C103-18 Nerandomilast in Fibrosing Interstitial Lung Diseases: A Meta-Analysis Consolidating the Evidence From Randomized Controlled Trials

Rationale Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) are characterized by an irreversible decline in lung function and poor survival despite currently available antifibrotics. Nerandomilast has emerged as a potential therapy targeting both pro-inflammatory and pro-fibrotic pathways. Building on recent randomized controlled trials (RCTs) of nerandomilast in fibrosing interstitial lung diseases (ILDs), we conducted this meta-analysis to consolidate the latest evidence and comprehensively assess its efficacy and safety. Methods We systematically searched MEDLINE, Embase, and Cochrane CENTRAL for RCTs comparing nerandomilast 18 mg with placebo, with or without background antifibrotic therapy, in adults with idiopathic or progressive pulmonary fibrosis. Primary outcomes were changes in forced vital capacity (FVC, mL) and diffusing capacity for carbon monoxide (DLCO, % predicted). Secondary outcomes included all-cause mortality and adverse events. Adjusted mean differences (aMDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model in Review Manager. Results Three RCTs comprising 1,715 patients were included. The mean age was 68.9 years, 70% were male, and 57% received background antifibrotic therapy. Nerandomilast significantly attenuated the decline in FVC compared with placebo (MD: 72.64 mL; 95% CI: 49.79-95.48; p < 0.01). No significant difference was observed in DLCO % predicted (MD: 1.05%; 95% CI: −0.51 to 2.61; p = 0.18). Nerandomilast was associated with a lower risk of all-cause mortality (RR: 0.61; 95% CI: 0.39-0.94; p = 0.03) but a higher incidence of diarrhea (RR: 1.95; 95% CI: 1.29-2.93; p < 0.01). Conclusions Nerandomilast therapy significantly preserves FVC and may reduce mortality in patients with idiopathic and progressive pulmonary fibrosis, albeit with an increased risk of diarrhea. These findings consolidate current evidence supporting nerandomilast as a promising antifibrotic agent and underscore the need for long-term phase IV studies to define its role in the evolving management of fibrosing ILDs. This abstract is funded by: none