Background Bosentan, an endothelin-1 receptor antagonist, is indicated in Europe since 2007 for the prevention of new digital ulcers (DU) in systemic sclerosis (SSc).
Objectives To identify modalities of bosentan use and the profile of patients receiving such preventive treatment at any time for any duration since 2007 in current practice.
Methods This retrospective observational study was conducted in 2011 in 10 French specialist centers. Patients included were adults with SSc according to ACR or Leroy-Medsger criteria, starting bosentan for prevention of DU between 2007 and 2010. Patients treated with bosentan in clinical trials and patients deceased since the start of bosentan were excluded. From the complete list of eligible patients of each center, up to 10 patients were randomly selected.
Results 89 patients (mean age, 52 years) were drawn from 130 eligible patients. Male-to-female ratio was 1/2.2. SSc was diffuse in 44% of patients; 26% had continuous corticoid therapy; 1 out of 4 was active smoker. At start of bosentan, Raynaud’s phenomenon (RP) was present for 14.7±12 years. Time since first DU episode was 6.5±7 years, but 42% of patients had recent ulcerative disease (<3 years). Prior to start of bosentan, ulcerative disease was complicated by autoamputation (7.9%), surgical amputation (5.6%), osteitis (5.6%), gangrene (4.5%). Reasons for bosentan prescription were recurring (81%), severe (64%), complicated DU (30%), and failure of other preventive measures including calcium blockers (49%). Initial bosentan dosing was 125 mg/day (n=88); 82 patients received long-term treatment with 250 mg/day. Prescription was seasonal in 6 patients. During bosentan treatment (mean duration, 19 months), out of 66 patients with complete healing of DU when bosentan was started or at any time during follow-up, 32 experienced no new DU. These patients were more likely to have a cutaneous limited form of SSc with anti-centromere antibodies. Frequencies of complications were: autoamputation 2.3%, surgical amputation 1.1%, osteitis 1.1%, gangrene 0%. In 18 patients bosentan was definitively stopped; in 6 of them for hepatic cytolysis (6.7%).
Conclusions This study has created the first national cohort of patients treated with bosentan for prevention of DU in SSc in France. Patients treated with bosentan have severe ulcerative disease, which is often resistant to other preventive measures. Among these, male patients and those with diffuse disease forms appear overrepresented. One quarter of patients present the potentially aggravating factors corticoid therapy and active smoking. In the large majority of cases target dosing of bosentan was respected; tolerance was satisfactory and comparable to results of previous studies.
Disclosure of Interest C. Agard Consultant for: Actelion°, P. Carpentier Consultant for: Actelion°, L. Mouthon Grant/Research support from: Actelion°, Consultant for: Actelion°, P. Clerson Consultant for: Actelion°, V. Gressin Employee of: Actelion°, A. Bérezné: None Declared, E. Chatelus: None Declared, A. Khau Van Kien: None Declared, I. Quéré: None Declared, J. Sibilia: None Declared, E. Hachulla Grant/Research support from: Actelion°, Consultant for: Actelion°, Speakers Bureau: Actelion°