Objective Early diffuse scleroderma (systemic sclerosis; SSc) has no proven treatment. This study was undertaken to examine the efficacy of methotrexate (MTX) in improving the skin and other disease parameters in early diffuse SSc. Methods Seventy‐one patients with diffuse SSc of <3 years' duration were enrolled in a multicenter, randomized, placebo‐controlled, double‐blind trial. Thirty‐five patients were treated with MTX and 36 with placebo. Treatment was administered for 12 months. The primary outcome measures were skin score (as determined with 2 different indices) and physician global assessment. Results At baseline, there were no statistically significant differences in skin scores, carbon monoxide diffusing capacity (DLCO), physician global assessment, or other secondary outcome measurements between the 2 treatment groups. At study completion, results slightly favored the MTX group (mean ± SEM modified Rodnan skin score 21.4 ± 2.8 in the MTX group versus 26.3 ± 2.1 in the placebo group [P < 0.17]; UCLA skin score 8.8 ± 1.2 in the MTX group versus 11.0 ± 0.9 in the placebo group [P < 0.15]; DLCO in the MTX group 75.7 ± 4.6 versus 61.8 ± 3.4 in the placebo group [P < 0.2]). In addition, physician global assessment results favored MTX (P < 0.035), whereas patient global assessment did not differ significantly between groups. When between‐group differences for changes in scores from baseline to 12 months were examined using intent‐to‐treat methodology, MTX appeared to have a favorable effect on skin scores (modified Rodnan score −4.3 in the MTX group versus 1.8 in the placebo group [P < 0.009]; UCLA score −1.2 in the MTX group versus 1.2 in the placebo group [P < 0.02]), but differences in the degree of change in the DLCO and physician global assessment were not significant. For the UCLA skin score, these differences in results were not statistically significant after adjustment for baseline differences in sex distribution and steroid use. Dropout rates were similar in the 2 groups. Conclusion Although results of this trial demonstrated a trend in favor of MTX versus placebo in the treatment of early diffuse SSc, the between‐group differences were small and the power to rule out false‐negative results was only 50%. Our findings do not provide evidence that MTX is significantly effective in the treatment of early diffuse SSc.

There are differences in lupus phenotypes between ethnic populations. Although ethnicity was not found to be a significant independent predictor of damage accrual, low income was.

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The ability of antimalarials to moderate severe disease activity in systemic lupus erythematosus (SLE) is plausible but undemonstrated. We evaluated the long-term effectiveness of maintaining treatment with hydroxychloroquine sulphate (HCQ) to prevent major flares in quiescent SLE. Forty-seven patients with quiescent SLE who had been randomized to take HCQ (n = 25) or placebo (n = 22) as part of a 24-week withdrawal trial were evaluated for an additional 3 years. The primary outcome was time to a major flare of SLE which resulted in either the institution of or an increase in the current dosage of prednisone of 10 mg/day or more, or institution of therapy with immunosuppressive agents. Secondary outcomes included the specific subtype of these major flares (glomerulonephritis, vasculitis or other) and hospitalization for an exacerbation of SLE. An intent-to-treat analysis was conducted. Over the 42 months of study, 11 of 22 (50%) patients randomized initially to placebo, and seven of 25 (28%) patients randomized to continue treatment experienced a major flare. The relative risk of major flare for those randomized to continue HCQ compared with controls was 0.43 (95% CI: 0.17, 1.12). The relative risks for subtypes of flares were 0.26 (95% CI: 0.03, 2.54) for nephritis, 0.51 (95% CI: 0.09, 3.08) for vasculitis and 0.65 (95% CI: 0.17, 2.41) for flares characterized by other symptoms. The relative risk of hospitalization for major flare for patients randomized to continue hydroxychloroquine was 0.58 (95% CI: 0.13, 2.60). While the results are not statistically significant, they are compatible with the clinical belief that HCQ has a long-term protective effect against major disease flares in SLE and suggest that on average, HCQ use reduces major flares by 57% (95% CI: 83% reduction to 12% increase).