Rheumatoid Arthritis: Robinson V

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.

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.

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.

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.

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.

Casimiro L, Brosseau L, Robinson V, Milne S, Judd M, Well G, Tugwell P, Shea B. · School of Rehabilitation Sciences, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada, K1H 8M5. · Cochrane Database Syst Rev. · Pubmed #12137714 No free full text.

Abstract: BACKGROUND: Ultrasound is often used, by rehabilitation specialists, as an adjunct therapy for the symptomatic treatment of rheumatoid arthritis (RA). Its mechanical energy has antiinflammatory as well as analgesic properties. OBJECTIVES: To evaluate the effects of ultrasound on objective and subjective measures of disease activity in patients with RA. SEARCH STRATEGY: A comprehensive search was conducted 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 specialized registers were also searched. 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 clinical controlled 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 5 point validated assessment tool that measures the quality of randomization, double-blinding and description of withdrawals. MAIN RESULTS: Two studies (n=80 participants) met the inclusion criteria. Ultrasound to the palmar and dorsal aspect of the hand significantly increases grip strength when compared to a control (weighted mean difference (WMD) 28.07, 95CI: 13.37 to 42.77). Ultrasound to the palmar and dorsal aspects of the hand also appears to have beneficial effects to the following outcome measures: wrist dorsal flexion (WMD 1.90, 95%CI: 0.64 to 3.16), duration of morning stiffness (WMD 28.54, 95%CI: 0.18 to 56.90), number of swollen joints (WMD 1.02, 95%CI: 0.45 to 1.59) and the number of painful joints (WMD 1.20, 95%CI: 0.45 to 1.95). There is no significant difference between a)exercises and wax, b)exercises with ultrasound, c)exercises with ultrasound and faradic hand baths for the following outcome measures: pain score, grip strength, circumference of proximal interphalangeal (PIP) joints, articular index, range of motion or level of activity. REVIEWER'S CONCLUSIONS: The reviewers concluded that ultrasound in combination with the following treatment modalities; exercises, faradic current and wax baths, is not supported and cannot be recommended. Ultrasound alone can however, be used on the hand to increase grip strength, and to a lesser extent, based on the borderline results, increase wrist dorsal flexion, decrease morning stiffness, reduce the number of swollen joints and reduce the number of painful joints. It is important to note that these conclusions are limited by the methodological considerations such as poor quality of the trials, the low number of clinical trials, and the small sample size of the included studies.

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.

Brosseau L, Milne S, Wells G, Tugwell P, Robinson V, Casimiro L, Pelland L, Noel MJ, Davis J, Drouin H. · School of Rehabilitation Sciences, University of Ottawa, Ottawa, Ontario, Canada. · J Rheumatol. · Pubmed #15517640 No free full text.

Abstract: OBJECTIVE: The objective of this metaanalysis is to examine the effectiveness of continuous passive motion (CPM) following total knee arthroplasty (TKA). METHODS: This metaanalysis used the methodology proposed by the Cochrane Collaboration. RESULTS: This review of 14 studies (952 patients) found significant improvements in active knee flexion and analgesic use 2 weeks postoperatively with the use of CPM and physiotherapy (PT) compared to PT alone. In addition, length of hospital stay and need for knee manipulations were significantly decreased in the CPM group. Not enough data were available to compare the degree of knee flexion applied or number of hours of application of CPM. However, significant results were not found for other comparisons such as short term CPM application versus longterm CPM application and wide treatment range versus small treatment range for the outcomes of active knee flexion, passive knee flexion and extension, presence of a fixed flexion deformity, use of analgesic, or total knee range of motion. CONCLUSION: CPM combined with PT may offer beneficial results for patients post-TKA. However, the potential benefits will need to be carefully weighed against the inconvenience and expense of CPM. More research is necessary to assess the differences in effectiveness with different characteristics of application such as total duration of treatment and intensity of CPM interventions.

Osiri M, Shea B, Robinson V, Suarez-Almazor M, Strand V, Tugwell P, Wells G. · Department of Medicine, Faculty of Medicine, Chulalongkorn University Hospital, Bangkok, Thailand. · J Rheumatol. · Pubmed #12784387 No free full text.

Abstract: OBJECTIVE: To systematically review the evidence from clinical trials on the efficacy and toxicity of leflunomide for the treatment of active rheumatoid arthritis (RA). METHODS: We searched Medline, Embase, Current Contents, and the Cochrane Controlled Trial Register for human randomized controlled trials (RCT) and controlled clinical trials up to December 2001. We also hand-searched reference lists and conference proceedings and consulted content experts. Relative benefit (RB), and weighted mean differences or standardized mean differences with their 95% confidence interval (95% CI) were calculated. RESULTS: Six RCT totaling 2044 patients with RA were included in this review. Using specific criteria, all trials were considered of high methodological quality. Leflunomide improved the ACR20 response rate roughly 2 times over placebo both at 6 months (RB = 1.93, 95% CI 1.51, 2.47) and at 12 months (RB = 1.99, 95% CI 1.42, 2.77). Other clinical outcomes of disease activity and function and radiological scores were also significantly better for leflunomide patients than those taking placebo. No significant differences for most of the outcomes were observed between leflunomide and sulfasalazine (SSZ) or methotrexate (MTX). Adverse events were more common in the leflunomide group, but withdrawal rates were fewer than for placebo. Overall, withdrawal rates and adverse events in the leflunomide group were not different from SSZ or MTX. CONCLUSION: Leflunomide improves all clinical outcomes and delays radiographic progression at 6 and 12 months of RA treatment compared to placebo. Its efficacy and adverse events at 2 years of treatment are comparable to SSZ and MTX. Longterm efficacy and toxicity remain to be established.

Osiri M, Suarez-Almazor ME, Wells GA, Robinson V, Tugwell P. · Department of Medicine, Chulalongkorn University Hospital, Bangkok, Thailand. · Ann Rheum Dis. · Pubmed #12634229 links to  free full text

Abstract: OBJECTIVE: To calculate the number needed to treat (NNT) and number needed to harm (NNH) from the data in rheumatology clinical trials and systematic reviews. METHODS: The NNTs for the clinically important outcome measures in the rheumatology systematic reviews from the Cochrane Library, issue 2, 2000 and in the original randomised, double blind, controlled trials were calculated. The measure used for calculating the NNT in rheumatoid arthritis (RA) interventions was the American College of Rheumatology 20% improvement or Paulus criteria; in osteoarthritis (OA) interventions, the improvement of pain; and in systemic sclerosis (SSc) interventions, the improvement of Raynaud's phenomenon. The NNH was calculated from the rate of withdrawals due to adverse events from the treatment. RESULTS: The data required for the calculation of the NNT were available in 15 systematic reviews and 11 original articles. For RA interventions, etanercept treatment for six months had the smallest NNT (1.6; 95% confidence interval (CI) 1.4 to 2.0), whereas leflunomide had the largest NNH (9.6; 95% CI 6.8 to 16.7). For OA treatment options, only etodolac and tenoxicam produced significant pain relief compared with placebo (NNT=4.4; 95% CI 2.4 to 24.4 and 3.8; 95% CI 2.5 to 7.3, respectively). For SSc interventions, none were shown to be efficacious in improving Raynaud's phenomenon because the 95% CI of the NNT was infinite. CONCLUSIONS: The NNT and NNH are helpful for clinicians, enabling them to translate the results from clinical trials and systematic reviews to use in routine clinical practice. Both NNT and NNH should be accompanied by a limited 95% CI and adjusted for the individual subject's baseline risk.