Background Patients with Systemic Autoimmune Diseases (SADs), in particular, systemic sclerosis, are prone to suffer from severe Raynaud's phenomenon (RP), accompanied with digital ulcers secondary to ischemia and associated with a high rate of morbidity and mortality. Bosentan, a dual endothelin receptor antagonist, is a therapeutic option for refractory cases with an inadequate response to conventional management.

Objectives The objectives of our study were: i) to assess safety and efficacy of bosentan in patients suffering from different kinds of SADs and active digital ulcers secondary to RP, ii) to determine predictive factors of response, and iii) to identify predictive factors for survival.

Methods This is a retrospective observational study of patients suffering from SADs and digital ulcers secondary to RP, treated with bosentan in our department between January 1st, 2005 and December 31st, 2014. Patients with ischemic ulcers caused by other factors were excluded. The following baseline independent variables were considered: type of SAD, exposition to cold or to toxic substances, clinical and epidemiological characteristics, concomitant treatments, the coexistence of pulmonary hypertension, and number and location of digital ulcers. Therapeutic response, adverse effects, the need for amputation and death were considered as dependent outcome variables. Chi-square, Student t test, and Mann-Whitney U test were used to establish statistical significance in the univariate analysis between independent baseline variables and outcomes. A p<0.05 was considered significant.

Results We included 31 patients (26 women, mean age 57 years). Twenty patients had systemic sclerosis (10 cases the limited form, and 10 cases the diffuse form). Eight patients had concomitant pulmonary hypertension. Mean follow-up after starting bosentan was 1470 days. Six patients had, at least, an adverse effect, being the most frequent alterations of liver function tests. In 87% of the cases, ulcers improved significantly, with a clinical response within the first 12 weeks of treatment in 77% of the cases. Ninety percent of the patients received concomitant treatment with calcium channel blockers and 45% had received previous treatment with prostaglandins. Despite bosentan therapy, amputation was done in 4 patients. Type of SAD, gender, or exposition to cold did not show any significant correlation with morbidity and mortality. Nine patients died. Smoking habit showed a correlation with death (p=0.05). There was a significant correlation between the duration of the disease and death (p=0.0235), as well as with the age of the patient (p=0.0013). Pulmonary hypertension was predictive of a poor therapeutic response (p=0.043) and mortality (p=0.015).

Conclusions This open study suggests that bosentan is an effective agent for ischemic digital ulcers in patients with SADs, with a favorable safety profile. Age and associated pulmonary hypertension are predictors of mortality and poor outcome.

Disclosure of Interest None declared