Rheumatoid Arthritis: Wells G

Aletaha D, Landewe R, Karonitsch T, Bathon J, Boers M, Bombardier C, Bombardieri S, Choi H, Combe B, Dougados M, Emery P, Gomez-Reino J, Keystone E, Koch G, Kvien TK, Martin-Mola E, Matucci-Cerinic M, Michaud K, O'Dell J, Paulus H, Pincus T, Richards P, Simon L, Siegel J, Smolen JS, Sokka T, Strand V, Tugwell P, van der Heijde D, van Riel P, Vlad S, van Vollenhoven R, Ward M, Weinblatt M, Wells G, White B, Wolfe F, Zhang B, Zink A, Felson D, Anonymous00358, Anonymous00359. · Medical University of Vienna, Vienna, Austria. · Arthritis Rheum. · Pubmed #18821648 No free full text.

Abstract: OBJECTIVE: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: The project followed the EULAR standardized operating procedures, which use a three-step approach: 1) expert-based definition of relevant research questions (November 2006); 2) systematic literature search (November 2006 to May 2007); and 3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). RESULTS: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature, the expert panel recommended that each trial should report the following items: 1) disease activity response and disease activity states; 2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; 3) baseline disease activity levels (in general); 4) the percentage of patients achieving a low disease activity state and remission; 5) time to onset of the primary outcome; 6) sustainability of the primary outcome; 7) fatigue. CONCLUSION: These recommendations endorsed by EULAR and ACR will help harmonize the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.

van Tuyl LH, Vlad SC, Felson DT, Wells G, Boers M. · VU University Medical Center, Amsterdam, The Netherlands. · Arthritis Rheum. · Pubmed #19405006 No free full text.

Abstract: OBJECTIVE: Due to advances in rheumatoid arthritis (RA) therapies over the last few years, an increasing proportion of patients are able to achieve a state of remission. However, the definition of remission is unclear. Currently, randomized controlled trials around the world use different remission definitions and consequently measure different aspects of a patient's disease state. The need for a uniform definition of remission is vital for research findings to be correctly interpreted. METHODS: The American College of Rheumatology (ACR) constituted a committee that included international clinical researchers, trialists, and clinical epidemiologists in order to redefine remission in RA. This group was asked to study current definitions of remission, explore the theoretical underpinning of the concept of remission, and develop a research agenda that would inform future work in the development of an ACR definition of remission. RESULTS: In its first meeting, the committee preferred to develop a strict definition, implying no or very low disease activity. Such a definition would need to be validated against long-term outcome, e.g., physical function and damage. CONCLUSION: The committee decided to consider both a definition for trials and a modified version for clinical practice. Since the first meeting, the ACR and the European League Against Rheumatism (EULAR) have decided to sponsor this initiative as an official ACR/EULAR collaboration.

Towheed TE, Hochberg MC, Shea BJ, Wells G. · Queen's University, Medicine and of Community Health and Epidemiology, Etherington Hall-Room 2066, Kingston, Ontario, Canada, K7L 3N6. · Cochrane Database Syst Rev. · Pubmed #17636642 No free full text.

Abstract: BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used as a pharmacologic treatment to relieve pain for patients with OA of the hip. However, these agents are associated with significant toxicity, particularly in the elderly population (age > 65 years). OBJECTIVES: To review all randomized trials of analgesics and anti-inflammatory therapy in osteoarthritis (OA) of the hip. To determine which non-steroidal, anti-inflammatory drug (NSAID) is the most effective, and which NSAID is the most toxic. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register and MEDLINE up to August 1994. Reference lists of all trials were also manually searched. SELECTION CRITERIA: All randomized controlled trials comparing non-steroidal anti-inflammatory drugs (NSAIDs) and/or analgesics in patients with Osteoarthritis. The trials selected for inclusion were identified by one reviewer (TT) and rechecked by a second (MH). DATA COLLECTION AND ANALYSIS: Qualitative assessments were performed using a quality scoring system designed for NSAID trials in rheumatoid arthritis. Both the design and analysis aspects of the trials were evaluated, each aspect being rated on a scale of 0 to 8. A quantitative method, which calculates the ratio of improvement produced by one NSAID to that produced by another, was used to rate the relative efficacy of different NSAIDs with respect to pain relief. Toxicity comparisons were made according to the reviewer findings. All quality assessments were carried out independently by two reviewers (TT, BS). All data abstraction was carried out by one reviewer (TT) and rechecked by two other reviewers (BS, GW). A consensus was reached on discrepancies. MAIN RESULTS: Forty-three trials were identified, and of these, 39 evaluated NSAIDs, while four evaluated only analgesics. The median design and analysis scores were two and four respectively. Six NSAIDs were included in at least five trials. Of these, indomethacin was rated more effective in five of its seven comparisons, but more toxic in seven of 12 comparisons. Only five of the 29 (17%) NSAID comparisons found statistically significant differences in efficacy. Of the 43 RCTs identified only 17 had statistical data available for future pooling for this meta-analysis. In the case where data was missing, authors of the trials will be contacted for inclusion of data in future reviews. AUTHORS' CONCLUSIONS: NSAID trials in patients with OA of the hip appear to be weakened by the lack of standardization of case definition of OA, and also by the lack of standardization of outcome assessments. No clear recommendations for the choice of specific NSAID therapy in hip OA can be offered at this time based on this analysis.

Wells G, Boers M, Tugwell P, Anonymous00204. · Department of Epidemiology and Community Medicine, University of Ottawa,Ottawa, Ontario, Canada. · Clin Exp Rheumatol. · Pubmed #17083764 No free full text.

Abstract: With recent advances in therapy, the proportion of patients achieving a satisfactory state of minimal disease activity (MDA) is becoming a more important measure with which to compare different treatment strategies. MDA is between high disease activity and remission and anyone in remission will also be in MDA. This paper summarizes the process of coming to a definition of minimal disease activity in rheumatoid arthritis. Two equivalent preliminary definitions of minimal disease activity for use as secondary outcome measures in clinical trials in RA are proposed: a core-set definition based on the WHO/ILAR core set and a DAS-based definition based on the DAS28.

Casimiro L, Barnsley L, Brosseau L, Milne S, Robinson VA, Tugwell P, Wells G. · University of Ottawa, School of Rehabilitation Sciences, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5. · Cochrane Database Syst Rev. · Pubmed #16235342 No free full text.

