Low‐dose methotrexate compared with auranofin in adult rheumatoid arthritis

Self Cite

Objective. To determine the effects of drug therapy (methotrexate [MTX] versus auranofin [AUR]) onradiographic progression in patients with active rheumatoid arthritis (RA).Methods. We conducted a 9-month randomized, multicenter, double-blind trial comparing MTX and AUR. Standardized radiographs of the hands and wrists were obtained at baseline and at completion of the study. Four experienced bone radiologists graded the radiographs for erosions, joint space narrowing, erosion healing, and reparative bone formation. Conclusion. The rate of radiographic progression in patients with RA, as measured by erosion score and joint space narrowing score, was demonstrated to be lower in those treated with MTX, as compared with AUR, over a 36-week period.The rate of radiographic progression is considered to be an important parameter of the efficacy of second-line therapy in rheumatoid arthritis (RA). Whether any second-line therapy in current use, including methotrexate (MTX), slows radiographic progression is uncertain (1,2). The clinical efficacy profile of MTX is, however, favorable, based on data from short-term randomized placebo-controlled trials (3-3, comparative studies with other second-line therapies ( 6 4 , and long-term prospective studies (9,lO). In a previously published report we described the clinical results of a 36-week multicenter study comparing MTX and auranofin (AUR) (11). The effect of treatment on radiographic activity has now been evaluated PATIENTS AND METHODSPatients. Two hundred eighty-one patients with active RA were enrolled in a multicenter double-blind trial comparing MTX and AUR (1 1). All patients had had inadequate disease response to at least 2 nonsteroidal antiinflammatory drugs (NSAIDs). Patients who had received prior treatment, of any duration, with gold salts, MTX, D-penicillamine, or cytotoxic agents were excluded from the study.Patients were randomized to receive either AUR (n = 143) or MTX (n = 138) for 9 months. (At 1 of the sites, only 1 patient was enrolled in the AUR group, and that patient was excluded from the efficacy analysis.) The initial dosage of AUR was 6 mg/day; this could be increased to 9 mg/day after 24 weeks of treatment, if there was a lack of a beneficial response with the lower dosage. The initial dosage of MTX was 7.5 mg/week, which could be increased to 15 mg/week between weeks 6 and 12 in patients who had not shown a clinical response. Patients were allowed to continue taking stable maintenance doses of background NSAIDs and/or prednisone (at a maximum dosage of 10 mg/day). Standard clinical assessments of arthritis activity were performed during the trial.Radiographic evaluation. Radiographs of the hands and wrists were obtained at baseline and at completion of the 9-month trial. A standardized protocol was used for obtaining these radiographs. All radiographs were taken on a single 30 X 35-cm cassette, with the patient in a posteroanterior position with the fingers slightly separated and the forearms flat. Each study center was provided with a Kodak (Ea...

Section: Discussionmentioning

confidence: 69%

The effects of drug therapy on radiographic progression of rheumatoid arthritis. results of a 36‐week randomized trial comparing methotrexate and auranofin

Weinblatt

Polisson

Blotner

et al. 1993

Self Cite

“…This long-term open study was an extension of our previous study comparing MTX and auranofin, in which MTX was found to be not only more effective, but also less toxic than auranofin over a 36-week period (3). Following completion of the randomized trial, 123 patients were enrolled in this 5-year open extension study of MTX.…”

Section: Discussionmentioning

confidence: 99%

“…During the open study, adjustments in the MTX dosage were allowed; the maximum dosage was 20 mglweek. Clinical evaluations were performed every 12 weeks and included determinations of the number of painful joints, number of swollen joints, joint tendernesdpain index, joint swelling index, duration of morning stiffness, and patient and physician global assessments (3). A modified Stanford Health Assessment Questionnaire (MHAQ) (4) was completed at baseline, yearly, and at the last study visit.…”

Section: Methodsmentioning

confidence: 99%

Methotrexate in rheumatoid arthritis. a five‐year prospective multicenter study

Weinblatt

Kaplan

Germain

et al. 1994

Self Cite

196

Objective. To evaluate the efficacy and tolerability of oral methotrexate (MTX) in rheumatoid arthritis (RA) in a long-term prospective trial.Methods. One hundred twenty-three patients with RA who completed a 9-month multicenter randomized trial comparing MTX and auranofin enrolled in this 5-year prospective study of MTX.Results. Significant (P = 0.OOOl) improvement compared with baseline was noted in all clinical disease variables, functional status, and the Westergren erythrocyte sedimentation rate (ESR). "Marked improvement" occurred in 87 (71%) and 85 (69%) of the patients, respectively, in the joint paidtenderness index and the joint swelling index at the last evaluable visit. Forty-four patients (36%) withdrew during the study. Eight (7%) withdrew due to lack of efficacy, and 8 (7%) due to adverse experiences, including 1 patient with cirrhosis. At 5 years, 64% of patients were still taking MTX and completed the study.

“…One of these (Schmid FR et al: unpublished observations) was a small unpublished trial, and its exclusion does not affect analytic results. Since we wished to choose regimens that offered as large as possible an efficacy difference between drug and placebo, we excluded 1 auranofin arm in 1 trial, since evidence (11,12) suggests it is relatively weak. Six of the 7 ACR core set measures were included in these trials, but like many completed RA trials, 4 of the 5 trials did not include an assessment of functional status.…”

Section: Methodsmentioning

confidence: 99%

American college of rheumatology preliminary definition of improvement in rheumatoid arthritis

Felson¹,

Anderson²,

Boers³

et al. 1995

Self Cite

2,362

1,426

Objective. Trials of rheumatoid arthritis (RA) treatments report the average response in multiple outcome measures for treated patients. It is more clinically relevant to test whether individual patients improve with treatment, and this identifies a single primary efficacy measure. Multiple definitions of improvement are currently in use in different trials. The goal of this study was to promulgate a single definition for use in RA trials. Methods. Using the American College of Rheumatology (ACR) core set of outcome measures for RA trials, we tested 40 different definitions of improvement, using a 3‐step process. First, we performed a survey of rheumatologists, using actual patient cases from trials, to evaluate which definitions corresponded best to rheumatologists' impressions of improvement, eliminating most candidate definitions of improvement. Second, we tested 20 remaining definitions to determine which maximally discriminated effective treatment from placebo treatment and also minimized placebo response rates. With 8 candidate definitions of improvement remaining, we tested to see which were easiest to use and were best in accord with rheumatologists' impressions of improvement. Results. The following definition of improvement was selected: 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: patient and physician global assessments, pain, disability, and an acutephase reactant. Additional validation of this definition was carried out in a comparative trial, and the results suggest that the definition is statistically powerful and does not identify a large percentage of placebo‐treated patients as being improved. Conclusion. We present a definition of improvement which we hope will be used widely in RA trials.