DESTIN, FLA. – Bosentan, which has been shown to prevent digital ulcers in systemic sclerosis, also may have beneficial effects on skin fibrosis.
In a small, prospective, open-label study, treatment with the dual endothelin receptor antagonist was associated with a significant reduction in skin thickening as measured by the modified Rodnan skin score (mRSS), Dr. Annegret Kuhn said at the Congress of Clinical Rheumatology.
The mean change from baseline in the mRSS in the 10 systemic sclerosis patients in the study was 6.4 points on the 0-51 point scale, said Dr. Kuhn of Westfälische Wilhelms-Universität Münster (Germany).
Significant responses were seen in patients with both diffuse and limited disease, and there also was significant healing of digital ulcers. No differences were seen from baseline and week 24, however, on 20-MHz ultrasound, fist-closure evaluation, U.K. systemic sclerosis functional score, or the modified sclerosis health assessment questionnaire (SHAQ) and its visual analogue scale (Rheumatology [Oxford] 2010;49:1336-45).
Patients were treated with 62.5 mg of bosentan twice daily for 4 weeks, then with 125 mg twice daily for 20 weeks. This regimen is similar to the dosing used in the RAPIDS-1 and -2 (Randomized Placebo-Controlled Study on Prevention of Ischemic Digital Ulcers in Systemic Scleroderma–1 and –2) trials, which demonstrated the drug’s efficacy for the prevention of digital ulcers. Bosentan is currently approved for use in the United States for pulmonary artery hypertension, and – based on the RAPIDS-1 trial (Arthritis Rheum. 2004;50:3985-93) – it was also approved in Europe in 2007 for prevention of digital ulcers.
The RAPIDS-2 trial that was published this year (Ann. Rheum. Dis. 2011;70:32-8), included treatment for at least 24 weeks, and confirmed the preventive effects seen in RAPIDS-1. Bosentan was not found in either trial to be associated with improved healing in existing ulcers, however.
"Iloprost remains the best treatment for digital ulcers in systemic scleroderma," Dr. Kuhn said,
But bosentan is recommended for prevention, and it may also improve fibrosis, she noted.
Guidelines that were developed this year by a group of German experts on scleroderma call for first-line treatment with iloprost for the healing of existing ulcers, with repeated infusions for long-term care. They also call for the use of bosentan for prevention, and note that current experimental treatments include sildenafil and atorvastatin, she said.
Treatment of underlying disease (such as Raynaud’s phenomenon, vasculopathy, and the like) is also important, as are general preventive measures including nicotine abstinence, cold protection, physical treatments, lymphatic draining, elimination of sympathomimetics, and vasoconstrictors.
Topical treatments can include antiseptic agents, becaplermin gel, hydrocolloid membrane, topical lidocaine, and vitamin E gel, according to the guidelines.
Dr. Kuhn had no disclosures to report.