Abstract: BACKGROUND: Acupuncture has been used by rehabilitation specialists as an adjunct therapy for the symptomatic treatment of rheumatoid arthritis (RA). Acupuncture is a traditional Chinese medicine where thin needles are inserted in specific documented points believed to represent concentration of body energies. In some cases a small electrical impulse is added to the needles. Once the needles are inserted in some of the appropriate points, endorphins, morphine-like substances, have been shown to be released in the patient's system, thus inducing local or generalised analgesia (pain relief). This review is an update of the original review published in July 2002. OBJECTIVES: To evaluate the effects of acupuncture or electroacupuncture on the objective and subjective measures of disease activity in patients with RA. SEARCH STRATEGY: A comprehensive search of MEDLINE, EMBASE, PEDro, Current Contents , Sports Discus and CINAHL, initially done in September 2001, was updated in May 2005.The Cochrane Field of Rehabilitation and Related Therapies and the Cochrane Musculoskeletal Review Group were also contacted for a search of their specialized registries. Handsearching was conducted on all retrieved papers and content experts were contacted to identify additional studies. SELECTION CRITERIA: Comparative controlled studies, such as randomized controlled trials and controlled clinical trials in patients with RA were eligible. Trials published in languages other than French and English were not analyzed. Abstracts were excluded unless further data could be obtained from the authors. DATA COLLECTION AND ANALYSIS: Two independent reviewers identified potential articles from the literature search and extracted data using pre-defined extraction forms. Consensus was reached on all the extracted data. Quality was assessed by two reviewers using a five point validated tool that measured the quality of randomization, double-blinding and description of withdrawals. MAIN RESULTS: After the updated searches were conducted, five further potential articles were identified; however, these did not meet the inclusion criteria. Two studies involving a total of 84 people were included. One study used acupuncture while the other used electroacupuncture. In the acupuncture study, no statistically significant difference was found between groups for erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analogue scale for patient's global assessment (VAS G), number of swollen joints and tender joints, general health questionnaire (GHQ), modified disease activity scale (DAS) or for the decrease in analgesic intake. Although not statistically significant, pain in the treatment group improved by 4 points on a 0-100mm visual analogue scale versus no improvement in the placebo group. In the second study, using electroacupuncture, a significant decrease in knee pain was reported in the experimental group, 24 hours post treatment, when compared to the placebo group (WMD: -2.0 with 95% CI -3.6,-4.0). A significant decrease was found also at four months post-treatment (WMD -0.2, 95% CI: -0.36, -0.04) AUTHORS' CONCLUSIONS: Although the results of the study on electroacupuncture show that electroacupuncture may be beneficial to reduce symptomatic knee pain in patients with RA 24 hours and 4 months post treatment, the reviewers concluded that the poor quality of the trial, including the small sample size preclude its recommendation. The reviewers further conclude that acupuncture has no effect on ESR, CRP, pain, patient's global assessment, number of swollen joints, number of tender joints, general health, disease activity and reduction of analgesics. These conclusions are limited by methodological considerations such as the type of acupuncture (acupuncture vs electroacupuncture), the site of intervention, the low number of clinical trials and the small sample size of the included studies.

Brosseau L, Robinson V, Wells G, Debie R, Gam A, Harman K, Morin M, Shea B, Tugwell P. · University of Ottawa, School of Rehabilitation Sciences, Faculty of Health Sciences, 451 Smyth Road, Ottawa, Ontario, Canada K1H-8M5. · Cochrane Database Syst Rev. · Pubmed #16235295 No free full text.

Abstract: BACKGROUND: Rheumatoid arthritis (RA) affects a large proportion of the population. Low Level Laser Therapy (LLLT) was introduced as an alternative non-invasive treatment for RA about ten years ago. LLLT is a light source that generates extremely pure light, of a single wavelength. The effect is not thermal, but rather related to photochemical reactions in the cells. The effectiveness of LLLT for rheumatoid arthritis is still controversial. This review is an update of the original review published in October 1998. OBJECTIVES: To assess the effectiveness of LLLT in the treatment of RA. SEARCH STRATEGY: We initially searched MEDLINE, EMBASE (from 1998), the registries of the Cochrane Musculoskeletal Group and the field of Rehabilitation and Related Therapies as well as the Cochrane Central Register of Controlled Trials (CENTRAL) up to June 2001. This search has now been updated to include articles published up to June 2005. SELECTION CRITERIA: Following an a priori protocol, only randomized controlled trials of LLLT for the treatment of patients with a clinical diagnosis of RA were eligible. Abstracts were excluded unless further data could be obtained from the authors. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, then extracted data and assessed quality using predetermined forms. Heterogeneity was tested using chi-squared. A fixed effects model was used throughout for continuous variables, except where heterogeneity existed, in which case, a random effects model was used. Results were analyzed as weighted mean differences (WMD) with 95% confidence intervals (CI), where the difference between the treated and control groups was weighted by the inverse of the variance. Dichotomous outcomes were analyzed with relative risks. MAIN RESULTS: A total of 222 patients were included in the five placebo-controlled trials, with 130 randomized to laser therapy. Relative to a separate control group, LLLT reduced pain by 1.10 points (95% CI: 1.82, 0.39) on visual analogue scale relative to placebo, reduced morning stiffness duration by 27.5 minutes (95%CI: 2.9 to 52 minutes) and increased tip to palm flexibility by 1.3 cm (95% CI: 0.8 to 1.7). Other outcomes such as functional assessment, range of motion and local swelling did not differ between groups. There were no significant differences between subgroups based on LLLT dosage, wavelength, site of application or treatment length. For RA, relative to a control group using the opposite hand, there was no difference observed between the control and treatment hand for morning stiffness duration, and also no significant improvement in pain relief RR 13.00 (95% CI: 0.79 to 214.06). However, only one study was included as using the contralateral limb as control. . AUTHORS' CONCLUSIONS: LLLT could be considered for short-term treatment for relief of pain and morning stiffness for RA patients, particularly since it has few side-effects. Clinicians and researchers should consistently report the characteristics of the LLLT device and the application techniques used. New trials on LLLT should make use of standardized, validated outcomes. Despite some positive findings, this meta-analysis lacked data on how LLLT effectiveness is affected by four important factors: wavelength, treatment duration of LLLT, dosage and site of application over nerves instead of joints. There is clearly a need to investigate the effects of these factors on LLLT effectiveness for RA in randomized controlled clinical trials.

Garner SE, Fidan DD, Frankish RR, Judd MG, Towheed TE, Wells G, Tugwell P. · Department of Community Health Sciences, St George's Hospital Medical School, Cranmer Terrace, Tooting, London, UK, SW17 0RE. · Cochrane Database Syst Rev. · Pubmed #15674912 No free full text.

