Scleroderma lung disease: treatment with cyclophosphamide

Abstract

Evaluation of: Tashkin, Elashoff, Clements PJ et al. Cyclophosphamide versus placebo in scleroderma lung disease. N. Engl. J. Med. 354(25), 2655-2666 (2006). Interstitial lung disease has become one of the leading causes of morbidity and mortality in systemic sclerosis. Currently, there remains a void in proven effective treatment strategies to provide clinical benefit to affected patients. The article under evaluation pioneers the efforts of investigating oral cyclophosphamide in treating scleroderma lung disease by designing a prospective, double-blinded, placebo-controlled study examining the drug's effect on outcome measures of forced vital capacity, patient subjective health assessment questionnaire disability scores, among others. We review the methods, results and overall conclusion of the study, which shows a significant, yet modest, result demonstrating the benefit of oral cyclophosphamide in the context of this disease setting. We conclude that although the study provides an excellent starting point for examining the efficacy of cyclophosphamide in certain forms of scleroderma lung disease, the study's high drop-out rate, choice of forced vital capacity as a primary outcome, side-effect profile of the drug and overall significance of the results make the conclusions difficult to incorporate into clinical practice.