Outcome Measure In Rheumatoid Arthritis Research Articles

Auranofin versus placebo in rheumatoid arthritis.

Auranofin is an oral gold compound used for the treatment of rheumatoid arthritis RA. The use of auranofin has declined in the past few years, perhaps due in part to conflicting results from different studies. To estimate the short-term efficacy and toxicity of auranofin for the treatment of (RA) SEARCH STRATEGY: We searched MEDLINE and EMBASE up to December 1998, the Cochrane Controlled Trials Register (CCTR) version 4, 1998, and the Cochrane Musculoskeletal Group Specialized Register. A hand search was also done of the reference lists of the trials retrieved from the electronic search. All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing auranofin against placebo in patients with RA DATA COLLECTION AND ANALYSIS: The methodological quality of the trials was assessed using a validated assessment tool (Jadad 1996). Rheumatoid arthritis outcome measures were extracted from the publications for the 6-month endpoint. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts, pain and global assessments. The weighted mean difference (WMD) was used for ESR. Toxicity was evaluated with pooled odds ratios for withdrawals and adverse reactions. A chi-square test was used to assess heterogeneity among trials. In the presence of heterogeneity, random effects models were used. Otherwise, the data was pooled assuming fixed effects. A statistically significant benefit was observed for auranofin when compared to placebo for tender joint scores, pain, patient and physician global assessments and ESR. The SMD between treatment and placebo was -0.39 (95% CI -0.54, -0.25) for tender joint scores, -0.08 (95% CI -0.22, -0.07) for swollen joint scores, and the WMD was -4.68 (95% CI -6.59, -2.77) for pain scores and -9.85mm (95% CI -16.46, -3.25) for ESR. Withdrawals from adverse reactions were 1.5 times higher in the auranofin group OR = 1.52 (95% CI 0.94, 2.46) but this result was not statistically significant. Patients receiving placebo were three times more likely to discontinue treatment because of lack of efficacy than patients receiving auranofin: OR=0.31 (95% CI: 0.21, 0.44). Auranofin appears to have a small clinically and statistically significant benefit on the disease activity of patients with RA. The beneficial effects appear to be modest compared to drugs such as methotrexate or parenteral gold. Its effects on long term health status and radiological progression are not clear at this time.

Gait variables: appropriate objective outcome measures in rheumatoid arthritis.

To assess the reliability and responsiveness of gait speed, cadence and stride length at two self-selected speeds (SSS) in subjects with rheumatoid arthritis (RA). Thirty-one subjects with RA were assessed on three occasions. At each assessment session, subjects were asked to self-report walk pain on visual analogue scales, rate physical function using the Health Assessment Questionnaire, and walk five times at both a normal SSS and a fast SSS along an 8 m electric footswitch walkway. Despite stability of pain and physical function, there were significant gait changes from the first to the second assessment session at the normal SSS, although this 'learning' effect was not evident at either SSS between the second and the third assessment session. If the recommended protocol is followed, quantitative gait variables can provide reliable and responsive outcome measures in this population for use in evaluating therapeutic interventions.

Disease modification in rheumatoid arthritis with leflunomide

Rheumatoid arthritis (RA) is characterized by chronic inflammation and irreversible destruction of articular cartilage and bone. Disease progression as assessed by radiographic imaging of structural joint damage is a key outcome measure in RA. Joint damage is especially rapid during early phases of RA, thus the current trend of early aggressive therapy with disease-modifying antirheumatic drugs (DMARDs). Radiographic analysis of disease progression with the novel DMARD leflunomide was compared to methotrexate and sulfasalazine in two large, placebo-controlled, randomized Phase III studies ( N = 580). The results as indicated by changes in x-ray scores indicate that leflunomide and both active comparators slow disease progression significantly better than placebo ( P h 0.01). Slowing of disease progression with leflunomide was similar to sulfasalazine at 6 months but better than methotrexate ( P h 0.049) at 12 months. These data verify the ability of leflunomide to slow disease progression and confirm its disease-modifying potential.

