Septic arthritis in infants and children should always be managed by a
pediatrician in close consultation with an orthopedic surgeon. Empiric
antibiotic regimens should always include adequate anti-staphylococcal coverage.
Antibiotic treatment should be started with appropriate doses of intravenous
antibiotics. Switch to oral antibiotic therapy can be made when patient
demonstrates clinical improvement. A minimum of 3-4 weeks of therapy is
recommended. Close follow-up is warranted to monitor the growth of the affected
limb until skeletal maturity.
-----
J Bone Joint Surg Br. 2004 Sep;86(7):1002-6.
Seventeen-year survivorship analysis of silastic
metacarpophalangeal joint replacement.
Trail IA, Martin JA, Nuttall D, Stanley JK.
Wrightington Hospital, Wigan, England, UK.
We reviewed the records and radiographs of 381 patients with rheumatoid
arthritis who had undergone silastic metacarpophalangeal joint replacement
during the past 17 years. The number of implants was 1336 in the course of 404
operations. Implant failure was defined as either revision or fracture of the
implant as seen on radiography. At 17 years, the survivorship was 63%, although
on radiographs two-thirds of the implants were seen to be broken. Factors which
improved survival included soft-tissue balancing, crossed intrinsic transfer and
realignment of the wrist. Surgery to the thumb and proximal interphalangeal
joint had a deleterious effect and the use of grommets did not protect the
implant from fracture.
-----
Rev Med Chil. 2004 Mar;132(3):337-45.
[Total knee arthroplasty in patients with rheumatoid arthritis]
[Article in Spanish]
Amenabar PP, Carrion M, Apablaza D, Paulos J.
Departamento de Ortopedia y Traumatologia, Pontificia Universidad Catolica de
Chile, Santiago, Chile. amenabar@med.puc.cl
BACKGROUND: Approximately 90% of patients with rheumatoid arthritis (RA) will
have one or both knees involved during the course of the disease. Total knee
arthroplasty (TKA) allows restoring function and relieving pain satisfactorily,
but these patients perform in a different way than those with primary knee
osteoarthritis. AIM: To evaluate the clinical and radiographic results of TKA in
patients with RA. PATIENTS AND METHODS: We analyzed retrospectively the data of
25 posterior stabilized total knee prostheses in 19 patients, available to an
average follow-up of 6 years. The scores of Hospital for Special Surgery and of
the Knee Society were used for clinical assessment. RESULTS: The mean Hospital
for Special Surgery score increased from 44 points (range 27-58) preoperatively
to 80 points (range 58-91) at the final follow-up examination. Two prostheses
required revision and removal of the implants because of deep infection, and two
had clinical failure as defined by the Knee Society score. There were no cases
of implant loosening. DISCUSSION: Even though it is not free of complications,
TKA is a good choice in patients with RA in the medium term follow up, with 80%
of excellent and good results in our series.
-----
Rheumatology (Oxford). 2004 Mar 16
[Epub ahead of print]
Efficacy and safety
of leflunomide 10 mg versus 20 mg once daily in patients with
active rheumatoid arthritis: multinational double-blind, randomized
trial.
Poor G, Strand V.
National Institute of Rheumatology and Physiotherapy, Budapest,
Hungary, USA.
OBJECTIVE: To compare the efficacy
and safety profile of two daily maintenance doses of leflunomide,
10 mg and 20 mg, for the treatment of active rheumatoid arthritis
(RA). METHODS: In this multinational, randomized, double-blind,
parallel-group study, 402 RA patients were randomized equally
to receive daily doses of 10 mg leflunomide (n = 202; loading
dose on day 3, 100 mg) or 20 mg leflunomide (n = 200; loading
dose on day 1-3, 100 mg) for 24 weeks. The study was designed
to demonstrate non-inferiority of the efficacy of 10 mg compared
with 20 mg by calculating 95% confidence intervals for differences
in changes in tender joint count (TJC), swollen joint count (SJC)
and Health Assessment Questionnaire Disability Index (HAQ DI),
comparing these confidence intervals with predefined bounds. Results.
In the intent-to-treat population, mean improvements at the end-point
in the 10 and 20 mg groups respectively were: TJC, -7.57 and -8.89
(P = 0.061); SJC, -6.38 and -6.96 (P = 0.304); and HAQ DI, 0-0.37
and 0-0.49 (P = 0.095). By American College of Rheumatology (ACR)
>/=20% criteria, response rates were 49.8 and 56.6% respectively
(P = 0.1724). Adverse events (AEs) resulting in treatment withdrawal
were higher in the 10 mg (15.3%) than in the 20 mg treatment group
(12.0%), as were serious adverse events (SAEs): 12.9 vs 10.0%.
CONCLUSIONS: This study rejected the hypothesis of non-inferiority
of 10 mg compared with 20 mg daily maintenance doses of leflunomide.
More AEs resulting in treatment discontinuation and SAEs in patients
receiving 10 mg leflunomide daily also support a better efficacy
profile for the 20 mg daily dose.
-----
Ann Rheum Dis. 2004 Mar 5 [Epub ahead
of print]
Patient Preferences
for Treatment of Rheumatoid Arthritis.
Fraenkel L, Bogardus ST, Concato
J, Felson DT, Wittink DR.
Yale University, USA.
OBJECTIVE: To elicit rheumatoid arthritis
(RA) patient treatment preferences for DMARDs with varying risk
profiles. METHODS: Using data from published literature about
side effects, effectiveness, and cost, we ascertained patient
values for 16 DMARD characteristics. Patient preferences were
elicited using Adaptive Conjoint Analysis, an interactive computer
program that predicts preferences by asking patients to make trade-
offs between specific treatment characteristics. We ran simulations
to derive preferences for four medications representing: methotrexate,
gold, leflunomide, and etanercept, under different risk-benefit
scenarios. Infliximab was not included because it is given with
methotrexate, and we did not include preferences for combination
therapy. Based on each patient's expressed preferences, and the
characteristics of the treatments available at the time of the
study, we identified the option that best fit each patient's perspective.
RESULTS: We interviewed 120 patients (mean age 70 years). For
the base-case scenario, (which assumed the maximum benefits reported
in the literature, a low probability of adverse effects, and low
equal monthly co- pays) 95% of the respondents preferred etanercept
over the other treatment options. When all four options were described
as being equally effective, 88% continued to prefer etanercept
due to its safer short-term adverse effect profile. Increasing
etanercept's co-pay to $30.00 decreased the percent of patients
preferring this option to 80%. CONCLUSIONS: In this study, we
found that older RA patients, when asked to consider trade-offs
between specific risk and benefits, preferred etanercept over
other treatment options. Preference for etanercept is explained
by older patients' risk aversion for drug toxicity.
-----
Int J Clin Pract Suppl. 2003 Apr;(135):3-8.
Discovery, mechanisms
of action and safety of ibuprofen.
Rainsford KD.
