PRS2 - Systematic Review and Network Meta-Analysis of Approved Medicines for the Treatment of Idiopathic Pulmonary Fibrosis

Abstract

To perform a systematic review and network meta-analysis (NMA) to access the efficacy and tolerability of two of the most recently approved treatments for idiopathic pulmonary fibrosis (IPF), pirfenidone and nintedanib, in adult-patients with IPF. A review was conducted up to September 2017. Randomized controlled trials selection (from CENTRAL, MEDLINE, Embase), data extraction, risk of bias analysis and GRADE assessment were carried out by two authors separately. Direct estimates were calculated using standard pairwise meta-analysis. A Bayesian mixed treatment comparison approach, for NMA estimates with 95% credible intervals, was used to compare pirfenidone and nintedanib. Odds ratios (OR) and number needed to treat for an additional beneficial outcome (NNTB) or an additional negative outcome (NNTH) were also calculated. 10 randomized controlled trials were included. Both drugs showed a positive effect on percentage of FVC decline ≥10% (pirfenidone OR 0.54 (95% CI 0.37-0.80), NNTB 9 (95% CI 7-22); nintedanib OR 0.59 (95% CI 0.41-0.84), NNTB 9 (95% CI 6-23) both with moderate risk of bias). The network meta-analysis did not show any differences when comparing pirfenidone and nintedanib regarding FVC decline (OR 0.91 (95% CrI 0.45-2.03) with low quality of the indirect estimate) or dropouts (OR 0.75 (95% CrI 0.33-1.27) with low quality of the indirect estimate). Nintedanib showed an effect on dropouts OR 1.61 (1.13-2.28) and NNTH 14 (8 - 61) with low quality of the risk of bias assessment. Additionally, there were no differences when comparing the two treatments either to placebo or to each other with respect to acute exacerbations, mortality and serious adverse events. Based on RCTs of 12 month duration in patients with IPF, positive effects were noticed on FVC decline for both treatments and on dropouts for nintedanib. No significant differences were noted between the two treatments regarding any of the outcomes.