Omega-3 fatty acids in rheumatoid arthritis: an overview

Objectives: To review background, pharmacological properties, mechanisms ofaction, and published clinical experience using omega-3 fatty acids in rheumatoid arthritis. Materials and Methods: English language publications were identified through a computerized search (using MEDLINE) between 1979 and 1995 using the terms “omega-3 fatty acids” and “fish oil.” In addition, manual search and cross references were used to obtain published articles on the subject. Papers showing evidence of pharmacological properties and mechanisms of action were analyzed. For therapeutic efficacy, only randomized clinical trials are presented in this article. All papers were reviewed by a board certified rheumatologist with training in research methodology and critical appraisal skills. He was aware of study objectives. Results: Main results are summarized in the text and presented in tables. Mean change from baseline is presented only for patients treated with omega-3 fatty acids. Omega-3 fatty acids are superior with respect to placebo in improving some outcome measures, and decrease the long-term requirements for nonsteroidal antiinflammatory drugs. Some of these effects are statistically significant, but their clinical significance remain to be established. Conclusions: Treatment with omega-3 fatty acids has been associated with improvement in some outcome measures in rheumatoid arthritis. Studies are needed to determine if they might represent an alternative to nonsteroidal antiinflammatory drugs in certain circumstances.

Methotrexate for rheumatoid arthritis.

To estimate the short-term efficacy and toxicity of methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). We searched the Cochrane Musculoskeletal Group trials register, and Medline, up to July 1997, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). The search was complemented with bibliography searching of the reference list of the trials retrieved from the electronic search. Key experts in the area were contacted for further published and unpublished articles. Randomized controlled trials and controlled clinical trials comparing MTX against placebo in patients with RA. Two reviewers determined the studies to be included based on inclusion and exclusion criteria (GW, MSA). Data were independently abstracted by two reviewers (EB, MSA), and checked by a third reviewer (BS) using a pre-developed form for the rheumatoid arthritis sub-group of the Cochrane Musculoskeletal Group. The same two reviewers, using a validated scale (Jadad 1996) assessed the methodological quality of the trials independently. Rheumatoid arthritis outcome measures were extracted from the publications. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts, pain, and global and functional assessments. Weighted mean differences (WMDs) were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios (OR) for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout and random effects for outcomes showing heterogeneity. Five trials and 300 patients were included. A statistically significant benefit was observed for MTX when compared to placebo. Statistically significant differences were observed for all measures except ESR. The standardized weighted difference (effect size) between MTX and placebo for the various outcome measures varied between -0.43 and -1.5. No differences were observed in the total number of withdrawals and dropouts (OR = 0.95), although patients on MTX were three times more likely to discontinue treatment because of adverse reactions (OR=3.47) and four times less likely to withdraw due to lack of response (OR=0.22). Twenty-two percent of people on MTX withdrew due to adverse effects compared to seven percent of the placebo group. MTX has a substantial clinically and statistically significant benefit in the short term treatment of patients with RA.

Cyclosporine for rheumatoid arthritis.

To estimate the short-term (up to one year) effects of cyclosporine for rheumatoid arthritis. We searched the Cochrane Musculoskeletal Group trials register, and Medline, up to 1997, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). The search was complemented with bibliography searching of the reference list of the trials retrieved from the electronic search. Key experts in the area were contacted for further published and unpublished articles. All randomized clinical trials (RCTs) and controlled clinical trials (CCTs) comparing cyclosporine against placebo in patients with rheumatoid arthritis. Two reviewers determined the trials to be included based on inclusion and exclusion criteria (GW, MSA). Data were independently abstracted by two reviewers (DH, GW),and checked by a third reviewer (BS) using a pre-developed form for the rheumatoid arthritis sub-group of the Cochrane Musculoskeletal Group. Methodological quality of the RCTs and CCTs was assessed by two reviewers (BS, DH). Rheumatoid arthritis outcome measures were extracted from the publications for change from baseline endpoints. Sufficient data were obtained to include in the pooled analysis the number of swollen joints, physician global assessment, patient global assessment and erythrocyte sedimentation rate (ESR). Three trials and 318 patients were included. A statistically significant decrease in the number of tender and swollen joints was observed for cyclosporine when compared to placebo. The standardized mean difference (SMD) for the change in the number of swollen joints was -0.969. Significant improvements in pain and the functional index were also found for cyclosporine. More side effects occurred in the cyclosporine group compared to placebo. Cyclosporine has an important clinical benefit int the short-term (up to one year) treatment of patients with progressive rheumatoid arthritis.

