Bosentan treatment of digital ulcers related to systemic sclerosis: results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial
Open Access
- 30 August 2010
- journal article
- research article
- Published by BMJ in Annals Of The Rheumatic Diseases
- Vol. 70 (1), 32-38
- https://doi.org/10.1136/ard.2010.130658
Abstract
Objectives Ischaemic digital ulcers (DUs) are common in patients with systemic sclerosis (SSc) and are a cause of disease-related morbidity. In an earlier trial, treatment with bosentan, an oral endothelin receptor antagonist, reduced the occurrence of new DUs by 48%. The present study (RAPIDS-2, for ‘RAndomized, double-blind, Placebo-controlled study with bosentan on healing and prevention of Ischemic Digital ulcers in patients with systemic Sclerosis’) was conducted to more fully evaluate the effects of bosentan treatment on DUs associated with SSc. Methods This double-blind, placebo-controlled trial conducted at 41 centres in Europe and North America randomised 188 patients with SSc with at least 1 active DU (‘cardinal ulcer’) to bosentan 62.5 mg twice daily for 4 weeks and 125 mg twice daily thereafter for 20 weeks (n=98) or matching placebo (n=90; total 24 weeks). The two primary end points were the number of new DUs and the time to healing of the cardinal ulcer. Secondary end points included pain, disability and safety. Results Over 24 weeks, bosentan treatment was associated with a 30% reduction in the number of new DUs compared with placebo (mean±standard error: 1.9±0.2 vs 2.7±0.3 new ulcers; p=0.04). This effect was greater in patients who entered the trial with more DUs. There was no difference between treatments in healing rate of the cardinal ulcer or secondary end points of pain and disability. Peripheral oedema and elevated aminotransferases were associated with bosentan treatment. Conclusions Bosentan treatment reduced the occurrence of new DUs in patients with SSc but had no effect on DU healing. Bosentan was well tolerated and may be a useful adjunct in the management of patients with SSc with recurrent DUs.Keywords
This publication has 20 references indexed in Scilit:
- Vascular Disease in SclerodermaClinical Reviews in Allergy & Immunology, 2008
- Faculty Opinions recommendation of Statins: potentially useful in therapy of systemic sclerosis-related Raynaud's phenomenon and digital ulcers.Published by H1 Connect ,2008
- Natural history of ischemic digital ulcers in systemic sclerosis: single-center retrospective longitudinal study.2007
- Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials And Research group databaseAnnals Of The Rheumatic Diseases, 2007
- Patient perception of UK scleroderma services--results of an anonymous questionnaireRheumatology, 2006
- Digital ulcers: overt vascular disease in systemic sclerosisRheumatology, 2006
- Systemic SclerosisMedicine, 2002
- Continuous Intravenous Epoprostenol for Pulmonary Hypertension Due to the Scleroderma Spectrum of DiseaseAnnals of Internal Medicine, 2000
- Intravenous iloprost treatment of Raynaud's phenomenon and ischemic ulcers secondary to systemic sclerosis.1992
- Comparison of intravenous infusions of iloprost and oral nifedipine in treatment of Raynaud's phenomenon in patients with systemic sclerosis: a double blind randomised study.BMJ, 1989