Biomedical Research Centre, Sheffield Hallam University, Sheffield,
UK.
Ibuprofen was the product of a long
research programme during the 1950s and 1960s to develop a 'super
aspirin' for the treatment of rheumatoid arthritis which was as
effective as current alternatives but safer. Selected for development
in 1964 after several promising compounds had proved disappointing
at the clinical stage, ibuprofen was found to have a short elimination
half-life and exceptional gastrointestinal tolerability. Ibuprofen
was introduced in the United Kingdom in 1966 and in the United
States in 1974, and was the first non-steroidal anti-inflammatory
drug (NSAID) licensed for over-the-counter use in the UK in 1983
and in the US the following year. Ibuprofen is a non-cyclo-oxygenase
selective NSAID but recent evidence suggests additional anti-inflammatory
properties are due to modulation of leucocyte activity, reduced
cytokine production, inhibition of free radicals and signalling
transduction. Ibuprofen may also exert a central analgesic action
in the dorsal horn. Future roles for ibuprofen may include protection
against certain cancers and Alzheimer's disease.
-----
J Am Pharm Assoc (Wash). 2003 Mar-Apr;43(2):327-8.
New antibody approved
for treatment of rheumatoid arthritis.
Piascik P.
College of Pharmacy, University of Kentucky, Lexington, USA.
Adalimumab joins free existing biologic
agents for the treatment of RA. Its place among these therapeutic
options is unclear until head-to-head studies are performed with
adalimumab and other biologic DMARDs. Adalimumab is currently
in clinical trials for additional therapeutic uses, namely Crohn's
disease and coronary artery disease.
-----
Int J Clin Pract. 2003 Apr;57(3):231-4.
Anakinra: the first
interleukin-1 inhibitor in the treatment of rheumatoid arthritis.
Kary S, Burmester GR.
Department of Rheumatology and Immunology, Charite University
Clinic, Berlin, Germany.
Rheumatoid arthritis is an immunologically
mediated inflammation of joints of unknown aetiology and often
leads to disability. This inflammatory process may also involve
extra-articular connective tissue. New therapeutic approaches
have been made by inhibition of proinflammatory cytokines. Interleukin-1
(IL-1) is regarded as one of the most important mediators in the
development of synovialitis. In this article, anakinra (Kineret),
the first direct antagonist to IL-1, is discussed, in particular
the efficacy and safety data from clinical trials. More than 10,000
patients have been treated with anakinra with significant improvement
of inflammation and pain; the rate of radiologically visible progressive
joint damage was significantly reduced. Among the adverse events,
injection site reactions were most frequent, followed by a mild
increase in infections. No activation of tuberculosis, as in tumour
necrosis factor-alpha antagonist administration, has so far been
reported.
-----
Arthritis Rheum. 2003 Apr;48(4):927-34.
Anakinra, a recombinant
human interleukin-1 receptor antagonist (r-metHuIL-1ra), in patients
with rheumatoid arthritis: A large, international, multicenter,
placebo-controlled trial.
Fleischmann RM, Schechtman J, Bennett R, Handel ML, Burmester
GR, Tesser J, Modafferi D, Poulakos J, Sun G.
St. Paul University Hospital, Dallas, Texas 75235, USA. royfleischmann@radiantresearch.com
OBJECTIVE: To evaluate the safety
of anakinra (a recombinant human interleukin-1 receptor antagonist)
in a large population of patients with rheumatoid arthritis (RA),
typical of those seen in clinical practice. METHODS: A total of
1,414 patients were randomly assigned to treatment with 100 mg
of anakinra or placebo, administered daily by subcutaneous injection.
Background medications included disease-modifying antirheumatic
drugs, corticosteroids, and nonsteroidal antiinflammatory drugs,
alone or in combination. The primary end point was safety, which
was evaluated by adverse events (including infections), discontinuation
from study due to adverse events, and death. RESULTS: Safety was
evaluated in 1,399 patients (1,116 in the anakinra group and 283
in the placebo group; 15 patients were randomized but did not
receive any study drug) during the initial 6-month, double-blind,
placebo-controlled phase of this long-term safety study. Baseline
demographics, disease characteristics, and concomitant medications
were similar between the 2 groups. The study group included patients
with numerous comorbid conditions and a wide range of RA disease
activity. Serious adverse events occurred at a similar rate in
the anakinra group and the placebo group (7.7% and 7.8%, respectively).
Serious infectious episodes were observed more frequently in the
anakinra group (2.1% versus 0.4% in the placebo group). The rate
of withdrawal due to adverse events was 13.4% in the anakinra
group and 9.2% in the placebo group. CONCLUSION: Results from
this large, placebo-controlled safety study demonstrate that anakinra
is safe and well tolerated in a diverse population of patients
with RA, including those with comorbid conditions and those using
multiple combinations of concomitant therapies. Although the frequency
of serious infection was slightly higher in the anakinra group,
no infection was attributed to opportunistic microorganisms or
resulted in death.
-----
Arch Dis Child. 2003 Mar;88(3):186-91.
Biologic therapies for
juvenile arthritis.
Wilkinson N, Jackson G, Gardner-Medwin J.
Department of Rheumatology, Great Ormond Street Hospital, London,
UK. petherton@clara.co.uk
A group of therapies with exciting
potential has emerged for children and young people with severe
juvenile idiopathic arthritis (JIA) uncontrolled by conventional
disease modifying drugs. Theoretical understanding from molecular
biologic research has identified specific targets within pathophysiological
pathways that control rheumatoid arthritis (RA) and JIA. This
review identifies the pathways of autoimmunity to begin to show
how biologic agents have been produced to replicate, mimic, or
block culpable molecules and so promote or inhibit cellular activity
or proliferation. Of these agents, cytokine antagonists have shown
greatest promise, and early clinical studies of tumour necrosis
factor (TNF) blockade have identified dramatic clinical benefit
in many children with JIA. However, as will also be discussed,
overlap of pathways within a complex immune system makes clinical
response unpredictable and raises additional ethical and administrative
concerns.
-----
Nippon Yakurigaku Zasshi. 2003 Jan;121(1):57-64.
[Pharmacological profile
of anti-human TNF alpha monoclonal antibody, infliximab (Remicade)]
[Article in Japanese]
Sugita T.
Biology and Pharmacology Department, Discovery Research Laboratory,
Tanabe Seiyaku Co., Ltd., 3-16-89, Kashima, Yodogawa-ku, Osaka
532-8505, Japan. t-sugita@tanabe.co.jp
TNF alpha (tumor necrosis factor-alpha)
plays an important role in the pathogenesis of inflammatory diseases
including Crohn's disease and rheumatoid arthritis. Infliximab
(Remicade) is a chimeric monoclonal antibody that recognizes human
TNF alpha. Clinical trials trials have been persuasive that infliximab
is effective in both Crohn's disease and rheumatoid arthritis.
