RT Journal Article
SR Electronic
T1 Bosentan does not improve outcome in patients with steroid-resistant pulmonary sarcoidosis – Results from a double-blind placebo-controlled phase 2 trial
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P466
VO 44
IS Suppl 58
A1 Katrin Hostettler
A1 Florent Baty
A1 Rebekka Kleiner
A1 Lilian Junker
A1 Michael Tamm
A1 Martin Brutsche
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P466.abstract
AB Background: Sarcoidosis is a disorder of unknown etiology. Most patients improve under corticosteroid treatment, but side-effects and steroid-resistance underline the need for alternative treatments. Endothelin has fibrogenic activity, and the endothelin-system is activated in sarcoidosis. We studied the efficacy and safety of the endothelin receptor antagonist bosentan in sarcoidosis patients. Methods: In a prospective 12-month, double-blind, 1:1-randomized, placebo-controlled phase 2 trial, we assessed the effect of bosentan in patients with steroid-resistant sarcoidosis with impaired exercise capacity and/or resting lung function. Primary endpoints were safety and overall response rate of total lung capacity (TLC), diffusion capacity (DLCO), peak oxygen uptake (VO2peak), 6-minute walking distance (6MWD), and computed tomography (CT)-score. Secondary endpoints included adverse events and quality of life. Results: Twenty patients were randomized. Three patients discontinued the study medication prematurely. No serious drug-related adverse events occurred. At 12 months no statistically significant differences were observed in the primary endpoints including TLC, DLCO, 6MWD, VO2 peak, and CT-score. Sixty-three percent of the patients treated with bosentan showed an increase of 10% in at least one of the primary endpoints, compared to 67% in the placebo group (p=1). Conclusions: There is no evidence to support efficacy of bosentan as an antifibrotic treatment for patients with steroid-resistant pulmonary sarcoidosis. Bosentan was well tolerated and no drug-related adverse effects were observed within the study population.