Sulfasalazine for rheumatoid arthritis.

To estimate the short-term efficacy and toxicity of sulfasalazine for the treatment of rheumatoid arthritis (RA). We searched the Cochrane Musculoskeletal Group trials register, and Medline, up to July 1997, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). The search was complemented with bibliography searching of the reference list of the trials retrieved from the electronic search. Key experts in the area were contacted for further published and unpublished articles. All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing sulfasalazine against placebo in patients with RA. Two reviewers determined the studies to be included based on inclusion and exclusion criteria (GW, MSA). Data were independently abstracted by two reviewers (EB, MSA), and checked by a third reviewer (BS) using a pre-developed form for the rheumatoid arthritis sub-group of the Cochrane Musculoskeletal Group. The same two reviewers, using a validated scale (Jadad 1996) assessed the methodological quality of the RCTs and CCTs independently. Rheumatoid arthritis outcome measures were extracted from the publications. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts, pain, and global and functional assessments. Weighted mean differences (WMDs) were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios (OR) for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout and random effects for outcomes showing heterogeneity. Six trials, including 468 patients were included. A statistically significant benefit was observed for sulfasalazine when compared to placebo for tender and swollen joint scores, pain and ESR. The standardized weighted mean difference between treatment and placebo was -0.49 for tender and swollen joint scores, and -0.42 for pain. The difference for ESR was -17.6mm. Withdrawals from adverse reactions were significantly higher in the sulfasalazine group (OR=3.0). Patients receiving placebo were four times more likely to discontinue treatment because of lack of efficacy than patients receiving sulfasalazine. Sulfasalazine appears to have a clinically and statistically significant benefit on the disease activity of patients with RA. Its effects on overall health status and radiological progression are not clear at this time, but would appear to be modest.

Injectable gold for rheumatoid arthritis.

To estimate the short-term benefit and risk of side-effects of injectable gold for rheumatoid arthritis. We searched the Cochrane Musculoskeletal Group trials register, and Medline, up to July 1997, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). The search was complemented with bibliography searching of the reference list of the trials retrieved from the electronic search. Key experts in the area were contacted for further published and unpublished articles. Randomized clinical trials (RCT) comparing injectable gold against placebo in patients with rheumatoid arthritis were included. Methodological quality of the RCTs was asessed by two reviewers (MS, BS) (kappa=1.0). Rheumatoid arthritis outcome measures were extracted by two reviewers from the publications for the 6 month endpoint. Sufficient data was obtained to conduct a pooled analysis of the number of swollen joints, physician global assessment, patient global assessment and erythrocyte sedimentation rate (ESR). Results were analyzed as standardized weighted mean differences for swollen joints and global assessments and weighted mean differences for ESR. Toxicity was evaluated with pooled odds ratios for withdrawals. Heterogeneity was estimated using a chi-square test. Fixed effects models were used throughout. Four trials and 415 patients were included. A statistically significant benefit was observed for injectable gold when compared to placebo. The standardized weighted difference (effect size) between gold and placebo for the number of swollen joints was -0.5, translating into a percentage change of 30% in favour of gold adjusted for placebo. Statistically significant differences were also observed for ESR and patient and physician assessments. Twenty two percent of the treated patients withdrew from toxicity compared to 4% of controls (OR=3.9 - 95%Cl: 2.1 - 7.2). Although its use can be limited by the incidence of serious toxicity, injectable gold has an important clinically and statistically significant benefit in the short term treatment of patients with rheumatoid arthritis.