Infliximab is an important treatment option in patients with active
Crohn's disease who have not responded to conventional therapy
and in patients with Crohn's disease who have fistulae. Moreover,
infliximab plus methotrexate is effective in patients with active
rheumatoid arthritis who have not responded adequately to traditional
disease-modifying anti-rheumatic drugs, in terms of reducing symptoms
and signs, inhibiting the progression of structural damage and
improving physical function.
-----
Manag Care Interface. 2003 Mar;16(3):44-50,
55.
Assessing the value
of rheumatoid arthritis treatment alternatives: the potential
effect of
tumor necrosis factor inhibitors.
Mizutani W.
Talbert Medical Group, Fountain Valley, California, USA. mizutaniw@prodigy.net
Early intervention with drugs that
delay structural damage from rheumatoid arthritis may limit disability
and reduce the high costs associated with advancing disease. However,
conventional agents have a potential for significant toxicities,
which require monitoring that confers additional treatment costs.
A new class of drugs has been developed: biologic response modifiers,
two of which--etanercept and infliximab--inhibit tumor necrosis
factor, a pivotal regulator of inflammation, and delay arthritic
progression. Managed care organizations should encourage early
diagnosis of rheumatoid arthritis, referral to a rheumatologist,
and treatment with agents that reduce the overall costs of this
debilitating disease.
-----
J Pain Symptom Manage. 2003 Feb;25(2
Suppl):S6-20.
Advances in rheumatology:
coxibs and beyond.
Kuritzky L, Weaver A.
Department of Community Health and Family Medicine, University
of Florida, Gainesville, FL 32608, USA.
Arthritis is a growing health concern
in the US with approximately 70 million Americans currently affected.
This figure will inevitably rise as the population ages. The pain
and decreased mobility associated with arthritis have a significant
impact on quality of life and because patients with arthritis
are less active than the general population, they are at risk
of additional conditions such as obesity, heart disease, diabetes,
and hypertension. There are currently no disease modifying osteoarthritis
(OA) drugs available; therefore anti-inflammatory, and/or analgesic
medications such as acetaminophen and NSAIDs and simple analgesics
form the mainstay of treatment. Coxibs may be preferred to traditional
NSAIDs because of their improved gastrointestinal (GI ) safety
and tolerability profile. The use of topical agents may also be
beneficial in some patients. In rheumatoid arthritis (RA) where
disease modifying drugs (DMARDs) are available, anti-inflammatory
agents such as NSAIDs and coxibs are used as adjuncts to disease
modifying therapy. However, patients with RA are at increased
risk of NSAID-related GI injury, particularly if they are also
on corticosteroid medication. Pharmacological treatment of both
RA and OA should be combined with appropriate nonpharmacological
modalities such as patient education, exercise programs, and joint
motion and strengthening exercises. Such activities may delay
joint degradation and help maintain physical function.
-----
Scand J Rheumatol. 2003;32(2):83-8.
Reumacon (CPH82) showed
similar x-ray progression and clinical effects as methotrexate
in a two year comparative study on patients with early rheumatoid
arthritis.
Svensson B, Pettersson H.
Section of Rheumatology, Department of Medicine, Helsingborg's
lasarett, Helsingborg, Sweden. bjoern.svensson@swipnet.se
OBJECTIVES: To study x-ray development
and clinical effects, tolerability and safety after 2 years treatment
of RA patients with Reumacon (CPH82) or methotrexate (MTX). PATIENTS
AND METHODS: This study is a 74 week open continuation of a 24
week double blind comparison of 100 patients with early RA (disease
duration less than 2 years) treated either with Reumacon or MTX.
RESULTS: The mean Larsen scores and the mean number of erosions
increased significantly from baseline to 24 weeks and from 24
weeks to endpoint in both groups with no significant difference
between them. Both groups had improved significantly in all clinical
variables after 24 weeks and this improvement was sustained after
two years. CONCLUSIONS: Radiological progression in patients treated
with CPH82 was similar to that in patients treated with MTX. The
clinical effect of the two drugs was sustained over the two year
trial in both treatment groups.
-----
Instr Course Lect. 2003;52:163-74.
Metacarpophalangeal
joint arthroplasty in rheumatoid arthritis.
Kimball HL, Terrono AL, Feldon P, Zelouf DS.
Tufts University, Department of Orthopaedics, New England Baptist
Bone and Joint Institute, New England Baptist Hospital, Boston,
Massachusetts, USA.
In patients with rheumatoid arthritis,
metacarpophalangeal joint deformities can significantly affect
hand function. Flexible hinge implant arthroplasty, designed in
the 1960s, remains the most accepted and widely performed technique
for treatment of severely involved metacarpophalangeal joints
in rheumatoid arthritis. An arc of motion of 40 degrees to 60
degrees can be expected after arthroplasty, with improvement of
finger extension and ulnar deviation. Silicone implant arthroplasty,
although technically challenging, is the standard surgical procedure
for improving hand function in these patients. Complications include
recurrent ulnar deviation, extensor lag, implant fracture, infection,
and silicone-induced particulate synovitis. Despite these limitations,
patient satisfaction is high with enhancement of hand appearance
and function and relief of pain.
-----
J Bone Joint Surg Br. 2003 Apr;85(3):347-50.
Treatment of primary
degenerative arthritis of the elbow by ulnohumeral arthroplasty.
A long-term follow-up.
Phillips NJ, Ali A, Stanley D.
Shoulder and Elbow Unit, Northern General Hospital, Sheffield,
England, UK.
Between 1990 and 1996 we performed
20 consecutive ulnohumeral arthroplasties for primary osteoarthritis
of the elbow. The outcome was assessed using the Disabilities
of Arm, Shoulder and Hand Score (DASH) and the Mayo Elbow Performance
Score (MEPS) at a mean follow-up of 75 months (58 to 132). There
were excellent or good results in 17 elbows (85%) using the DASH
score and in 13 (65%) with the MEPS (correlation coefficient 0.79).
The mean fixed flexion deformity had improved by 10 degrees and
the range of flexion by a mean of 20 degrees. In 16 elbows (80%)
the benefits of surgery had been maintained, and of 16 patients
working at the time of operation, 12 (75%) had returned to the
same job. There was no correlation between radiological recurrence
of degenerative changes and the amount of fixed flexion deformity,
the flexion arc, or the elbow scores.
-----
J Bone Joint Surg Br. 2003 Apr;85(3):354-7.
Total elbow replacement
using the Kudo prosthesis. Clinical and radiological review with
five- to seven-year follow-up.
Potter D, Claydon P, Stanley D.
Northern General Hospital NHS Trust, Sheffield, England, UK.
Between 1993 and 1996, we undertook
35 Kudo 5 total elbow replacements in a consecutive series of
31 rheumatoid patients. A total of 25 patients (29 procedures)
was evaluated at a mean follow-up of six years (5 to 7.5) using
the Mayo Clinic performance index. In addition, all patients were
assessed for loosening using standard anteroposterior and lateral
radiographs. At review, 19 elbows (65%) had either no pain or
mild pain, ten (35%) had moderate pain and none had severe pain.
