A pilot study into bosentan (Tracleer®) as an immunomodulating agent in patients with Behçet’s disease
Tim B. van der Houwen,1,2 P. Martin van Hagen,1,2 Jasper. H. Kappen,3 Robert W.A.M. Kuijpers,4 Paul L.A. van Daele,1,2 Wim A. van Dik,1 Jan A.M. van Laar1,2
1 Department of Immunology, Section Clinical Immunology, Erasmus University Medical Center, Rotterdam, Rotterdam, the Netherlands
2 Department of Internal Medicine, Section Clinical Immunology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
3 Allergy and Clinical Immunology, Immunomodulation and Tolerance Group, National Heart and Lung Institute, Inflammation Repair and Development, Imperial College, London, United Kingdom; Department of Pulmonology, STZ Centre of Excellence for Asthma & COPD, Franciscus group, Rotterdam, United Kingdom
4 Department of Ophthalmology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
Abstract
Background: Behçet’s disease (BD) is an auto-inflammatory vasculitis characterized by aphthous oro-genital ulcers, inflammatory skin changes and uveitis. Treatment is mainly immunosuppressive. Interestingly, elevated endotheline-1 (ET-1) levels suggest a possible beneficial effect of treatment with an ET-1 receptor antagonist.
Objectives: The aim of our study was to investigate the possible beneficial effect of the ET-1 inhibitor bosentan.
Methods: We performed a prospective double-blind placebo controlled pilot study into the effect and safety of bosentan in BD patients. Disease activity was measured using the Behçet Disease Current Activity Form. The primary objective of the study was to determine whether bosentan is therapeutically effective in patients with BD. Secondary endpoints were safety, tapering of medication and the effect of bosentan on possible disease activity markers such as ET-1, circulating endothelial cells (CECs), soluble interleukin-2 receptor (sIL2R) and cytokine levels.
Results: Ten patients were randomized to either bosentan or placebo. Overall, no effect on disease activity was observed, although one patient responded clinically and continued treatment after the study period. Despite one SAE, bosentan seems safe to use. No effect on tapering of medication, CECs, sIL2R and cytokine levels was found. In the bosentan group, ET-1 levels were elevated during the treatment period, with no correlation with disease activity.
Conclusions: Although this is a small pilot study, bosentan appears to be safe in BD patients. One patient had a durable and significant clinical response. Our observations should be confirmed and extended in a larger patient cohort to be of significant impact in the treatment options for BD.
Key words: Behçet’s disease, bosentan, BDCAF, treatment, trial,