Abstract
This study compares their safety profiles using real-world pharmacovigilance data and meta-analysis to guide clinical use. The gastrointestinal disorders and skin-related ADRs listed in the latest instructions for pirfenidone and nintedanib were systematically reviewed and subsequently analyzed using the FDA Adverse Event Reporting System (FAERS) database. Adverse drug event (ADE) reports for pirfenidone (2014-Q1 2025) and nintedanib (2014-Q1 2025) were extracted from the FAERS database via OpenVigil 2.1. ADE signals were analyzed using MedDRA's system organ class (SOC) and preferred terms (PT), with reporting odds ratio (ROR) for signal detection. Randomized controlled trials (RCTs) were retrieved from Cochrane, PubMed, Embase, and ClinicalTrials.gov, and meta-analysis was performed using RevMan 5.3. Pirfenidone and nintedanib were associated with 26,352 and 9,809 ADE reports, respectively, primarily in patients aged ≥ 65. Gastrointestinal disorders were common for both, but nintedanib showed fewer skin-related ADRs. Gender-based differences were observed: nintedanib's gastrointestinal ADRs varied by gender, while pirfenidone's skin-related ADRs differed significantly. Most reports originated from the U.S. Meta-analysis of 10 RCTs (6 pirfenidone, 4 nintedanib) showed both drugs slowed forced vital capacity (FVC) decline and reduced respiratory-related mortality. Nintedanib demonstrated superior efficacy in reducing acute exacerbations (RR = 0.57, 95%CI [0.34-0.98], I2 = 47%). Both drugs primarily caused gastrointestinal ADRs (e.g., nausea, vomiting), with pirfenidone linked to more photosensitivity reactions. Integrated pharmacovigilance and RCT analyses highlight the safety profiles of pirfenidone and nintedanib, offering evidence for clinical decision-making in idiopathic pulmonary fibrosis (IPF) treatment.