Efficacy of ambrisentan in the treatment of digital ulcers in patients with systemic sclerosis: a preliminary study.

5 Cader MZ, Filer A, Hazlehurst J et al. Performance of the 2010 ACR/EULAR criteria for rheumatoid arthritis: comparison with 1987 ACR criteria in a very early syno-vitis cohort. Efficacy of ambrisentan in the treatment of digital ulcers in patients with systemic sclerosis: a preliminary study SIR, SSc is characterized by fibrotic thickening of the skin and internal organs and widespread vascular damage [1]. The first vascular event is RP and digital ulcers (DUs) are frequently occurring in SSc evolving to fingertip necrosis, gangrene and amputation with high impact on quality of life [2]. An important pathogenic role is played by endothelin, a molecule with a potent vasoconstrictor agent which is elevated in SSc [3]. The endothelin receptor antagonists have given significant results in the therapy of pulmonary arterial hypertension (PAH), while the only randomized clinical trial in the treatment of DUs is limited to bosentan [4, 5]. In our study, we evaluated the efficacy and tolerability of ambrisentan in the treatment of DUs in patients who failed bosentan. The study and the off-label use of this drug has been approved by the hospital ethics committee (comitato etico interaziendale A. and by the hospital pharmaceutical commission after submission of documentation supporting the treatment. All patients were given a detailed explanation of the study and informed consent was obtained. Six patients, aged between 40 and 68 years (mean age 53.7 AE 11.3 years), with SSc according to ACR Criteria [6], presenting DUs with an onset of between 6 and 9 months were consecutively recruited. Four of the six patients had limited ACA-positive SSc and two of them had SCL-70 antibody-positive diffuse SSc. The mean duration of SSc was 7.1 years with an average duration of onset of RP of 12.3 years. None of the six patients was suffering from PAH. These patients had been treated with ACE inhibitors, prostanoids and bosentan (at least for 6 months) suspended due to unsatisfactory results or side effects. The recruited patients continued to receive i.v. therapy with prostanoids. After 1 month of wash-out after bosentan therapy, patients were treated with ambrisentan. The recruitment period and analysis of the study were conducted between September 2011 and May 2012. Ambrisentan was administered at 5 mg/day and safety follow-up was performed every 4 weeks for 6 months. Each patient was given a diary to report at each visit as follows: date of onset and duration of RP, Raynaud's …