Abstract: BACKGROUND: Editor's note: The anti-inflammatory drug rofecoxib (Vioxx) was withdrawn from the market at the end of September 2004 after it was shown that long-term use (greater than 18 months) could increase the risk of heart attack and stroke. Further information is available at www.vioxx.com.Rheumatoid arthritis (RA) is a systemic auto-immune disorder, in which the synovial lining of many joints and tendon sheaths are persistently inflamed. OBJECTIVES: To assess the efficacy and toxicity of rofecoxib for treating RA. SEARCH STRATEGY: We searched the following electronic databases up to December 2000: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment database. The bibliographies of retrieved papers were scanned for additional references. The manufacturers of rofecoxib, MSD, were also approached by the UK National Institute for Clinical Excellence to submit additional evidence to inform it's appraisal on the use of cyclo-oxygenase inhibitors for arthritis. SELECTION CRITERIA: We included randomised controlled trials of parallel group design evaluating the efficacy and/or toxicity of rofecoxib in RA, both placebo based and comparative trials were eligible. Relevant outcome criteria had to be available to evaluate efficacy and/or toxicity, such as the OMERACT outcomes. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers and the results were compared for the degree of agreement. A validated tool (Jadad 1996) was used to score the quality of the randomised controlled trials. The planned analysis was to pool, where appropriate, continuous outcome measures using mean or standardized mean differences, and dichotomous outcome measures using relative risk ratios. MAIN RESULTS: Two randomised controlled trials evaluating rofecoxib for the treatment of RA were identified and met the inclusion criteria. One compared rofecoxib to placebo and was designed to assess the safety and efficacy of several doses of rofecoxib. The second trial compared rofecoxib to naproxen and was primarily designed to assess the safety of rofecoxib so did not include all the recommended RA efficacy measures. The overall number of ACR 20 responders who had received 25mg (82/ 171 = 48%) or 50mg (86/161 = 53%) was statistically significantly more than those receiving placebo (58/168 = 35% ) (RR 1.39 CI: 1.07, 1.80 and RR 1.55 CI: 1.20, 1.99 respectively) with no statistically significant differences between the 25 and 50 mg doses. The safety profile of rofecoxib was similar to that of placebo. In the comparative trial, rofecoxib at a dosage of 50 mg/day demonstrated similar efficacy to naproxen at a dosage of 500 mg twice daily. However, the combined rate of clinically significant complicated gastro-intestinal events (GI) (perforations, ulcers, bleeds, or obstructions) was lower with rofecoxib than with naproxen (RR 0.46, 95% CI, 0.34 to 0.63) due to a reduction in the number of ulcers and bleeds. Compared to patients taking naproxen, patients taking rofecoxib had a greater risk of having any cardiovascular event (45/4047 = 1.1% vs 19/4029 =0.47%) (RR 2.36 CI 1.38 to 4.02) and had greater risk of having a non-fatal myocardial infarction (MI) (18/4047 =0 .44% and 4/4029 =0.1%) (RR 4.48, 95% CI, 1.52 to 13.23). AUTHORS' CONCLUSIONS: In patients with RA, rofecoxib demonstrates a greater degree of efficacy than placebo, while having a comparable safety profile. Rofecoxib demonstrates a similar degree of efficacy as naproxen, but with a significantly lower rate of ulceration and gastrointestinal bleeding. Rofecoxib was associated with a greater risk for MI, but the exact significance and pathophysiology of this possible relationship is unclear.Rofecoxib was voluntarily withdrawn from global markets in October 2004. It cannot therefore be prescribed and therefore there are no implications for practice concerning its use. None the less when considering which NSAID to use, it must be borne in mind that the toxicity of NSAIDs is variable amongst patients and drugs and it tends to be dose related and associated with variation in the mode of action, absorption, distribution and metabolism.There remains a number of questions over both the benefits and risks associated with Cox II selective agents and further work is ongoing. It is likely that this issue will not be resolved until research has enabled a fuller understanding of the complex mechanism by which the Cox system operates.

Han A, Robinson V, Judd M, Taixiang W, Wells G, Tugwell P. · 5-83 Pape Avenue, Toronto, Ontario, Canada, M4M 2V5. · Cochrane Database Syst Rev. · Pubmed #15266544 No free full text.

Abstract: BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic inflammatory autoimmune disease that results in the destruction of the musculoskeletal system. The major goals of treatment are to relieve pain, reduce inflammation, slow down or stop joint damage, prevent disability, and preserve or improve the person's sense of well-being and ability to function. Tai Chi, interchangeably known as Tai Chi Chuan, is an ancient Chinese health-promoting martial art form that has been recognized in China as an effective arthritis therapy for centuries. OBJECTIVES: To assess the effectiveness and safety of Tai Chi as a treatment for people with RA. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (CCTR), MEDLINE, Pedro and CINAHL databases up to September 2002, using the Cochrane Collaboration search strategy for randomised controlled trials. We also searched the Chinese Biomedical Database up to December 2003 and the Beijing Chinese Academy of Traditional Medicine up to December 2003. SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials examining the benefits and harms of exercise programs with Tai Chi instruction or incorporating principles of Tai Chi philosophy were selected. We included control groups who received no therapy, sham therapy or another type of therapy. DATA COLLECTION AND ANALYSIS: Two reviewers determined the studies to be included in this review, rated the methodological quality and extracted data using standardized forms. MAIN RESULTS: Four trials including 206 participants, were included in this review. Tai Chi-based exercise programs had no clinically important or statistically significant effect on most outcomes of disease activity, which included activities of daily living, tender and swollen joints and patient global overall rating. For range of motion, Tai Chi participants had statistically significant and clinically important improvements in ankle plantar flexion. No detrimental effects were found. One study found that compared to people who participated in traditional ROM exercise/rest programs those in a Tai Chi dance program reported a significantly higher level of participation in and enjoyment of exercise both immediately and four months after completion of the Tai Chi program. REVIEWERS' CONCLUSIONS: The results suggest Tai Chi does not exacerbate symptoms of rheumatoid arthritis. In addition, Tai Chi has statistically significant benefits on lower extremity range of motion, in particular ankle range of motion, for people with RA. The included studies did not assess the effects on patient-reported pain.

Blumenauer B, Judd M, Cranney A, Burls A, Coyle D, Hochberg M, Tugwell P, Wells G. · No affiliation provided · Cochrane Database Syst Rev. · Pubmed #14584021 No free full text.

Abstract: BACKGROUND: Etanercept is a soluble tumour necrosis factor alpha-receptor DMARD for the treatment of rheumatoid arthritis (RA). OBJECTIVES: To assess the efficacy and safety of etanercept for the treatment of RA. SEARCH STRATEGY: Five electronic databases were searched from 1966 to February 2003 with no language restriction. SELECTION CRITERIA: All randomized controlled trials (minimum 6 month duration) comparing three possible combinations 1) etanercept (10 mg or 25 mg twice weekly) with methotrexate (MTX) to MTX alone 2) etanercept to MTX, or 3) etanercept to placebo were eligible. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data and assessed the methodological quality of the trails. The American College of Rheumatology (ACR) core set of disease activity measures for RA clinical trials, radiographic, withdrawals and toxicity outcomes were analyzed. MAIN RESULTS: Three trials were included in this review. Two trials compared an experimental group who were started on etanercept compared to a control group; both groups had the same ongoing background therapy of nonsteroidals in both trials plus in one trial one group was on stable methotrexate.In these two trials the ACR 20, ACR 50 and ACR 70 response rates at 6 months were statistically significantly and clinically important with etanercept 25 mg subcutaneous injections (SC) twice weekly. Sixty-four percent of people receiving etanercept ache vied an ACR 20 response compared to 15% of controls and the number needed to treat (NNT) with etanercept is 2 people. Thirty-nine percent of those receiving etanercept achieved an ACR 50 response compared to 4% of taking control treatment and the NNT is three.Fifteen percent of people taking etanercept achieved an ACR 70 compared to 1% of controls with a NNT of 7 people.In the third trial of starting etanercept compared to starting methotrexate the number of participants who achieved an ACR 20, 50 or response at 6 and 12 months were not statistically significant for either etanercept dose.Etanercept treatment showed a statistically significantly and clinically important affect on joint damage as measured by the Sharp erosion score. Among participants who received etanercept 72% had no increase in their erosion score compared to 60% of participants in the methotrexate group. Withdrawal and toxicity results were acceptable. REVIEWER'S CONCLUSIONS: Etanercept 25 mg SC twice weekly was more efficacious than control treatment for ACR 20, 50 and 70 at 6 months, and over 12 months it slowed joint damage.

Brosseau L, Judd MG, Marchand S, Robinson VA, Tugwell P, Wells G, Yonge K. · School of Rehabilitation Sciences, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada, K1H 8M5. · Cochrane Database Syst Rev. · Pubmed #12918009 No free full text.

