MUSIC: Efficacy and safety of macitentan in idiopathic pulmonary fibrosis (IPF)

Endothelin-1 may contribute to IPF pathophysiology. The prospective double-blind Macitentan USe in an IPF Clinical (MUSIC) trial (NCT00903331) investigated the endothelin receptor antagonist macitentan in adults with IPF of Mean (range) exposure to macitentan was 14.3 (0.0–24.6) months and to placebo was 15.4 (6.3–24.3) months. Median (95% confidence limit) change in FVC was −0.20 L (−0.29 to −0.16) for macitentan and −0.20 L (−0.28 to −0.13) for placebo; ie. no treatment effect on FVC was observed. No difference in time to IPF worsening or death was observed. Adverse events in ≥10% of macitentan-treated patients with a ≥5% difference versus placebo comprised peripheral oedema, anaemia (both favoured placebo), cough (favoured macitentan). Hepatic aminotransferase elevations >3× upper limit of normal occurred in 3.4% of macitentan recipients and 5.1% of placebo recipients. In summary, the primary objective was not met. Long-term macitentan exposure was well tolerated with rates of elevated hepatic aminotransferases comparable to placebo.