Efficacy and Safety of Nintedanib in Interstitial Lung Disease Associated with Systemic Autoimmune Rheumatic Diseases: A Systematic Review and Meta-Analysis

Background: Nintedanib, a multi-tyrosine kinase inhibitor, is an approved anti-fibrotic agent for idiopathic pulmonary fibrosis (IPF) and Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD). This study aimed to comprehensively assess the efficacy and safety of nintedanib across the broader spectrum of Systemic Autoimmune Disease-Associated Interstitial Lung Disease (SARD-ILD) patients receiving standard immunosuppressive therapy, focusing primarily on the annual rate of decline in Forced Vital Capacity (FVC). Methods: We conducted a systematic review and meta-analysis of Randomised Controlled Trials (RCTs) and retrospective observational studies investigating the effects of nintedanib on FVC decline and safety outcomes in SARD-ILD patients. A systematic literature search spanning the last 20 years, up to November 2023, was executed across PubMed, Scopus, Embase, and Cochrane Central. Studies were restricted to those published in English. Results: The systematic review included a total of eight RCTs and seven observational studies, comprising 1099 SARD-ILD patients. Of these, two studies provided suitable data for quantitative synthesis (meta-analysis). Pooled results demonstrated a significantly reduced annual rate of FVC decline in the nintedanib arm compared to the placebo arm (MD = 52.49 mL/yr, 95% CI = 18.38–86.59). Conclusion: This systematic review and meta-analysis suggest that nintedanib is associated with a significant reduction in the annual decline of FVC in patients with SARD-ILD who are on standard immunosuppression, highlighting its potential therapeutic benefit and favourable safety profile in this complex patient population.