Objective: To assess the safety and efficacy of rapamycin in the treatment of diffuse systemic sclerosis (SSc; scleroderma).
Methods: Eighteen patients with diffuse SSc of <or=5 years duration were randomized to receive rapamycin or methotrexate (MTX) in a single-blind, 48-week study. Abnormalities in clinical and laboratory parameters were compared between the 2 treatment groups. The potential efficacy of the study drugs was evaluated by comparing results of the baseline and 48-week assessments, including the modified Rodnan skin thickness score (MRSS) and the Health Assessment Questionnaire disability index.
Results: The baseline characteristics of the patients were similar in both groups (n=9 in each). One patient in the rapamycin group who never received the study drug was excluded from the analysis. Three patients in each group withdrew from the study; 2 of the withdrawals were treatment-related (severe hypertriglyceridemia associated with rapamycin, and pancytopenia associated with MTX), and 4 were SSc-related. Hypertriglyceridemia was the most notable side effect associated with rapamycin, but it was generally well tolerated and treatable. The incidence and severity of other adverse drug reactions were comparable between the 2 groups. Within each group, the MRSS improved significantly from baseline. In the rapamycin group, the patient's global assessment showed a significant improvement from baseline, while forced vital capacity values declined from baseline. The disease activity scores at 48 weeks and the changes in these scores from baseline were not significantly different between the 2 groups.
Conclusion: Rapamycin has a reasonable safety profile in a select group of patients with scleroderma. Larger trials are needed to assess the efficacy of rapamycin in patients with early diffuse SSc.