Drs. Korn, Mayes, Hachulla, Rich, Seibold, Hsu, Guillevin, Herrick, Merkel, Denton, and Black have received consultancies and/or honoraria from Actelion Pharmaceuticals Ltd.
Digital ulcers in systemic sclerosis: Prevention by treatment with bosentan, an oral endothelin receptor antagonist
Article first published online: 8 DEC 2004
Copyright © 2004 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 50, Issue 12, pages 3985–3993, December 2004
How to Cite
Korn, J. H., Mayes, M., Matucci Cerinic, M., Rainisio, M., Pope, J., Hachulla, E., Rich, E., Carpentier, P., Molitor, J., Seibold, J. R., Hsu, V., Guillevin, L., Chatterjee, S., Peter, H. H., Coppock, J., Herrick, A., Merkel, P. A., Simms, R., Denton, C. P., Furst, D., Nguyen, N., Gaitonde, M., Black, C. and RAPIDS-1 Study Group (2004), Digital ulcers in systemic sclerosis: Prevention by treatment with bosentan, an oral endothelin receptor antagonist. Arthritis & Rheumatism, 50: 3985–3993. doi: 10.1002/art.20676
- Issue published online: 8 DEC 2004
- Article first published online: 8 DEC 2004
- Manuscript Accepted: 26 AUG 2004
- Manuscript Received: 16 MAR 2004
- Actelion Pharmaceuticals Ltd.
- NIH (General Clinical Research Center grant from the National Center for Research Resources). Grant Number: M01-RR-00533
Recurrent digital ulcers are a manifestation of vascular disease in patients with systemic sclerosis (SSc; scleroderma) and lead to pain, impaired function, and tissue loss. We investigated whether treatment with the endothelin receptor antagonist, bosentan, decreased the development of new digital ulcers in patients with SSc.
This was a randomized, prospective, placebo-controlled, double-blind study of 122 patients at 17 centers in Europe and North America, evaluating the effect of treatment on prevention of digital ulcers. The primary outcome variable was the number of new digital ulcers developing during the 16-week study period. Secondary assessments included healing of existing digital ulcers and evaluation of hand function using the Scleroderma Health Assessment Questionnaire.
Patients receiving bosentan had a 48% reduction in the mean number of new ulcers during the treatment period (1.4 versus 2.7 new ulcers; P = 0.0083). Patients who had digital ulcers at the time of entry in the study were at higher risk for the development of new ulcers; in this subgroup the mean number of new ulcers was reduced from 3.6 to 1.8 (P = 0.0075). In patients receiving bosentan, a statistically significant improvement in hand function was observed. There was no difference between treatment groups in the healing of existing ulcers. Serum transaminase levels were elevated to >3-fold the upper limit of normal in bosentan-treated patients; this elevation is comparable with that observed in previous studies of this agent. Other side effects were similar in the 2 treatment groups.
Endothelins may play an important role in the pathogenesis of vascular disease in patients with SSc. Treatment with the endothelin receptor antagonist bosentan may be effective in preventing new digital ulcers and improving hand function in patients with SSc.