Scleroderma

Kevin Deane, MD
Posted: 03/10/2010

Experience With Rituximab in Scleroderma: Results From a 1-Year, Proof-of-Principle Study
Daoussis D, Liossis SN, Tsamandas AC, et al. Rheumatology (Oxford). 2010;49:271-280

Background
Multiple drugs have been tried in scleroderma to improve both skin disease and pulmonary disease. However, most of these studies have failed to show significant benefit. In an open-label study, Daoussis and colleagues investigated the effect of the B-cell directed agent rituximab in improving pulmonary function and skin disease in scleroderma.

Study Summary
Eight patients with scleroderma were given rituximab for 2 cycles 24 weeks apart; each cycle consisted of 375 mg/m2 weekly, for a total of 4 doses. Lung and skin measures at baseline and 1 year after treatment were compared within the group of treated patients and with results in 6 patients with scleroderma treated with other agents, including mycophenolate, corticosteroids, cyclophosphamide, and bosentan (patients receiving rituximab may have also given these agents). All patients had diffuse scleroderma, were Scl-70 positive, and had clinically significant interstitial lung disease.

The rituximab-treated patients had improvement in forced vital capacity and diffusing carbon monoxide compared with their baseline values and compared with controls. Functional status also improved in 6 rituximab-treated patients, with a decrease in Health Assessment Questionnaire score of 0.2. Finally, skin thickening improved in rituximab-treated patients compared with their baseline status, and in several patients, skin fibrosis on skin biopsy was reduced. No mortality benefit was reported. The authors conclude that rituximab may improve lung function and skin scores in patients with scleroderma, and they propose larger randomized studies to investigate further the role of rituximab in treatment of scleroderma.

Viewpoint
The failure of multiple treatments to show clinically meaningful and statistically significant improvement in scleroderma has been frustrating for those who treat this devastating disease. Evidence that B cells may be important in the pathogenesis of scleroderma[1] has served as the rationale for Daoussis and colleagues’ study, and their results are promising. However, the sample was small, and we need to be cautious in terms of how much excitement the findings generate. As the authors rightly point out, their study should serve to stimulate large, randomized placebo-controlled trials for scleroderma and stimulate further investigation into the role of B cells in the pathogenesis of this disease. Of importance will be which outcomes are assessed in future studies. Improvements in measures of lung physiology are important, but ultimately quality of life and mortality need to improve.

References
1. Lafyatis R, O'Hara C, Feghali-Bostwick CA, Matteson E. B cell infiltration in systemic sclerosis-associated interstitial lung disease. Arthritis Rheum. 2007;56:3167-3168.