Abstract: BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory, system disease. It commonly affects the small peripheral joints (such as fingers and wrist). The main goals of intervention for RA are preventing joint deformity, preserving joint function, and reducing inflammation and pain. Transelectrical nerve stimulation (TENS) is a form of electrotherapy and is thought to produce analgesia according to the gate control theory. OBJECTIVES: To determine the efficacy and safety of TENS in the treatment of RA of the hand. The primary outcomes of interest were relief of grip pain and resting pain intensity, relief of joint tenderness, number of tender joints and patient assessment of disease. The secondary objective was to determine the most effective mode of TENS application in pain control. SEARCH STRATEGY: We searched for relevant studies, in English, in the Cochrane field of physical and related therapies, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, HEALTHSTAR, Sports Discus, CINAHL, Current Contents, and the PEDro database, up to October 2002. SELECTION CRITERIA: Two independent reviewers selected the trials that met predetermined inclusion criteria. DATA COLLECTION AND ANALYSIS: Study results were extracted by two independent reviewers. Continuous outcomes were analyzed by weighted mean difference (WMD) using a fixed effects model. MAIN RESULTS: Three RCTs, involving 78 people, were included in this review. AL-TENS and C-TENS were compared to placebo and to each other. Administration of 15 minutes of AL-TENS a week, for 3 weeks, resulted in a significant decrease in rest pain (67% relative benefit, 45 points absolute benefit on 100 mm VAS scale) but not in grip pain compared to placebo. AL-TENS did result in a clinical beneficial improvement in muscle power scores with a relative difference of 55%, and an absolute benefit of 0.98, compared to placebo. No significant difference was found between one 20-minute treatment duration of C-TENS versus AL-TENS, or C-TENS versus placebo on decrease in mean scores for rest pain or grip pain, or on the number of tender joints. Results showed a statistically significant reduction in joint tenderness, but no clinical benefit from C-TENS over placebo in relief of joint tenderness. No statistically significant difference was shown between 15 days of treatment with C-TENS or AL-TENS in relief of joint pain, although there was a clinically important benefit of C-TENS over AL-TENS on patient assessment of change in disease (risk difference 21%, NNT 5). REVIEWER'S CONCLUSIONS: There are conflicting effects of TENS on pain outcomes in patients with RA. AL-TENS is beneficial for reducing pain intensity and improving muscle power scores over placebo while, conversely, C-TENS resulted in no clinical benefit on pain intensity compared with placebo. However C-TENS resulted in a clinical benefit on patient assessment of change in disease over AL-TENS. More well designed studies with a standardized protocol and adequate number of subjects are needed to fully conclude the effect of C-TENS and AL-TENS in the treatment of RA of the hand.

Milne S, Brosseau L, Robinson V, Noel MJ, Davis J, Drouin H, Wells G, Tugwell P. · School of Rehabilitation Sciences, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada, K1H 8M5. · Cochrane Database Syst Rev. · Pubmed #12804511 No free full text.

Abstract: BACKGROUND: Knee arthroplasty (KA) is a common intervention that can enhance the quality of life for patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Post-surgery rehabilitation protocols often include continuous passive motion (CPM). However, CPM protocols vary considerably amongst institutions. OBJECTIVES: The purpose of the current meta-analysis is to evaluate the effectiveness of continuous passive motion following total knee arthroplasty. SEARCH STRATEGY: An electronic search of MEDLINE (1966 to 2002), EMBASE (1988 to 2002), CINAHL (1982 to 2002), HEALTH STAR (1991 to 1994) and CURRENT CONTENTS (1997 to 2002) was conducted to identify randomized controlled trials. SELECTION CRITERIA: Following an a priori protocol, only randomized controlled trials of CPM for the treatment of participants post KA were eligible. Subjects were 18 years of age or older and had a pre-surgery diagnosis of degenerative joint disease. Both the experimental and control groups received physiotherapy. In addition to the physiotherapy intervention, the experimental group received CPM. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion. Data were then extracted and the quality of the trial assessed using predetermined forms. Outcome measures of interest were: active and passive knee range of motion (ROM) length of hospital stay, pain, swelling and quadriceps strength. A fixed effects model was used throughout for continuous variables, except where heterogeneity existed; in which case, a random effects model was used. Results were analyzed as weighted mean differences (WMD) with 95% confidence intervals (CI). Standardized mean differences (SMD) were used when different scales were used to measure the same concept (e.g. pain). Dichotomous outcomes were presented as a relative risk. MAIN RESULTS: Fourteen trials were retained for analysis. Results favouring CPM were found for the main comparison of CPM combined with physiotherapy (PT) versus PT alone at end of treatment. For the primary outcomes of interest, CPM combined with PT was found to statistically significantly increase active knee flexion (WMD 4.30 degrees, 95% CI: 1.96, 6.63) and decrease length of stay (WMD -0.69 days, 95% CI: -1.35, -0.03). CPM was also found to decrease the need for post-operative manipulation (RR 0.12, 95% CI: 0.03, 0.53). CPM did not significantly improve passive knee flexion and passive or active knee extension. REVIEWER'S CONCLUSIONS: CPM combined with PT, may offer beneficial results compared to PT alone in the short term rehabilitation following total knee arthroplasty.

Wells G, Anderson J, Boers M, Felson D, Heiberg T, Hewlett S, Johnson K, Kirwan J, Lassere M, Robinson V, Shea B, Simon L, Strand V, van Riel P, Tugwell P. · Department of Clinical Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada. · J Rheumatol. · Pubmed #12734920 No free full text.

Abstract: The OMERACT 6 Minimal Clinically Important Difference/Low Disease Activity Workshop was organized with the aim of meeting the many challenges that exist in determining a low disease activity in rheumatoid arthritis (RA). This article presents an overview of that workshop, including results of the voting, a summary of associated discussions, recommendations, and a proposed research agenda.

Wells G, Boers M, Shea B, Anderson J, Felson D, Johnson K, Kirwan J, Lassere M, Robinson V, Simon L, Strand V, van Riel P, Tugwell P. · Department of Clinical Epidemiology and Community Medicine, University of Ottawa, Ottawa, Canada. · J Rheumatol. · Pubmed #12734918 No free full text.

Abstract: The MCID (minimal clinically important difference) module of OMERACT 5 developed a research agenda that led to the conclusion that a state of low disease activity for rheumatoid arthritis (RA) would need to be defined. To develop such a definition the various concepts and terminologies, the process for developing an operational definition, and the availability and design of longitudinal datasets for validation needed to be considered. This article describes the process of the MCID/Low Disease Activity State Workshop at OMERACT 6 to develop such a definition.

Egan M, Brosseau L, Farmer M, Ouimet MA, Rees S, Wells G, Tugwell P. · Rehabilitation Sciences, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada, K1H 8M5. · Cochrane Database Syst Rev. · Pubmed #12535502 No free full text.

