Nintedanib in Progressive Pulmonary Fibrosis: A Systematic Review and Meta-Analysis

Medicom Conference Report ATS 2022

“…In addition, the committee made a conditional recommendation to use nintedanib for the treatment of PPF in patients with fibrotic ILD (other than IPF) who failed on standard management but emphasised that research is needed to establish the performance of nintedanib in specific ILDs that display PPF. This recommendation was based on a systematic review that demonstrated significant efficacy of nintedanib in patients with PPF, measured as the annual decline of forced vital capacity (FVC), without persistent adverse events if the therapy was discontinued [7].…”

Analyses of the Efficacy and Safety of Antifibrotic Therapies in Non-IPF Pulmonary Fibrosis, Progressing Despite Management

“…In the recent SENSCIS trial of nintedanib in scleroderma-associated ILD, an apparently unimpressive FVC treatment effect of only 40 mls favoring active treatment led to rapid regulatory approval for nintedanib in that disease because 43% of progression was prevented compared with FVC decline in the placebo arm (93.3 mls) ( 7 ). Thus, it can be argued that “percentage prevention of FVC decline” with active treatment is a helpful metric that might usefully have added context to the efficacy analyses in both current manuscripts ( 1 , 2 ). An average FVC treatment effect of approximately 100 mls covers both smaller treatment effects in patients with less progressive disease and potentially major benefits in patients with rapid disease progression.…”

“…In the this issue of AnnalsATS , readers have been treated to systematic reviews of the efficacy and safety of pirfenidone ( 1 ) (pp. 1030–1039 ) and nintedanib ( 2 ) (pp. 1040–1049 ) in patients with non-IPF pulmonary fibrosis (nIPF) with fibrotic lung diseases progressing despite management.…”

“…This said, there are caveats that merit careful consideration. In analyses of both agents, the authors state comparisons in FVC decline between active and placebo arms, expressed as mean differences in mls/year and, in the case of pirfenidone, mean differences as a percentage of predicted normal values ( 1 , 2 ). At first sight, this appears logical as the decline in FVC, expressed as mls/year, constitutes the primary endpoint in most ILD trials.…”

“…This applies especially to analyses of the INBUILD trial of nintedanib. Ghazipura and colleagues evaluate individual diseases and conclude that treatment effects in attenuating FVC decline were significant in fibrotic connective tissue disease-related ILD, idiopathic fibrotic nonspecific interstitial pneumonia, and fibrotic occupational ILD, but not in fibrotic HP, fibrotic sarcoidosis, or unclassified fibrotic ILD ( 2 ). However, the evaluation of treatment-related mean differences in FVC decline in individual diseases in the INBUILD trial served only to establish that treatment effects are broadly uniform across disease subgroups ( 8 ).…”