Safety and Efficacy of Nerandomilast in Patients With Pulmonary Fibrosis: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

TL;DR

Nerandomilast may help slow lung function decline in pulmonary fibrosis patients without causing additional safety risks.

Contribution

This study provides a meta-analysis of RCTs showing nerandomilast's potential to slow pulmonary fibrosis progression and reduce mortality risk.

Findings

Nerandomilast significantly slowed the decline in forced vital capacity (FVC) compared to placebo.

The drug was associated with a lower pooled risk of all-cause mortality without increasing adverse events.

No improvement in diffusing capacity for carbon monoxide (DLCO) was observed.

Abstract

Nerandomilast, an oral phosphodiesterase‐4 (PDE4) inhibitor, has shown potential in slowing the progression of pulmonary fibrosis. This meta‐analysis evaluated the efficacy and safety of nerandomilast in preserving lung function among patients with pulmonary fibrosis.

MEDLINE, Embase, the Cochrane Library, and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) comparing nerandomilast with placebo. Study quality was assessed using the Cochrane Risk of Bias 2.0 tool. Analyses were performed in RevMan 5.4 using random‐effects models with risk ratios (RR) and mean differences (MD) as effect measures.

Four RCTs (n = 2515) were included. Nerandomilast significantly attenuated the decline in forced vital capacity (FVC) compared with placebo (MD: 69.25 mL, 95% CI: 52.1–86.29), but did not improve diffusing capacity for carbon monoxide (DLCO) (MD: 0.84, 95% CI: −0.56 to 2.24). It was associated with a lower pooled risk of all‐cause mortality (RR: 0.68, 95% CI: 0.52–0.88) without increasing adverse events (RR: 1.00, 95% CI: 0.98–1.02) or serious adverse events (RR: 0.93, 95% CI: 0.76–1.14).

Nerandomilast appears to slow lung function decline in pulmonary fibrosis without added safety risks. Although a lower pooled risk of mortality was observed, individual trials were not powered for mortality outcomes, and event rates were low; therefore, this finding should be interpreted cautiously. Given the heterogeneity of pulmonary fibrosis phenotypes and trial designs, further large‐scale RCTs should explore standardized outcomes, subgroup effects, and combination strategies with nintedanib or pirfenidone.

Nerandomilast appears to slow lung function decline and reduce mortality in pulmonary fibrosis without added safety risks. It may represent a valuable adjunct to existing antifibrotics or a standalone therapy for patients intolerant to standard treatment.

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