Effectiveness of antifibrotics on health-related quality of life in patients with interstitial lung disease: a systematic review and meta-analysis.

BACKGROUND: Interstitial lung disease (ILD) leads to progressive lung function decline and significant respiratory symptoms. Although antifibrotic agents preserve lung function and reduce mortality in ILD, their impact on health-related quality of life (HRQoL) remains unclear. OBJECTIVES: We aimed to evaluate whether antifibrotic agents improve HRQoL and their effectiveness in treating HRQoL-related symptoms in patients with ILD. DESIGN: Systematic review and meta-analysis. DATA SOURCES AND METHODS: A literature search was conducted using MEDLINE, EMBASE, and the Cochrane Library from inception to August 25, 2025. The search included terms related to ILD, antifibrotic agents, and measures of HRQoL. HRQoL outcomes were assessed using the St. George's Respiratory Questionnaire (SGRQ), including total and domain scores. Data were pooled using a random-effects model, with outcomes reported as mean differences (MD) or relative risks (RR) and heterogeneity evaluated using the I² statistic. RESULTS: A total of 13 randomized controlled trials were included. Antifibrotic agents showed significant improvement in SGRQ scores, particularly in the symptom (MD: -2.59, 95% confidence interval [CI]: -4.56 to -0.61; I² = 32%) and activity (MD: -2.88, 95% CI: -4.82 to -0.94; I² = 34%) domains. Antifibrotics reduced the rate of cough (RR: 0.77, 95% CI: 0.64-0.94; I² = 0%) and dyspnea (RR: 0.71, 95% CI: 0.56 to 0.89; I² = 0%). However, fatigue was frequently observed in patients treated with antifibrotics (RR: 1.48, 95% CI: 1.20-1.83; I² = 0%) compared with the non-antifibrotic group. Most trials were judged to have low-to-moderate risk of bias, and the certainty of evidence was rated very low for total SGRQ scores but low to moderate for domain-specific outcomes and symptoms. CONCLUSION: Antifibrotic agents may improve HRQoL and reduce dyspnea and cough in patients with ILD, but the certainty of evidence is low, and they may increase fatigue, requiring careful monitoring.Trial registration:The study protocol was registered in PROSPERO (CRD42023450917).