Efficacy of Nintedanib in Idiopathic Pulmonary Fibrosis across Prespecified Subgroups in INPULSIS

Rationale: In the two replicate, placebo-controlled, 52-week, phase III INPULSIS trials, nintedanib 150 mg twice daily significantly reduced the annual rate of decline in FVC, the primary endpoint, in subjects with idiopathic pulmonary fibrosis (IPF). It is unknown if this effect was uniform across all subjects treated with nintedanib. Objectives: To investigate the potential association of demographic and clinical variables with the effect of nintedanib in subjects with IPF. Methods: Subgroup analyses of pooled data from the INPULSIS trials were prespecified. Subgroups were analyzed by sex, age (<65, >= 65 yr), race (white, Asian), baseline FVC percentage predicted (<= 70%, >70%), baseline St. George's Respiratory Questionnaire (SGRQ) total score (<= 40, >40), smoking status (never, ex/current), systemic corticosteroid use (yes/no), and bronchodilator use (yes/no). Measurements and Main Results: A total of 1,061 subjects were treated (nintedanib n = 638, placebo n = 423). There was no statistically significant difference in the effect of nintedanib for the primary endpoint or the key secondary endpoints of change from baseline in SGRQ total score or time to first acute exacerbation in any subgroup. Treatment effects for the key secondary endpoints seemed more pronounced in subjects with baseline FVC <= 70% predicted, because the majority of acute exacerbations and a greater deterioration in SGRQ total score occurred in placebo-treated subjects in this subgroup. Conclusions: Pooled data from the INPULSIS trials support a consistent effect of nintedanib across a range of IPF phenotypes by slowing disease progression across a number of prespecified subgroups.