Abstract: BACKGROUND: Splints/orthoses are often recommended to patients with rheumatoid arthritis (RA) to decrease pain, decrease swelling and/or prevent deformity. These orthoses include resting hand splints, wrist supports, finger splints and special shoes and shoe inserts. OBJECTIVES: To assess the effectiveness of splints/orthoses in relieving pain, decreasing swelling and/or preventing deformity and determine the impact of splints/orthoses on strength, mobility and function in people with RA. SEARCH STRATEGY: We searched MEDLINE, EMBASE, the PEDro data base and Current Contents up to January 2002, and the Cochrane Controlled Trials Register to Issue 4, 2001 using the search strategy developed by the Cochrane Collaboration. Unpublished studies were sought by hand searching conference proceeding and contacting key experts. SELECTION CRITERIA: All randomized control trials (RCTs) and controlled clinical trials (CCTs), case-control and cohort studies comparing the use of specific orthoses against placebo, another active intervention (including another type of orthoses) or regular treatment were selected, according to an a priori protocol. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected the studies and abstracted data. The methodological quality of the RCTs and CCTs was assessed using a validated scale. MAIN RESULTS: Twelve papers reporting on 10 studies met the inclusion criteria. These studies dealt with the following: working wrist splints (5), resting hand and wrist splints (2), special shoes and insoles (3). There is evidence that wearing working wrist splints statistically significantly decreases grip strength and does not affect pain, morning stiffness, pinch grip, quality of life after up to 6 months of regular wear. We found no evidence that resting wrist and hand splints change pain, grip strength, Ritchie Index or number of swollen joints. However, patients who wore these splints for 2 months reported that they preferred use to non-use and padded resting splints to unpadded ones. The one study of special shoes provided evidence of significant benefits of wearing extra-depth shoes for 2 months including less pain on walking and stair climbing and more minutes pain free walking time. Extra-depth shoes with semi-rigid insoles provided better pain relief than extra-depth shoes alone when worn over 12 weeks. Posted insoles prevented progression of hallux valgus angle but did not affect pain or function. REVIEWER'S CONCLUSIONS: There is insufficient evidence to make firm conclusions about the effectiveness of working wrist splints in decreasing pain or increasing function for people with RA. Potential adverse effects such as decreased range of motion do not seem to be an issue, although some of these splints decrease grip strength and dexterity. Similarly, preliminary evidence suggests that resting hand and wrist splints do not seem to affect range of motion or pain, although patients preferred wearing a resting splint to not wearing one. There is evidence that extra-depth shoes and molded insoles decreases pain on weight-bearing activities such as standing, walking and stair-climbing. Posted insoles may be effective in preventing progression of hallux abductus angle but do not appear to have an impact on pain.

Osiri M, Shea B, Robinson V, Suarez-Almazor M, Strand V, Tugwell P, Wells G. · Medicine, Chulalongkorn University Hospital, Division of Rheumatology, Department of Medicine, Chulalongkorn University Hospital, Rama IV Road, Pathumwan, Bangkok, Thailand, 10330. · Cochrane Database Syst Rev. · Pubmed #12535423 No free full text.

Abstract: BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease. Leflunomide, as an inhibitor of pyrimidine synthesis, has a different mechanism of action than other existing disease modifying anti-rheumatic drugs (DMARD). OBJECTIVES: To determine the efficacy and toxicity of leflunomide compared to placebo or other DMARDs in the treatment of RA. SEARCH STRATEGY: We conducted a search in MEDLINE, EMBASE, Current Contents and the Cochrane Controlled Trial Register for trials up to December 2001. We also hand-searched reference lists and consulted content experts. SELECTION CRITERIA: Two independent reviewers selected the trials that met predetermined inclusion criteria. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data and assessed methodologic quality using standardized forms. MAIN RESULTS: Six trials were included in this review. Using the ACR20 improvement criteria, there was an absolute difference in improvement of 28% (95% confidence interval: 21 - 35%) favouring leflunomide (232 out of 413 leflunomide treated patients compared to 89 out of 311 placebo patients met the criteria). There was no difference in ACR20 response rate between the patients treated with leflunomide and SSZ or MTX at 6 and 12 months. Other clinical outcomes were improved significantly in the leflunomide group compared to placebo but not different from SSZ or MTX. Withdrawals due to adverse events with leflunomide were 10% greater than placebo (70 out of 416 compared to 18 out of 311 respectively). Important adverse events included gastrointestinal symptoms, elevated liver function tests, alopecia, and infections. Overall adverse events and withdrawals in the leflunomide group were not significantly different from SSZ or MTX. REVIEWER'S CONCLUSIONS: Leflunomide appears to improve all clinical outcomes and delay radiologic progression at both 6 and 12 months of treatment compared to placebo. Its efficacy and adverse events at 2 years of treatment are comparable to SSZ and MTX. Long-term efficacy and toxicity remains to be established.

Garner S, Fidan D, Frankish R, Judd M, Shea B, Towheed T, Wells G, Tugwell P. · Department of Public Health, St. George's Hospital Medical School, Cranmer Terrace, London, UK, SW17 0RE. · Cochrane Database Syst Rev. · Pubmed #12519610 No free full text.

Abstract: BACKGROUND: Rheumatoid arthritis (RA) is a systemic auto-immune disorder, involving persistent joint inflammation. NSAIDs are used to control the symptoms of RA, but are associated with significant gastro-intestinal toxicity, including a risk of potentially life threatening gastroduodenal perforations, ulcers and bleeds. The NSAIDs known as the selective Cox II inhibitors, of which celecoxib is a member, were developed in order to reduce the GI toxicity, but are more expensive. OBJECTIVES: To establish the efficacy and safety of celecoxib in the management of RA by systematic review of available evidence. SEARCH STRATEGY: We searched the following databases up to August 2002: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment Database. The bibliographies of retrieved papers and content experts were consulted for additional references. SELECTION CRITERIA: All eligible randomised controlled trials (RCTs) were included. No unpublished RCTs were included in this edition of the review. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers. Data was analysed using a fixed effects model. A validated checklist was used to score the quality of the RCTs. The planned analysis was to pool, where appropriate continuous outcomes using mean differences and dichotomous outcomes using relative risk ratios. This was not however possible due to the lack of data. MAIN RESULTS: Five RCTs were included (4465 participants); three of the studies also enrolled individuals with OA. The comparators were placebo, naproxen, diclofenac and ibuprofen. The evidence reviewed suggests that celecoxib controls the symptoms of RA to a similar degree to that of the active comparators examined (naproxen, diclofenac and ibuprofen). When compared to placebo, the percentage of patients showing improvement according to ACR 20 criteria at week 4 were 42/82 (51%) in the twice daily celecoxib 200mg group and 43/82 (52%) in the twice daily celecoxib 400mg group; these were significantly different from the placebo group in which 25/85 (29%) improved. The six month data reviewed support a reduced rate of UGI complications with celecoxib but there is also evidence to suggest that these benefits may not be evident in the long-term and that celecoxib offers no additional benefit in patients who are also receiving cardio-prophylactic low dose aspirin. REVIEWER'S CONCLUSIONS: For an individual with RA the potential benefits of celecoxib need to be balanced against the uncertainty that the short-term reduced incidence of upper GI complications are maintained in the long-term and its increased cost in comparison to traditional NSAIDs.

Casimiro L, Brosseau L, Milne S, Robinson V, Wells G, Tugwell P. · School of Rehabilitation Sciences, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada, K1H 8M5. · Cochrane Database Syst Rev. · Pubmed #12137715 No free full text.