Video image analysis of hands: development of an 'anatomic index' as a potential outcome measure in rheumatoid arthritis.

In this study, we used video image analysis for the measurement of hand dimensions to reflect destructive changes in rheumatoid arthritis. Thirteen dimensions were measured from anteroposterior and lateral views of the hands, open and closed. Comparison of measurements in 19 patients and 19 control subjects showed significant differences for nine of the 13 measurements. Five were reproducible on retesting in a subset of patients and normals. Two were eliminated because they were similar to other measurements. The three remaining measurements selected for differentiation of patients and normals, and reproducibility, were combined in an arbitrary 'anatomic index'. This enhanced separation of normals and patients with rheumatoid arthritis. The results demonstrate that measurement of certain hand dimensions and their combination in an 'anatomic index' could provide a measure reflecting the progressive anatomical abnormality caused by rheumatoid arthritis. Validation of this concept could provide a further outcome measure in patients with rheumatoid arthritis.

Outcome measures in RA - reducing the ???signal-to-noise??? ratio

Outcome measures in rheumatoid arthritis (RA) are important in both the clinical situation and in the evaluation of new treatments. The most appropriate clinical measures for use in these settings and the current opinion regarding how these measures may be improved was recently discussed at the 12th Annual General Meeting of the British Society for Rheumatology [Glasgow, UK; April 1995].

The social dimension of health status measures in rheumatoid arthritis

Fifty-six patients with rheumatoid arthritis (RA) were assessed on two occasions three months apart. They completed two health status instruments--the Arthritis Impact Measurement Scales (AIMS) and the Nottingham Health Profile (NHP)--and the Beck Depression Inventory. In addition, clinical and serological data were gathered in order to calculate severity of disease according to the Mallya and Mace index. Health status instruments and the severity of disease index showed agreement in the assessment of mobility; similar agreement was found for different assessments of emotions. However, the two instruments provided social interaction scores with little agreement either cross-sectionally or in terms of change over time. It is argued that the generic NHP may be a valid instrument as an outcome measure in RA but the NHP and AIMS assess different aspects of social interaction. Care is needed in the selection of outcome measures to evaluate interventions.

Which traditional measures should be used in rheumatoid arthritis clinical trials?

It is standard practice to use multiple outcome measures in rheumatoid arthritis (RA) clinical trials. Because of this, multiple testing is usually done, and there is confusion in the interpretation of the results. It is not clear which measures are the most sensitive to detecting improvement and which provide independent information. To address these questions, we conducted an analysis of pooled raw data from 3 placebo-controlled RA trials: one of methotrexate, another of oral and injectable gold, and the third of low-dose and high-dose D-penicillamine. The results show that the joint tenderness count, erythrocyte sedimentation rate, grip strength, and physician assessment of disease activity perform best in RA clinical trials and cover the domain of change measured by traditional outcome measures. Other clinical measures may provide little additional useful information for a standard therapeutic trial of up to 6 months duration, and some measures, such as the proximal interphalangeal joint circumference, hemoglobin level, and 50-foot walking time, can be eliminated from such trials.

A rheumatological dilemma: is it possible to modify the course of rheumatoid arthritis? Can we answer the question?

The question 'Does the use of second-line therapy confer long-term benefit on outcome measures in rheumatoid arthritis?' remains unanswered. The major obstacle which prevents collection of the necessary data is the lack of a suitable control group. In this report experience with three 'second-line placebo groups' is described, and previous studies in the literature which incorporated a placebo group are reviewed. In the absence of concurrent corticosteroid therapy very few patients remain on placebo second-line medication after one year. Those that do, appear to have milder disease and are not representative of the group as a whole. Data on outcome measures need to be collected over two to five years, but the answer to the question which is posed does not depend upon larger and larger placebo groups which constitute increasing bias. To define the extent of benefit offered by the more powerful therapeutic agents a novel approach in regard to drug assessment will be required.