The mean arc of flexion/extension was 94 degrees (35 to 130) and
supination/pronation was 128 degrees (30 to 165). A fracture of
the medial epicondyle occurred during surgery in one patient.
This was successfully treated with a single AO screw and a standard
Kudo 5 implant was inserted. Postoperatively, there were no infections.
One patient had a dislocation which was treated by closed reduction
and five had neurapraxia of the ulnar nerve. Radiologically, there
was no evidence of loosening of the humeral component, but two
ulnar components had progressive radiolucent lines suggestive
of loosening. Two other ulnar components had incomplete and non-progressive
radiolucent lines. With definite radiological loosening as the
endpoint, the probability of survival of the Kudo 5 prosthesis
at five years using the Kaplan-Meier method was 89%.
-----
Int J Clin Pract Suppl. 2003 Apr;(135):9-12.
A general overview of
the use of ibuprofen in paediatrics.
Autret-Leca E.
Tours University Hospital, France.
Ibuprofen is prescribed for children
for the treatment of acute pain and fever, and for juvenile idiopathic
arthritis. The pharmacokinetic characteristics of ibuprofen in
children are similar to those in adults and the relationship between
dose and response is linear over the range 5-10 mg/kg. Clinical
trials of ibuprofen have shown the effective dose range to be
7.5-10 mg/kg. The maximum reduction in temperature occurs 3-4
hours after administration. In comparative clinical trials, ibuprofen
has been shown to be equally as effective as or more effective
than paracetamol as an analgesic and antipyretic and to have a
longer duration of action; it is also as effective as aspirin.
The adverse effects of ibuprofen are similar to those of other
non-steroidal anti-inflammatory drugs but clinical experience
suggests that ibuprofen is better tolerated by children than adults
and it is safer in overdose than paracetamol and aspirin.
-----
Chir Main. 2003 Feb;22(1):30-6.
[Guepar anatomical trapeziometacarpal
prosthesis]
[Article in French]
Masmejean E, Alnot JY, Chantelot C, Beccari R.
Hopital europeen Georges-Pompidou (HEGP), service de chirurgie
de la main et du membre superieur (Pr J.-P. Lemerle), 20, rue
Leblanc, 75908 Paris, France. emmanuel.masmejean@hop.egp.ap-hop-paris.fr
INTRODUCTION: A choice of surgical
techniques of treatment for trapeziometacarpal (TMC) Osteo-Arthritis
(OA) have been described. Total arthroplasty is often used, especially
in France. Many papers have been published, presenting various
prostheses. In English literature, this device is not thoroughly
used. MATERIALS ET METHODS: Guepar total arthroplasty is a cemented
ball-in-socket prosthesis in metal-polyethylene. It includes an
anatomical stem available in 4 sizes. After failure of the conservative
treatment, total arthroplasty must be reserved to elderly patients,
painful, with OA Dell stage III or IV aligned or not. The trapezial
height must be sufficient. The authors reports the preliminary
results of 64 Guepar prostheses, anatomical new design, implanted
since 1995. RESULTS: Results of 63 prostheses are presented. One
removal had been necessary at 9 months for metacarpal loosening
(failure). Mean follow-up was 29 months. Clinical results were
judged excellent or good in all cases. Regarding the radiological
results, no modifications has been observed in 56 cases. Six radiolucent
lines without displacement of the implants has been noted, with
no incidence on clinical results. In one case, a metacarpal stem
penetrated into the medullary canal in the bone axis but without
any clinical modifications. DISCUSSION AND CONCLUSION: Clinically,
in addition to pain relief, trapeziometacarpal prosthesis allows
to preserve the first column length and to obtain a better opposition
of the thumb as well of a better thumb-digits pinch, compared
after trapeziectomy. Radiologically, as for total hip arthroplasty,
the exact adaptation of an anatomical stem (new design) to the
canal has probably a better prognosis at long term follow-up.
-----
Int J Technol Assess Health Care.
2003 Winter;19(1):41-56.
Efficacy and safety
of viscosupplementation with Hylan G-F 20 for the treatment of
knee osteoarthritis:
a systematic review.
Espallargues M, Pons JM.
Catalan Agency for Health Technology Assessment and Research,
Barcelona, Spain. mespa@olimpia.scs.es
OBJECTIVES: To review the scientific
evidence on the efficacy, effectiveness, and safety of intra-articular
injections of Hylan G-F 20 for the treatment of knee osteoarthritis.
METHODS: Systematic review of experimental and observational studies
performed in humans up to December 1999. Qualitative and quantitative
(meta-analytic) techniques were used for data synthesis. RESULTS:
A single course of intra-articular Hylan G-F 20 provides a statistically
significant and clinically relevant short-term decrease of the
painful symptomatology of knee osteoarthritis and improves joint
function. It also seems to delay the need for knee replacement,
if results observed in noncontrolled studies are confirmed. Hylan
G-F 20 has a comparable efficacy to that of oral NSAID, and a
smaller risk of gastrointestinal adverse effects. It seems to
be well tolerated and safe, but the short follow-up in most studies
limits any extrapolation of the effectiveness and safety over
the longer term. There is also scarce evidence on the effect of
multiple courses of Hylan G-F 20, and the scientific rigor of
both experimental and nonexperimental studies reviewed is somewhat
limited. CONCLUSIONS: Whereas there is good quality scientific
evidence showing that Hylan G-F 20 is a safe and well-tolerated
therapy providing a short-term decrease of the pain symptoms while
improving joint function, the delay of the need for knee replacement
as well as the durability of the effect over the longer term have
only been demonstrated in noncontrolled clinical series. The available
evidence is not sufficient to reach firm conclusions on the effect
of multiple courses of intra-articular injections of Hylan G-F
20 on health outcomes.
-----
J Am Acad Orthop Surg. 2003 Jan-Feb;11(1):12-24.
Rheumatoid arthritis
of the shoulder.
Chen AL, Joseph TN, Zuckerman JD.
Department of Orthopaedic Surgery, New York University-Hospital
for Joint Diseases, New York, NY, USA.
Rheumatoid arthritis affecting the
shoulder region is a progressive disorder that results in pain,
loss of range of motion, and functional disability. The inflammatory
response, which is of unknown etiology, results in synovitis,
pannus formation, and articular destruction. Even when patient
history and physical examination suggest rheumatoid involvement
of the shoulder, laboratory assessment and radiographic evaluation
often are necessary to establish the diagnosis. Nonsurgical management
is the primary treatment, including pharmacologic and physical
therapy regimens for patients with mild symptoms and functional
disability. Surgical intervention is indicated in patients with
significant pain and functional limitation when nonsurgical treatment
fails to provide relief. The procedure selected depends on careful
assessment of the degree of articular cartilage injury and compromise
of the periarticular soft tissues.