Abstract: BACKGROUND: Acupuncture has been used by rehabilitation specialists as an adjunct therapy for the symptomatic treatment of rheumatoid arthritis (RA). Acupuncture is a traditional Chinese medicine where thin needles are inserted in specific documented points believed to represent concentration of body energies. In some cases a small electrical impulse is added to the needles. Once the needles are inserted in some of the appropriate points, endorphins, morphine-like substances, have been shown to be released in the patient's system, thus inducing local or generalised analgesia. OBJECTIVES: To evaluate the effects of acupuncture or electroacupuncture on the objective and subjective measures of disease activity in patients with RA. SEARCH STRATEGY: A comprehensive search was done up to September 2001 with MEDLINE, EMBASE, PEDro, Current Contents, Sports Discus and CINAHL. The Cochrane Field of Rehabilitation and Related Therapies and the Cochrane Musculoskeletal Review Group were also contacted for a search of their specialized registers. Handsearching was conducted on all retrieved papers and content experts were contacted to identify additional studies. SELECTION CRITERIA: Comparative controlled studies, such as randomized controlled trials and control clinical trials in patients with RA were eligible. No language restrictions were applied. Abstracts were accepted. DATA COLLECTION AND ANALYSIS: Two independent reviewers identified potential articles from the literature search. These reviewers extracted data using pre-defined extraction forms. Consensus was reached on all the extracted data. Quality was assessed by two reviewers using a five (5) point validated tool that measured the quality of randomization, double-blinding and description of withdrawals. MAIN RESULTS: Two studies (n=84) met the inclusion criteria. One used acupuncture (~~David 1999~~) while the other used electroacupuncture (~~Man 1974~~). In the first study using acupuncture, no significant difference was found between groups for to erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), the visual analogue scale for pain (VAS P), the visual analogue scale for patient's global assessment (VAS G), the number of swollen joints, the number of tender joints, to the general health questionnaire (GHQ), the score on the modified disease activity scale (DAS) or in the decrease in analgesic intake. In the second study, using electroacupuncture, a significant decrease in knee pain was reported in the experimental group, 24 hours post treatment, when compared to the placebo group (weighted mean difference of -2.0 with 95% CI -3.6,-4.0). REVIEWER'S CONCLUSIONS: Although the results of the ~~Man 1974~~ study show that electroacupuncture may be beneficial to reduce symptomatic knee pain in patients with RA 24 hours post treatment, the reviewers concluded that the poor quality of the trial, including the small sample size proclude its recommendation. The reviewers further conclude that acupuncture has no effect on ESR, CRP, pain, patient's global assessment, number of swollen joints, number of tender joints, general health, disease activity and reduction of analgesics. These conclusions are limited by methodological considerations such as the type of acupuncture (acupuncture vs electroacupuncture), the site of intervention, the low number of clinical trials and the small sample size of the included studies.

Blumenauer B, Judd M, Wells G, Burls A, Cranney A, Hochberg M, Tugwell P. · Department of Rheumatology, Ottawa Hospital, University of Ottawa. · Cochrane Database Syst Rev. · Pubmed #12137712 No free full text.

Abstract: BACKGROUND: Infliximab is a human murine chimeric anti-tumour necrosis factor alpha monoclonal antibody recently approved for the treatment of refractory RA. OBJECTIVES: To assess the efficacy and safety of infliximab for the treatment of rheumatoid arthritis. SEARCH STRATEGY: Electronic databases including Biological Abstracts, CINAHL, Current Contents, Dissertation Abstracts, EBM Reviews, HealthSTAR and MEDLINE were searched from 1966 to March 2002. Rheumatoid arthritis was searched as an exploded MESH heading. Infliximab was searched as a text word as it is not currently indexed. The search was not limited by language, year of publication or type of publication. The specific search strategy is shown below. SELECTION CRITERIA: All randomized controlled trials comparing infliximab 1, 3, 5 or 10 mg/kg with methotrexate(MTX) to MTX alone, or without MTX to placebo, with a minimum duration of 6 months and at least 2 infusions were eligible. DATA COLLECTION AND ANALYSIS: Data was extracted by 2 independent reviewers and the methodological quality of the trials was assessed using a validated assessment tool scale. Outcome variables included the ACR core set of disease activity measures for RA clinical trials and radiographic outcome data. Withdrawals and toxicity were also included. End of trial results were pooled. Continuous data were pooled using weighted mean differences and dichotomous data using relative risks. MAIN RESULTS: Two trials with a total of 529 patients met the inclusion criteria. Patients fulfilling the American Rheumatism Association 1987 RA diagnostic criteria were randomized to receive either infliximab 1mg/kg (with and without MTX), 3mg/kg(with and without MTX), 10mg/kg of infliximab (with and without MTX) or placebo infusion plus MTX. Infusions were given every 4 or 8 weeks. After 6 months ACR 20, ACR 50 and ACR 70 response rates were significantly improved in all infliximab doses compared to control. The number needed to treat with infliximab to achieve an ACR 20, 50 or 70 response in patients with refractory RA under specialist care ranged from 2.9 to 3.3 for ACR 20, 3.6 to 4.8 for ACR 50 and 5.9 to 12.5 for ACR 70 depending on the dose (3mg/kg or 10mg/kg given either every 4 or 8 weeks). Total withdrawals and withdrawals due to lack of efficacy were lower for all doses of infliximab versus controls. Withdrawals for adverse events and withdrawals for other reasons were not statistically significantly different for those receiving infliximab from control. REVIEWER'S CONCLUSIONS: Treatment with infliximab for 6 and 12 months significantly reduces RA disease activity and appeared to have an acceptable safety profile in these trials. Total radiographic scores improved, fewer patients showed radiographic progression, and more patients showed radiographic improvement with infliximab treatment at 12 months compared to controls. However, only 2 trials met the inclusion criteria, and these results are largely driven by the largest trial. The available efficacy and toxicity data is relatively short-term (6-12 months). In order to detect rare events that may be associated with infliximab, larger and longer term studies are required.

Garner S, Fidan D, Frankish R, Judd M, Towheed T, Wells G, Tugwell P. · National Institute for Clinical Excellence, 11 Strand, London, UK, WC1N 5HR. · Cochrane Database Syst Rev. · Pubmed #12137705 No free full text.

