Systematic Review and Meta-analysis of Pirfenidone, Nintedanib, and Pamrevlumab for the Treatment of Idiopathic Pulmonary Fibrosis

Abstract

Background: The comparative efficacy of pirfenidone, nintedanib, and pamrevlumab in slowing the rate of forced vital capacity (FVC) decline and mortality in patients with idiopathic pulmonary fibrosis (IPF) is unknown. Objective: To perform a systematic review and meta-analysis (MA) of these drugs for IPF. Methods: We searched CENTRAL, PubMed, EMBASE, ClincalTrials.gov, and the World Health Organization’s registry databases up to March 2020. Phase II/III randomized controlled trials in adults with IPF were eligible. The random-effect model was implemented calculating the effect size and respective 95% CI as Cohen’s d for change from baseline FVC (in percentage predicted and liters) and odds ratio (OR) for 10% reduction in FVC and all-cause mortality (ACM). Results: Six studies were included in the MA. For change from baseline in percentage predicted FVC, the MA indicated that the 3 drugs were more effective than placebo (pirfenidone: d=3.30%, 95% CI=2.15-4.45; nintedanib: d=3.15%, 95% CI=2.35-3.95; pamrevlumab: d=4.30%, 95% CI=0.45-8.15). These results are superimposable to those relating to change from baseline FVC in liters (pirfenidone: d=0.09L, 95% CI=0.04-0.14; nintedanib: d=0.13L, 95% CI=0.10-0.16; pamrevlumab: d=0.20L, 95% CI=0.05-0.35). Each drug had a positive effect on 10% reduction in FVC (pirfenidone: OR=0.57, 95% CI=0.45-0.74; nintedanib: OR=0.66, 95% CI=0.51-0.85; pamrevlumab: OR=0.24, 95% CI=0.08-0.73), but only pirfenidone showed an effect on ACM (OR=0.50; 95% CI=0.31-0.83). Conclusion and Relevance: This MA provided encouraging results on pamrevlumab efficacy in slowing the decline in FVC compared with pirfenidone and nintedanib. Actually, in phase 3, it could become a potential IPF treatment.

The safety of nintedanib for the treatment of interstitial lung disease: A systematic review and meta-analysis of randomized controlled trials

“…Previous studies have suggested that nintedanib could reduce the decline in forced vital capacity (FVC), preserve quality of life, lower the incidence of acute exacerbations, and increase survival time in patients with IPF [6][7][8]. In previous network meta-analysis of randomized controlled trials (RCTs) comparing 11 treatments in IPF, nintedanib was 1 of 4 medications had benefit, including in pulmonary function decline, exacerbation and mortality [9][10][11][12][13]. More recent studies have shown that nintedanib can also reduce the decline in FVC in patients with systemic sclerosis (SSc)-associated ILD and progressive fibrosis ILD (PF-ILD) in addition to those with IPF [14,15].…”

The Impact of Inflammatory Immune Reactions of the Vascular Niche on Organ Fibrosis

“…The main representative drugs are farnesoid X receptor (FXR) agonists, TGF-β antagonists and Pirfenidone. Among them, nintedanib and pirfenidone, as representative drugs for the treatment of IPF, can slow down the rate of decline of lung function in IPF, and have some effect in reducing the risk of IPF mortality and acute exacerbations, while pamrevlumab has a relatively better effect in reducing the decline of lung function compared with pirfenidone and nintedanib (Di Martino et al, 2021;Petnak et al, 2021). Thus developing more effective antifibrosis drugs or early intervention drugs remains a research hotspot (Ren et al, 2020).…”

Treatment of Idiopathic Pulmonary Fibrosis

“…Studies have shown that it has a good safety profile, and it slows the decline in FVC compared with pirfenidone and nintedanib. It may become a potential IPF treatment [ 67 ]. Further larger trials are needed.…”