Efficacy and safety of nerandomilast in patients with autoimmune disease-related progressive pulmonary fibrosis in the FIBRONEER-ILD trial.

Abstract

This study aimed to investigate the effects of nerandomilast in patients with autoimmune disease-related interstitial lung diseases (autoimmune ILDs) and progressive pulmonary fibrosis (PPF) in the FIBRONEER-ILD trial. Patients with PPF were randomised to receive nerandomilast 9 mg twice a day, nerandomilast 18 mg twice a day, or placebo. Among patients with autoimmune ILDs, we evaluated the change in forced vital capacity (FVC) at week 52, and time-to-event endpoints and adverse events over the whole trial. Among 325 patients with autoimmune ILDs, adjusted mean (SE) changes in FVC (mL) at week 52 were -107.1 (25.0) in the placebo group, -61.2 (23.3) in the nerandomilast 9 mg twice a day group (difference vs placebo: 45.9 [95% CI: -20.8 to 112.6]), and -64.9 (23.5) in the nerandomilast 18 mg twice a day group (difference vs placebo: 42.2 [-24.9, 109.3]). Over the whole trial (mean exposure to trial medication: 15.8 months), the hazard ratio (HR) vs placebo for time to first acute exacerbation of ILD, hospitalisation for respiratory cause, or death was 0.66 (95% CI: 0.40-1.10) for nerandomilast 9 mg twice a day and 0.56 (0.33-0.94) for nerandomilast 18 mg twice a day, and the HR for time to death was 0.40 (0.17-0.94) for nerandomilast 9 mg twice a day and 0.28 (0.11-0.69) for nerandomilast 18 mg twice a day. Adverse events led to treatment discontinuation in 13.0%, 8.0%, and 10.6% of the placebo, nerandomilast 9 mg twice a day, and nerandomilast 18 mg twice a day groups, respectively. Consistent with the overall trial population, among patients with autoimmune ILDs in FIBRONEER-ILD, nerandomilast slowed progression of pulmonary fibrosis and was well tolerated.