-----
Ann Rheum Dis. 2003 May;62(5):482-6.
Toxicity profiles of
traditional disease modifying antirheumatic drugs for rheumatoid
arthritis.
Aletaha D, Kapral T, Smolen JS.
Division of Rheumatology, Department of Internal Medicine III,
University of Vienna, Austria. Daniel.Aletaha@akh-wien.ac.at
BACKGROUND: The progression of rheumatoid
arthritis (RA) can be retarded or halted by disease modifying
antirheumatic drugs (DMARDs). Next to inefficacy, toxicity limits
their use. OBJECTIVE: To explore the toxicity profiles of DMARDs
in daily life. PATIENTS AND METHODS: Five hundred and ninety three
patients with RA charts (>2300 patient years of treatment)
were reviewed at two rheumatology outpatient clinics. All recorded
data on toxicity and reasons for stopping treatment were collected.
RESULTS: Adverse events were common reasons for treatment discontinuation
(42% of treatments). In 70% they were subjectively reported at
the clinical visit, while substantial laboratory abnormalities
were seen relatively rarely (9% of treatments: abnormal liver
function tests in 5%; haematological abnormalities in 3%; impaired
renal function in 1%). No single case of retinopathy from antimalarial
drugs (that is, an incidence of <0.3 events/1000 patient years)
was found, although eye examinations by the specialists were abnormal
30 times per 1000 patient years, mostly revealing keratopathy.
Most commonly reported symptoms per 1000 patient years were nausea
(54 events), abdominal pain (37 events), and rashes (34 events).
Adverse events were more likely to occur with increasing number
of consecutive DMARD courses. CONCLUSION: The first DMARD course
in a patient seems to be safer than the consecutive ones. In addition,
the incidence of adverse events (AEs) seems to be similar for
high and low dose treatment. Data are also provided on types and
incidence of AEs that are consistent with previous studies in
other countries and different settings.
-----
Med Arh. 2003;57(1):59-60.
[Use of TENS in patients
with rheumatoid arthritis]
[Article in Serbo-Croatian (Roman)]
Ostojic L, Ostojic Z, Bucek I, Busic I, Miljanovic V, Ivelja D.
Medicinski fakultet Sveucilista u Mostaru, KB Mostar.
The patients with rheumatoid arthritis
of the fourth grade have used the whole basic therapy and, of
course, antirheumatic therapy with all their positive and negative
effects. We have applied and analysed the application of analgetic
physical therapy with TENS (Transcutaneous Electrical Nerve Stimulation).
TENS appeared to be a perfect substitution for nonsteroid antirheumatics
and analgetics. Its easy application, the possibility of using
at home and practically non-existent contraindications give him
the priority at pain relief for rheumatoid arthritis of the fourth
grade.
-----
Can J Surg. 2003 Apr;46(2):103-10.
Trapezial arthroplasty
with silicone rubber implantation for advanced osteoarthritis
of the trapeziometacarpal joint of the thumb.
MacDermid JC, Roth JH, Rampersaud YR, Bain GI.
Hand and Upper Limb Centre, Clinical Research Laboratory, University
of Western Ontario, London, Ont. jmacderm@.uwo.ca
INTRODUCTION: Arthritis in the trapeziometacarpal
joint of the thumb can cause swelling and loss of motion. Treatment
options include arthrodesis, replacement arthroplasty and interposition
arthroplasty. Our objective in this clinical study was to determine
outcomes after trapezial arthroplasty with a silicone rubber implant
and the relationship between self-reported and measured outcomes.
METHODS: At the Hand and Upper Limb Centre, St. Joseph's Hospital,
London, Ont., a tertiary care centre, we reviewed a series of
26 patients with advanced osteoarthritis who underwent silicone
rubber trapezial arthroplasty. The follow-up averaged 6.5 years.
We assessed the outcomes subjectively, and by clinical, functional
and radiographic examination. RESULTS: Although 88% of patients
reported some improvement in pain and satisfaction, when quantified
the improvement was less impressive: only 5.7 (on a visual analogue
scale of 1-10, poor-excellent) for pain and 5.6 for satisfaction.
Superior subjective results were reported by patients older than
60 years. Osteoarthritic changes had caused pronounced functional
impairment in the hands of patients who underwent surgery and
those who did not, so that any long-term benefit of surgery was
not measurable. Patients had difficulty manipulating both small
and large objects on the Jebsen's hand function test. Peri-implant
and carpal radiographic lytic changes were observed in 90% of
patients. Six patients (20%) required revision surgery (3 early,
3 late), including 1 with a pathologic scaphoid fracture. CONCLUSIONS:
Although clinical, functional and radiographic results were poor,
they did not predict either satisfaction or pain improvement reported
by patients, illustrating the need for a comprehensive standardized
outcome evaluation to make informed decisions on the value of
surgical intervention for osteoarthritis of the trapeziometacarpal
joint.
-----
Instr Course Lect. 2003;52:383-96.
Allograft meniscal transplantation:
background, techniques, and results.
Cole BJ, Carter TR, Rodeo SA.
Department of Orthopedics, Rush University, Chicago, Illinois,
USA.
In the early arthritic knee, meniscal
allograft transplantation alleviates pain and provides for a measurable
improvement in functional level in appropriately selected postmeniscectomy
patients. The allograft heals readily to the host, develops a
normal appearance, and repopulates with the host cells. The allograft
functions similarly to autograft tissue in its load-sharing properties.
Theoretically, restoration of normal meniscal anatomy should decelerate
or prevent further degenerative changes; however, this particular
indication remains investigational. Basic science and clinical
results support the intermediate-term efficacy of allograft meniscus
transplantation in symptomatic meniscectomized patients as long
as relevant comorbidities are corrected and significant coexisting
arthritis is absent. Excellent pain relief and improved function
can be achieved when rigid indications are adhered to.
-----
Arthritis Rheum. 2003 Apr;48(4):1093-101.
Efficacy of etanercept
for the treatment of juvenile idiopathic arthritis according to
the onset type.
Quartier P, Taupin P, Bourdeaut F, Lemelle I, Pillet P, Bost M,
Sibilia J, Kone-Paut I, Gandon-Laloum S, LeBideau M, Bader-Meunier
B, Mouy R, Debre M, Landais P, Prieur AM.
Hopital Necker-Enfants Malades, Paris, France. quartier@necker.fr
OBJECTIVE: To assess the efficacy
of etanercept in patients with juvenile idiopathic arthritis (JIA),
and to assess the tolerance of these patients to etanercept. METHODS:
All JIA patients with active chronic polyarthritis, who were first
treated with etanercept between November 1999 and June 2001 in
18 French centers because of poor response or intolerance to methotrexate,
were included in this open-label, prospective, multicenter study.
A standardized questionnaire was sent to the treating physicians.
We assessed the validated international core-set score for JIA
activity every 3 months and performed an intent-to-treat analysis.