Abstract: BACKGROUND: Rheumatoid arthritis (RA) is a systemic auto-immune disorder, in which the synovial lining of many joints and tendon sheaths are persistently inflamed. OBJECTIVES: To assess the efficacy and toxicity of rofecoxib for treating RA. SEARCH STRATEGY: We searched the following electronic databases up to December 2000: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment database. The bibliographies of retrieved papers were scanned for additional references. The manufacturers of rofecoxib, MSD, were also approached by the UK National Institute for Clinical Excellence to submit additional evidence to inform it's appraisal on the use of cyclo-oxygenase inhibitors for arthritis. SELECTION CRITERIA: We included randomised controlled trials of parallel group design evaluating the efficacy and/or toxicity of rofecoxib in RA, both placebo based and comparative trials were eligible. Relevant outcome criteria had to be available to evaluate efficacy and/or toxicity, such as the OMERACT outcomes. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers and the results were compared for the degree of agreement. A validated tool (Jadad 1996) was used to score the quality of the randomised controlled trials. The planned analysis was to pool, where appropriate, continuous outcome measures using mean or standardized mean differences, and dichotomous outcome measures using relative risk ratios. MAIN RESULTS: Two randomised controlled trials evaluating rofecoxib for the treatment of RA were identified and met the inclusion criteria. One compared rofecoxib to placebo and was designed to assess the safety and efficacy of several doses of rofecoxib. The second trial compared rofecoxib to naproxen and was primarily designed to assess the safety of rofecoxib so did not include all the recommended RA efficacy measures. The overall number of ACR 20 responders who had received 25mg (82/ 171 = 48%) or 50mg (86/161 = 53%) was statistically significantly more than those receiving placebo (58/168 = 35% ) (RR 1.39 CI: 1.07, 1.80 and RR 1.55 CI: 1.20, 1.99 respectively) with no statistically significant differences between the 25 and 50 mg doses. The safety profile of rofecoxib was similar to that of placebo. In the comparative trial, rofecoxib at a dosage of 50 mg/day demonstrated similar efficacy to naproxen at a dosage of 500 mg twice daily. However, the combined rate of clinically significant complicated gastro-intestinal events (GI) (perforations, ulcers, bleeds, or obstructions) was lower with rofecoxib than with naproxen (RR 0.46, 95% CI, 0.34 to 0.63) due to a reduction in the number of ulcers and bleeds. Compared to patients taking naproxen, patients taking rofecoxib had a greater risk of having any cardiovascular event (45/4047 = 1.1% vs 19/4029 =0.47%) (RR 2.36 CI 1.38 to 4.02) and had greater risk of having a non-fatal myocardial infarction (MI) (18/4047 =0.44% and 4/4029 =0.1%) (RR 4.48, 95% CI, 1.52 to 13.23). REVIEWER'S CONCLUSIONS: In patients with RA, rofecoxib demonstrates a greater degree of efficacy than placebo, while having a comparable safety profile. Rofecoxib demonstrates a similar degree of efficacy as naproxen, but with a significantly lower rate of ulceration and gastrointestinal bleeding. Rofecoxib was associated with a greater risk for MI, but the exact significance and pathophysiology of this possible relationship is unclear.

Garner S, Fidan D, Frankish R, Judd M, Towheed T, Wells G, Tugwell P. · National Institute for Clinical Excellence, 11 Strand, London, UK, WC1N 5HR. · Cochrane Database Syst Rev. · Pubmed #12076502 No free full text.

Abstract: BACKGROUND: Rheumatoid arthritis (RA) is a systemic auto-immune disorder, in which the synovial lining of many joints and tendon sheaths are persistently inflamed. OBJECTIVES: To assess the efficacy and toxicity of rofecoxib for treating RA. SEARCH STRATEGY: We searched the following databases up to December 2000: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment database. The bibliographies of retrieved papers were scanned for additional references. The manufacturers of rofecoxib, MSD, were also approached by the UK National Institue for Clincal Excellence to submit additional evidence to inform it's appraisal on the use of cyclo-oxygenase inibitors for arthritis. SELECTION CRITERIA: Relevant studies were randomised controlled trials of parallel group design evaluating the efficacy and/or toxicity of rofecoxib in RA, both placebo based and comparative trials were eligible. Relevant outcome criteria had to be available to evaluate efficacy and/or toxicity, such as the OMERACT outcomes. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers and the results were compared for the degree of agreement. A validated tool (Jadad 1995) was used to score the quality of the randomised controlled trials. The planned analysis was to pool, where appropriate, continuous outcome measures using mean or standardized mean differences, and dichotomous outcome measures using relative risk ratios. MAIN RESULTS: Two randomised controlled trials evaluating the efficacy and toxicity of rofecoxib in RA were identified and met the criteria. One compared rofecoxib to placebo and the other compared rofecoxib to naproxen. The overall number of ACR 20 responders who had received 25mg (82/ 171 = 48%) or 50mg (86/161 = 53%) was statistically significantly more than those receiving placebo (58/168 = 35% ) (RR 1.39 CI: 1.07, 1.80 and RR 1.55 CI: 1.20, 1.99 respectively) with no statistically significant differences between the 25 and 50 mg doses. The safety profile of rofecoxib was similar to that of placebo. In the comparative trial, rofecoxib at a dosage of 50 mg/day demonstrated similar efficacy to naproxen at a dosage of 500 mg twice daily. However, the combined rate of clinically significant complicated gastro-intestinal events (GI) (perforations, ulcers, bleeds, or obstructions) was lower with rofecoxib than with naproxen (RR 0.46, 95% CI, 0.34 to 0.63) due to a reduction in the number of ulcers and bleeds. Patients taking rofecoxib had a greater risk of having a myocardial infarction (MI) than patients taking naproxen (RR 4.03, 95% CI, 2.86 to 5.68). REVIEWER'S CONCLUSIONS: In patients with RA, rofecoxib demonstrates a greater degree of efficacy than placebo, while having a comparable safety profile. Rofecoxib demonstrates a similar degree of efficacy as naproxen, but with a significantly lower rate of ulceration and gastrointestinal bleeding. Rofecoxib was associated with a greater risk for MI, but the exact significance and pathophysiology of this possible relationship is unclear.

Robinson V, Brosseau L, Casimiro L, Judd M, Shea B, Wells G, Tugwell P. · Institute of Population Health, University of Ottawa, 1 Stewart Street, Ottawa, Ontario, Canada, K1N-6N5. · Cochrane Database Syst Rev. · Pubmed #12076454 No free full text.

Abstract: BACKGROUND: Thermotherapy is often used as adjunct in the treatment of rheumatoid arthritis (RA) by rehabilitation specialists. OBJECTIVES: To evaluate the effectiveness of different thermotherapy applications on objective and subjective measures of disease activity in patients with RA. SEARCH STRATEGY: We searched Medline, EMBASE, Pedro, Current Contents, Sports Discus and CINAHL up to and including September 2001. The Cochrane Field of Rehabilitation and related therapies and the Cochrane Musculoskeletal Review Group were also contacted for a search of their specialized registers. Hand searching was conducted on all retrieved articles for additional articles. SELECTION CRITERIA: Comparative controlled studies, such as randomized controlled trials, controlled clinical trials, cohort studies or case/control studies, of thermotherapy compared to control or active interventions in patients with RA were eligible. No language restrictions were applied. Abstracts were accepted. DATA COLLECTION AND ANALYSIS: Two independent reviewers identified potential articles from the literature search (VR, LB). These reviewers extracted data using pre-defined extraction forms. Consensus was reached on all data extraction. Quality was assessed by two reviewers using a 5 point scale that measured the quality of randomization, double-blinding and description of withdrawals. MAIN RESULTS: Seven studies (n=328 subjects) met the inclusion criteria. The results of this systematic review of thermotherapy for RA found that there was no significant effect of hot and ice packs applications (Ivey 1994), cryotherapy (Rembe 1970) and faradic baths (Hawkes 1986) on objective measures of disease activity including joint swelling, pain, medication intake, range of motion (ROM), grip strength, hand function compared to a control (no treatment) or active therapy. There is no significant difference between wax and therapeutic ultrasound as well as between wax and faradic bath combined to ultrasound for all the outcomes measured after 1, 2 or 3 week(s) of treatment (Hawkes 1986). There was no difference in patient preference for all types of thermotherapy. No harmful effects of thermotherapy were reported. REVIEWER'S CONCLUSIONS: Superficial moist heat and cryotherapy can be used as a palliative therapy. Paraffin wax baths combined with exercises can be recommended for beneficial short term effects for arthritic hands. These conclusions are limited by methodological considerations such as the poor quality of trials.

