Comparative efficacy and safety of monotherapy and combination pharmacotherapies for idiopathic pulmonary fibrosis: a network meta-analysis of randomized controlled trials
Abstract
Background: Idiopathic pulmonary fibrosis (IPF) is a fatal, progressive fibrosing lung disease. While novel agents and combinations are emerging, head-to-head trials are scarce, underscoring the need for robust comparative evidence to guide treatment prioritization.
Methods: We conducted a systematic review and network meta-analysis (NMA) of IPF RCTs in adults, searching PubMed, Embase, Cochrane Library, and Web of Science through 1 December 2025. Eligible studies compared pharmacotherapies (mono/combination) with placebo or active comparators and reported prespecified outcomes. Primary outcomes were forced vital capacity (FVC) change and disease progression; secondary outcomes included all-cause mortality, adverse events (AEs), serious AEs (SAEs), and DLCO change. Risk of bias was assessed via RoB 2, with frequentist random-effects NMA for continuous/binary outcomes and a random-effects model for disease progression. Treatment rankings used SUCRA, and evidence certainty was evaluated via GRADE with CINeMA.
Results: Thirty-five reports (8,983 participants, 21 strategies) were included. RoB 2 ratings were low (19 studies) or raised some concerns (16). For FVC preservation, recombinant human pentraxin-2 (RHP) (SMD = 0.72, 95% CI: 0.23-1.20), rentosertib (SMD = 0.63, 95% CI:0.04-1.22), and nintedanib (SMD = 0.50, 95% CI:0.27-0.73) showed the highest statistical probability of benefit versus placebo, though these rankings are based primarily on low-certainty indirect…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 8,983 participants or records.
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