We also compared the risk of treatment failure in patients defined
as having systemic-onset, oligoarticular-onset, or polyarticular-onset
JIA. RESULTS: Sixty-one patients were enrolled and were followed
up for a median of 13 months. Treatment had to be stopped in 1
patient who became pregnant and in 12 patients due to severe side
effects, including neurologic or psychiatric disorders, retrobulbar
optic neuropathy, major weight gain, severe infection, cutaneous
vasculitis with systemic symptoms, hemorrhagic diarrhea, uveitis
flare, and pancytopenia. All of these side effects disappeared
after discontinuation of etanercept. Crohn's disease was subsequently
diagnosed in 1 child. Scores improved by > or =30% in 73% of
patients after 3 months, but this proportion decreased to 39%
after 12 months. The response rate was significantly lower in
patients with systemic-onset JIA than in those with oligoarticular-
or polyarticular-onset JIA. CONCLUSION: Treatment of JIA with
etanercept may be associated with a wide spectrum of severe side
effects. Although most patients initially respond to etanercept,
this initial response is not always followed by sustained improvement
over longer periods of time. In addition, the higher rate of treatment
failure in the group with systemic-onset JIA indicates that these
patients in particular may require alternative treatments.
-----
Rev Med Interne. 2003 Feb;24(2):123-6.
[Inhibitors of TNFalpha]
[Article in French]
Brousse C.
Service de rhumatologie, hopital Foch, 40, rue Worth, 92150, Suresnes,
France. c.brousse@hopital-foch.org <c.brousse@hopital-foch.org>
INTRODUCTION: TNFalpha inhibitors
etanercept and infliximab, are a new and very exciting drugs.
Etanercept is administered subcutaneously, and infliximab by intravenous
perfusions. EXEGESIS: They are indicated in severely rheumatoid
arthritis resistant to treatment with methotrexate, and in Crohn's
disease refractory to immunosuppressive agents. Their safety profile
is good, but the risk of infections is increased. CONCLUSION:
Their indication in other inflammatory diseases need further studies.
-----
Rheum Dis Clin North Am. 2003 Feb;29(1):37-59,
vi.
Reactive arthritis:
newer developments.
Flores D, Marquez J, Garza M, Espinoza LR.
Section of Rheumatology, Department of Medicine, Louisiana State
University Health Sciences Center, 1542 Tulane Avenue, New Orleans,
LA 70112-2822, USA.
Reactive arthritis (ReA) is characterized
by an aseptic inflammatory articular involvement occurring in
a genetically predisposed individual secondary to an infectious
process localized outside the joint. ReA usually refers to an
acute or insidious oligoarthritis process after enteric (enteroarthritis)
or urogenital (uroarthritis) infection. Conventional antirheumatic
therapeutic modalities based on nonsteroid anti-inflammatory drugs,
sulfasalazine, and steroids are effective in the majority of patients.
In more refractory cases, the use of second-line agents including
methotrexate and more recently biological agents such as etanercept
and infliximab has been found highly effective. The role of antibiotics
remains not well established, although they appear to be effective
in acute ReA of urogenital origin.
-----
Ann Rheum Dis. 2003 Apr;62(4):291-6.
Cyclosporin A monotherapy
versus cyclosporin A and methotrexate combination therapy in patients
with early rheumatoid arthritis: a double blind randomised placebo
controlled trial.
Gerards AH, Landewe RB, Prins AP, Bruijn GA, Goei The HS, Laan
RF, Dijkmans BA.
VU Medical Centre and Jan van Breemen Instituut, Amsterdam, The
Netherlands. agerards@SSVZ.nl
OBJECTIVE: To compare the efficacy
and toxicity of cyclosporin A (CsA) monotherapy with CsA plus
methotrexate (MTX) combination therapy in patients with early
rheumatoid arthritis (RA). PATIENTS AND METHODS: 120 patients
with active RA, rheumatoid factor positive and/or erosive, were
randomly allocated to receive CsA with MTX (n=60) or CsA with
placebo (n=60). Treatment with CsA was started in all patients
at 2.5 mg/kg/day and increased to a maximum of 5 mg/kg/day in
16 weeks. MTX was started at 7.5 mg/week and increased to a maximal
dose of 15 mg/week at week 16. Primary outcomes were clinical
remission (Pinals criteria) and radiological damage (Larsen score),
at week 48. RESULTS: Treatment was discontinued prematurely in
27 patients in the monotherapy group (21 because of inefficacy,
and six because of toxicity) and in 26 patients in the combination
therapy group (14 and 12, respectively). At week 48, clinical
remission was achieved in four patients in the monotherapy group
and in six patients in the combination therapy group (p=0.5).
The median Larsen score increased to 10 (25th, 75th centiles:
3.5; 13.3) points in the monotherapy group and to 4 (1.0; 10.5)
points in the combination therapy group (p=0.004). 28/60 (47%)
of patients in the monotherapy group v 34/60 (57%) of patients
in the combination therapy group had reached an American college
of Rheumatology 20% (ACR20) response (p=0.36) at week 48; 15/60
(25%) v 29/60 (48%) of patients had reached an ACR50 response
(p=0.013); and 7 (12%) v 12 (20%) of patients had reached an ACR70
response (p=0.11).Their was a tendency towards more toxicity in
the combination therapy group. CONCLUSIONS: In patients with early
RA, neither CsA plus MTX combination therapy nor CsA monotherapy
is very effective in inducing clinical remission. Combination
therapy is probably better at improving clinical disease activity,
and definitely better at slowing radiological progression. Combination
therapy should still be compared with methotrexate monotherapy.
-----
Aliment Pharmacol Ther. 2003 Feb 15;17(4):489-501.
Review article: The
pharmacological properties and clinical use of valdecoxib, a new
cyclo-oxygenase-2-selective inhibitor.
Alsalameh S, Burian M, Mahr G, Woodcock BG, Geisslinger G.
Out-patient Clinic for Rheumatic Diseases, Marburg, Germany.
Cyclo-oxygenase-2-selective inhibitors
produce less gastric damage than conventional non-steroidal anti-inflammatory
drugs. Valdecoxib is a new orally administered cyclo-oxygenase-2-selective
inhibitor, recently approved for use in osteoarthritis, rheumatoid
arthritis and primary dysmenorrhoea in the USA. The drug has been
evaluated in more than 60 clinical studies involving more than
14 000 patients and healthy volunteers. The analgesic efficacy
of valdecoxib at a dose of 10 mg once daily in both osteoarthritis
and rheumatoid arthritis is superior to that of placebo and similar
to that of traditional non-steroidal anti-inflammatory drugs.
Valdecoxib is effective in single doses of up to 40 mg for the
alleviation of acute menstrual pain and has a rapid onset of action
(within 30 min) and a long duration of analgesia (up to 24 h).