Robinson V, Brosseau L, Casimiro L, Judd M, Shea B, Wells G, Tugwell P. · Institute of Population Health, University of Ottawa, 1 Stewart Street, Ottawa, Ontario, Canada, K1N-6N5. · Cochrane Database Syst Rev. · Pubmed #11869637 No free full text.

Abstract: BACKGROUND: Thermotherapy is often used as adjunct in the treatment of rheumatoid arthritis (RA) by rehabilitation specialists. OBJECTIVES: To evaluate the effectiveness of different thermotherapy applications on objective and subjective measures of disease activity in patients with RA. SEARCH STRATEGY: We searched Medline, EMBASE, Pedro, Current Contents, Sports Discus and CINAHL up to and including September 2001. The Cochrane Field of Rehabilitation and related therapies and the Cochrane Musculoskeletal Review Group were also contacted for a search of their specialized registers. Hand searching was conducted on all retrieved articles for additional articles. SELECTION CRITERIA: Comparative controlled studies, such as randomized controlled trials, controlled clinical trials, cohort studies or case/control studies, of thermotherapy compared to control or active interventions in patients with RA were eligible. No language restrictions were applied. Abstracts were accepted. DATA COLLECTION AND ANALYSIS: Two independent reviewers identified potential articles from the literature search (VR, LB). These reviewers extracted data using pre-defined extraction forms. Consensus was reached on all data extraction. Quality was assessed by two reviewers using a 5 point scale that measured the quality of randomization, double-blinding and description of withdrawals. MAIN RESULTS: Seven studies (n=328 subjects) met the inclusion criteria. The results of this systematic review of thermotherapy for RA found that there was no significant effect of hot and ice packs applications (Ivey 1994), cryotherapy (Rembe 1970) and faradic baths (Hawkes 1986) on objective measures of disease activity including joint swelling, pain, medication intake, range of motion (ROM), grip strength, hand function compared to a control (no treatment) or active therapy. There is no significant difference between wax and therapeutic ultrasound as well as between wax and faradic bath combined to ultrasound for all the outcomes measured after 1, 2 or 3 week(s) of treatment (Hawkes 1986). There was no difference in patient preference for all types of thermotherapy. No harmful effects of thermotherapy were reported. REVIEWER'S CONCLUSIONS: Superficial moist heat and cryotherapy can be used as a palliative therapy. Paraffin wax baths combined with exercises can be recommended for beneficial short term effects for arthritic hands. These conclusions are limited by methodological considerations such as the poor quality of trials.

Welch V, Brosseau L, Shea B, McGowan J, Wells G, Tugwell P. · Clinical Epidemiology Unit, Ottawa Hospital - Civic Campus - F6, 1053 Carling Avenue, Ottawa, Ontario, Canada, K1Y-4E9. · Cochrane Database Syst Rev. · Pubmed #11406046 No free full text.

Abstract: BACKGROUND: Heat and cold therapy are often used as adjuncts in the treatment of rheumatoid arthritis by rehabilitation specialists. OBJECTIVES: To evaluate the effects of heat and cold on objective and subjective measures of disease activity in patients with rheumatoid arthritis. SEARCH STRATEGY: We searched Medline, Embase, PEDro, Current Contents, Sports Discus and CINAHL up to June 2000. The Cochrane Field of Rehabilitation and related therapies and the Cochrane Musculoskeletal Review Group were also contacted for a search of their specialized registers. Handsearching was conducted on all retrieved articles for additional articles. SELECTION CRITERIA: Randomized or controlled clinical trials of ice or heat compared to placebo or active interventions in patients with rheumatoid arthritis and case-control and cohort studies were eligible. No language restrictions were applied. Abstracts were accepted. DATA COLLECTION AND ANALYSIS: Two independent reviewers identified potential articles from the literature search. These reviewers extracted data using pre-defined extraction forms. Consensus was reached on all data extraction. Quality was assessed by two reviewers using a 5 point scale that measured the quality of randomization, double-blinding and description of withdrawals. MAIN RESULTS: Three studies (79 subjects) met the inclusion criteria. There was no effect on objective measures of disease activity (including inflammation, pain and x-ray measured joint destruction) of either ice versus control or heat versus control. Patients reported that they preferred heat therapy to no therapy (94% prefer heat therapy to no therapy). There was no difference in patient preference for heat or ice. No harmful effects of ice or heat were reported. REVIEWER'S CONCLUSIONS: Since patients preferred thermotherapy to no therapy, thermotherapy can be used as a palliative therapy which can be applied at home as needed to relieve pain. These results are limited by the poor methodological quality of the trials.

Tugwell P, Welch V, Suarez-Almazor M, Shea B, Wells G. · Department of Medicine, Ottawa Hospital-General Campus, LM-12, 501 Smyth Road, Ottawa, Ontario, Canada. · Ann Rheum Dis. · Pubmed #11053083 links to  free full text

This publication has no abstract.

Welch V, Brosseau L, Shea B, McGowan J, Wells G, Tugwell P. · Clinical Epidemiology Unit, Ottawa Hospital - Civic Campus - F6, 1053 Carling Avenue, Ottawa, Ontario, Canada, K1Y-4E9. · Cochrane Database Syst Rev. · Pubmed #11034770 No free full text.

Abstract: BACKGROUND: Heat and cold therapy are often used as adjuncts in the treatment of rheumatoid arthritis by rehabilitation specialists. OBJECTIVES: To evaluate the effects of heat and cold on objective and subjective measures of disease activity in patients with rheumatoid arthritis. SEARCH STRATEGY: We searched Medline, Embase, PEDro, Current Contents, Sports Discus and CINAHL up to June 2000. The Cochrane Field of Rehabilitation and related therapies and the Cochrane Musculoskeletal Review Group were also contacted for a search of their specialized registers. Handsearching was conducted on all retrieved articles for additional articles. SELECTION CRITERIA: Randomized or controlled clinical trials of ice or heat compared to placebo or active interventions in patients with rheumatoid arthritis and case-control and cohort studies were eligible. No language restrictions were applied. Abstracts were accepted. DATA COLLECTION AND ANALYSIS: Two independent reviewers identified potential articles from the literature search. These reviewers extracted data using pre-defined extraction forms. Consensus was reached on all data extraction. Quality was assessed by two reviewers using a 5 point scale that measured the quality of randomization, double-blinding and description of withdrawals. MAIN RESULTS: Three studies (79 subjects) met the inclusion criteria. There was no effect on objective measures of disease activity (including inflammation, pain and x-ray measured joint destruction) of either ice versus control or heat versus control. Patients reported that they preferred heat therapy to no therapy (94% like heat therapy better than no therapy). There was no difference in patient preference for heat or ice. No harmful effects of ice or heat were reported. REVIEWER'S CONCLUSIONS: Since patients enjoy thermotherapy, and there are no harmful effects, thermotherapy should be recommended as a therapy which can be applied at home as needed to relieve pain. There is no need for further research on the effects of heat or cold for RA.