Nintedanib, Pirfenidone and Pirfenidone Versus Nintedanib: A Systematic Review And Meta-Analysis

Abstract Background: Patients with idiopathic pulmonary fibrosis have a poor overall prognosis. Only nintedanib and pirfenidone have been shown to reduce mortality. Objective: This systematic review and meta-analysis aims to assess the efficacy of nintedanib, pirfenidone, and pirfenidone vs nintedanib on patient important outcomes. Methods: Randomized trials were retrieved from MEDLINE, Cochrane, and EMBASE. The primary outcome was mortality. The secondary outcomes included change in FVC, acute exacerbations and hospitalizations and adverse drug effects leading to discontinuation. We used an inverse variance random effects meta-analysis method to calculate pooled relative risk (RR), standardized mean difference (SMD) and mean difference (MD).Results: A total of 13 studies were included. Both nintedanib [RR 0.63 (0.47,0.85); moderate certainty] and pirfenidone [RR 0.68 (0.47,0.99); moderate certainty] probably reduce all-cause mortality when compared to placebo, but only nintedanib [SMD 0.47 (0.34, 0.60); high certainty] reduces change in FVC. Nintedanib [RR 0.69 (0.48,0.99); moderate certainty],but not pirfenidone probably reduces acute exacerbations or hospitalizations compared to placebo. Compared with placebo, neither nintedanib nor pirfenidone increased risk of drug discontinuation due to adverse effect but there is probably risk of patient drug discontinuation with pirfenidone compared to nintedanib [RR 4.34 (1.72 to 10.98); moderate certainty].Conclusion: Both nintedanib and pirfenidone probably reduce all-cause mortality. Nintedanib is probably more tolerable to pirfenidone in regard to compliance and may be more effective than pirfenidone in reducing mortality rate and in slowing disease progression. Larger head to head randomized trials are needed.