Valdecoxib is well tolerated and has safety advantages compared
with traditional non-steroidal anti-inflammatory drugs in terms
of less gastrointestinal toxicity and a lack of an effect on platelet
function. The incidence of adverse effects involving the kidney
(fluid retention, oedema and hypertension) is similar to that
of non-selective, non-steroidal anti-inflammatory drugs.
-----
Arch Dis Child. 2003 Mar;88(3):192-6.
Intra-articular corticosteroid
injections in juvenile idiopathic arthritis.
Cleary AG, Murphy HD, Davidson JE.
Royal Liverpool Children's Hospital, Eaton Road, Liverpool L12
2AP, UK. gavin.cleary@talk21.com
Therapeutic intervention with intra-articular
steroid injections in juvenile idiopathic arthritis (JIA) has
evolved from experience with adults with inflammatory joint disease,
with the earliest report being published in 1951. The technique
has subsequently been introduced into paediatric rheumatology
practice, although much of the evidence supporting its use remains
anecdotal or based on open, non-controlled studies. This review
examines the body of evidence relating to many aspects of treating
children with JIA with intra-articular steroids, and is approached
from both a medical and a physiotherapy perspective. Where appropriate,
important areas for future research are identified and discussed.
-----
Arthritis Rheum. 2003 Feb;48(2):370-7.
Safety and efficacy
of long-term intraarticular steroid injections in osteoarthritis
of the knee: a randomized, double-blind, placebo-controlled trial.
Raynauld JP, Buckland-Wright C, Ward R, Choquette D, Haraoui B,
Martel-Pelletier J, Uthman I, Khy V, Tremblay JL, Bertrand C,
Pelletier JP.
Hopital Notre-Dame, Centre Hospitalier de l'Universite de Montreal,
Montreal, Quebec, Canada. jp.raynauld@videotron.ca
OBJECTIVE: To evaluate the safety
and efficacy of long-term intraarticular (IA) steroid injections
for knee pain related to osteoarthritis (OA). METHODS: In a randomized,
double-blind trial, 68 patients with OA of the knee received IA
injections of triamcinolone acetonide 40 mg (34 patients) or saline
(34 patients) into the study knee every 3 months for up to 2 years.
The primary outcome variable was radiologic progression of joint
space narrowing of the injected knee after 2 years. Measurements
of minimum joint space width were performed by an automated computerized
method on standardized fluoroscopically guided radiographs taken
with the patient standing and with the knee in a semiflexed position.
The clinical efficacy measure of primary interest was the pain
subscale from the Western Ontario and McMaster Universities OA
Index (WOMAC). Efficacy measures of secondary interest were the
total score on the WOMAC, physician's global assessment, patient's
global assessment, patient's assessment of pain, range of motion
(ROM) of the affected knee, and 50-foot walking time. Clinical
symptoms were assessed just before each injection. RESULTS: At
the 1-year and 2-year followup evaluations, no difference was
noted between the two treatment groups with respect to loss of
joint space over time. The steroid-injected knees showed a trend
toward greater symptom improvement, especially at 1 year, for
the WOMAC pain subscale, night pain, and ROM values (P = 0.05)
compared with the saline-injected knees. Using area under the
curve analyses, knee pain and stiffness were significantly improved
throughout the 2-year study by repeated injections of triamcinolone
acetonide, but not saline (P < 0.05). CONCLUSION: Our findings
support the long-term safety of IA steroid injections for patients
with symptomatic knee OA. No deleterious effects of the long-term
administration of IA steroids on the anatomical structure of the
knee were noted. Moreover, long-term treatment of knee OA with
repeated steroid injections appears to be clinically effective
for the relief of symptoms of the disease.
-----
Arthritis Rheum. 2003 Apr 15;49(2):216-20.
Declining use of orthopedic
surgery in patients with rheumatoid arthritis? Results of a long-term,
population-based assessment.
da Silva E, Doran MF, Crowson CS, O'Fallon WM, Matteson EL.
Universidade Federale de Sao Paulo, Brazil.
OBJECTIVE: To describe the use of
orthopedic surgery, including joint replacement surgery, in a
well-defined, population-based cohort of patients with rheumatoid
arthritis (RA) and to identify characteristics that predict such
use. METHODS: A retrospective medical record review was performed
of cases of RA incident in Rochester, Minnesota, during the years
1955-1995. All joint surgeries were recorded. RESULTS: Of the
total 609 RA incident cases, 242 patients underwent 1 or more
(maximum of 20/patient) surgical procedures involving joints during
their followup. Overall, this RA cohort had 7.4 surgeries per
100 person-years of followup; the cumulative incidence for joint
surgery for RA-related joint disease at 30 years was 33.7% +/-
SEM 3.8%. The risk of having a disease-related joint surgery for
RA is increased in patients who are women, younger, positive for
rheumatoid factor, and have rheumatoid nodules. When adjusted
for duration of followup, patients with RA diagnosed after 1985
were significantly less likely to have undergone joint surgery
for RA (P < 0.001). Survival of patients who underwent total
joint arthroplasty was similar to those who did not. CONCLUSION:
Reconstructive surgeries are common in RA, although patients diagnosed
after 1985 are less likely to require joint surgery. These findings
may reflect trends in medical disease management and have importance
for health care resource utilization planning.
-----
Pol Arch Med Wewn. 2002 Nov;108(5):1055-63.
[Analysis of efficacy
and safety of multiple intravenous infusion of anti-tumor necrosis
factor-alpha monoclonal antibody (Remicade) combined with methotrexate
compared with sodium aurothiomalate and intramuscular depot methylprednisolone
in rheumatoid arthritis]
[Article in Polish]
Wiland P, Glowska A, Chlebicki A, Szechinski J.
Oddzial Chorob Wewnetrznych i Reumatologii Okregowego Szpitala
Kolejowe, Wroclawiu.
The objective of the paper was compare
the effects and tolerability of combined therapy of multiple intravenous
infusions of anti-tumour necrosis factor-alfa (TNF-alfa) monoclonal
antibody (Remicade) with methotrexate versus treatment with sodium
aurothiomalate and intramuscular depot methylprednisolone in rheumatoid
arthritis (RA). We investigate also the interval necessary to
obtain the improvement in both treatment groups. 36 patients commencing
intramuscular sodium aurothiomalate therapy with intramuscular
depot methylprednisolone acetate at weeks 0, 4, 8 and 12 in addition
to chrysotherapy were compared in retrospective analysis with
32 patients starting with multiple intravenous infusions of infliximab,
anti-TNF-alfa monoclonal antibody (Remicade) and methotrexate
at a stable dose. Patients were assessed by composite clinical
score (DAS 28) and C-reactive protein during 22 weeks of therapy.
At week 2 and 6 a significantly greater percentage of infliximab-treated
than gold-treated RA patients achieved improvement in each clinical
measurement of disease activity. At 22 week of treatment moderate
and good response according to EULAR criteria was achieved in
91% of infliximab-treated patients and 58% gold treated patients
(p < 0.001). Adverse events were more frequently observed in
infliximab-treated patients, but only gold-treated patients discontinued
treatment because adverse events (2 patients due to proteinuria,
2 patients due to mucocutaneous changes and one patient due to
leucopenia). The higher percentage of adverse events in infliximab-treated
patients was caused mainly by the occurrence of infusion reactions
(23 reactions out of 160 infusions); most of them were mild (somnolentia
and headache) and transient. Viral infections (including herpes
simplex and zoster) were more common in patients treated with
infliximab and methotrexate. Combination therapy of infliximab
and methotrexate is more effective in reducing clinical and biochemical
disease activity than gold with methylprednisolone treatment in
RA patients during 22 weeks of treatment, especially in the first
6 weeks.
-----
Rev Med Univ Navarra. 2002 Jul-Sep;46(3):23-7.
[Levofloxacin. Clinical
experience with long-term treatment of osteoarticular infections]
[Article in Spanish]
Azanza JR, Cardenas E, Munoz MJ, Valenti JR, Garcia-Quetglas E.
Servicio de Farmacologia Clinica, Clinica Universitaria, Facultad
de Medicina, Universidad de Navarra, Avda. Pio XII, 36. 31080
Pamplona.
We evaluated the efficacy and safety
profile of the long-term administration of levofloxacin in osteoarticular
infections. For this purpose, 50 patients were included during
the years 1999 to 2001 on an initial estimation to be under treatment
with this antibiotic for at least 4 weeks. Forty six percent (46%)
of patients were male and received treatment during a mean-time
of 122.8 days. In forty one of a total of forty nine evaluable
patients (83.7%) outcome was considered satisfactory with a total
recovery or improvement of disease. Clinical and analytical series
of examinations were performed, with no significant abnormalities
being observed. Five (5) patients presented a total of 7 adverse
events: gastrointestinal intolerance (3), oral mycosis (1), petechia
(1), parestesia (1) and pruriginous rash(1). Only in three cases
interruption of therapy was considered necessary. In conclusion,
levofloxacin presents an adequate efficacy and is a well-tolerated
therapy; both characteristics make it an appropriate treatment
for those infections that require long-term therapy.
-----
Arthritis Rheum. 2002 Feb;46(2):347-56.
COBRA combination therapy
in patients with early rheumatoid arthritis: long-term structural
benefits of a brief intervention.
Landewe RB, Boers M, Verhoeven AC, Westhovens R, van de Laar MA,
Markusse HM, van Denderen JC, Westedt ML, Peeters AJ, Dijkmans
BA, Jacobs P, Boonen A, van der Heijde DM, van der Linden S.
Department of Internal Medicine/Rheumatology, PO Box 5800, University
Hospital Maastricht, 6202 AZ Maastricht, The Netherlands. RLAN@SINT.AZM.NL
OBJECTIVE: The Combinatietherapie
Bij Reumatoide Artritis (COBRA) trial demonstrated that step-down
combination therapy with prednisolone, methotrexate, and sulfasalazine
(SSZ) was superior to SSZ monotherapy for suppressing disease
activity and radiologic progression of rheumatoid arthritis (RA).
The current study was conducted to investigate whether the benefits
of COBRA therapy were sustained over time, and to determine which
baseline factors could predict outcome. METHODS: All patients
had participated in the 56-week COBRA trial. During followup,
they were seen by their own rheumatologists and were also assessed
regularly by study nurses; no treatment protocol was specified.
Disease activity, radiologic damage, and functional ability were
the primary outcome domains. Two independent assessors scored
radiographs in sequence according to the Sharp/van der Heijde
method. Outcomes were analyzed by generalized estimating equations
on the basis of intent-to-treat, starting with data obtained at
the last visit of the COBRA trial (56 weeks after baseline). RESULTS:
At the beginning of followup, patients in the COBRA group had
a significantly lower mean time-averaged 28-joint disease activity
score (DAS28) and a significantly lower median radiologic damage
(Sharp) score compared with those in the SSZ monotherapy group.
The functional ability score (Health Assessment Questionnaire
[HAQ]) was similar in both groups. During the 4-5 year followup
period, the time-averaged DAS28 decreased 0.17 points per year
in the SSZ group and 0.07 in the COBRA group. The Sharp progression
rate was 8.6 points per year in the SSZ group and 5.6 in the COBRA
group. After adjustment for differences in treatment and disease
activity during followup, the between-group difference in the
rate of radiologic progression was 3.7 points per year. The HAQ
score did not change significantly over time. Independent baseline
predictors of radiologic progression over time (apart from treatment
allocation) were rheumatoid factor positivity, Sharp score, and
DAS28. CONCLUSION: An initial 6-month cycle of intensive combination
treatment that includes high-dose corticosteroids results in sustained
suppression of the rate of radiologic progression in patients
with early RA, independent of subsequent antirheumatic therapy.
-----
Swed Dent J. 2002;26(4):149-58.
Long-term follow-up
of intra-articular injections into the temporomandibular joint
in patients with rheumatoid arthritis.
Vallon D, Akerman S, Nilner M, Petersson A.
Department of Stomatognathic Physiology, Faculty of Odontology,
Malmo University, Malmo, Sweden. danila.vallon@od.mah.se
A long-term (12 years) follow-up of
treatment with intra-articular injections into the temporomandibular
joint (TMJ) of steroid or non-steroid agents was performed in
21 patients with rheumatoid arthritis (RA) and symptomatic TMJs.
The aim of the study was to compare symptoms, signs and radiological
appearance of the TMJ initially and at the follow-up in this group
of patients. Eleven patients were assigned to a steroid group
and 10 patients to a non-steroid group. Initial and follow-up
clinical and radiological examination procedures were the same.
The radiological evaluation was based on a grading system using
standard reference films. At follow-up, 14 patients reported no
pain from the TMJ and positive changes in most clinical variables
were found in both groups. Radiographic follow-up examination
was performed on 12 patients. Initially, all but 4 of the 24 joints
had structural bone changes. At follow-up, 2 joints had lower,
11 joints had unchanged and 11 joints had higher radiological
grades. Two out of 5 and 3 out of 10 joints in the steroid and
non-steroid group, respectively, showed progression of structural
bone changes. Among 9 untreated joints, 6 had higher radiological
grades and 3 were unchanged. In the 11 TMJs with higher radiological
grades at follow-up, there was in most cases moderate progression
of erosive changes. The results suggest that the long-term development
of symptoms and signs from the TMJ in patients previously treated
was good and the long-term progression of joint destruction was
low for both steroid and non-steroid agents in this patient group
with RA.
©Copyright 1992-date by The Center
for Current Research. The Arthritis File is a proprietary compilation
of the Center for Current Research. The information in the File
is solely for your use, and the use of your family, friends, and
doctors. The information is the property of the individual researchers
and institutions that produced it. It is an infringement of copyright
law to attempt to "resell" the information as it is
presented here.
|
