Consistent Effect of Nintedanib on Reducing FVC Decline in Patients With or Without Honeycombing in the INPULSIS Trials of Idiopathic Pulmonary Fibrosis

SESSION TITLE: Diagnosis and Treatment of IPF SESSION TYPE: Original Investigation Slide PRESENTED ON: Monday, October 26, 2015 at 01:30 PM - 02:30 PM PURPOSE: The Phase III INPULSIS® trials assessed the efficacy and safety of nintedanib 150 mg twice daily (bid) versus placebo in patients with idiopathic pulmonary fibrosis (IPF). To be eligible for inclusion, a patient had to have a chest high-resolution computed tomography (HRCT) scan showing honeycombing and/or a combination of reticular abnormality and traction bronchiectasis, without nodules or consolidation or features suggestive of alternative causes. Nintedanib significantly reduced the annual rate of decline in forced vital capacity (FVC), the primary endpoint, in both trials. Key secondary endpoints were time to first acute exacerbation and change from baseline in St George's Respiratory Questionnaire total score, both over 52 weeks. In this subgroup analysis, we investigated whether the treatment effect of nintedanib was the same in patients with or without honeycombing on HRCT at baseline. METHODS: A post-hoc subgroup analysis of patients with or without honeycombing on HRCT at baseline was undertaken using pooled data from both INPULSIS® trials. RESULTS: 567 patients (nintedanib 326, placebo 241) had honeycombing at baseline and 494 (nintedanib 312, placebo 182) did not. Baseline characteristics for patients with versus without honeycombing were: mean age 67.4 versus 66.0 years, 81.5% versus 76.7% were male, mean FVC % predicted was 79.9% versus 79.1%, mean DLco % predicted was 44.8% versus 50.0%. In patients with honeycombing, the adjusted annual rate of decline in FVC was −117.8 mL/year with nintedanib and −212.8 mL/year with placebo (difference: 95.0 mL/year [95% CI: 49.0, 141.0]). In patients without honeycombing, the adjusted annual rate of decline in FVC was −109.3 mL/year with nintedanib and −237.2 mL/year with placebo (difference: 127.9 mL/year [95% CI: 76.8, 179.1]). The treatment-by-subgroup interaction for the primary endpoint was not significant (p=0.6177), indicating that the effect of nintedanib was similar between the subgroups. No significant treatment-by-subgroup interaction was observed for either key secondary endpoint. CONCLUSIONS: In the INPULSIS® trials, the rate of FVC decline in the placebo groups was similar in patients with or without honeycombing on baseline HRCT. Nintedanib slowed disease progression by reducing the annual rate of FVC decline by a similar magnitude in patients with or without honeycombing on HRCT. CLINICAL IMPLICATIONS: Nintedanib has a consistent effect on slowing disease progression in patients with IPF irrespective of the presence of honeycombing on HRCT. DISCLOSURE: Amy Case: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim, Consultant fee, speaker bureau, advisory committee, etc.: Intermune / Genentech Jorge Capapey: Employee: Boehringer Ingelheim Pharma GmbH & Co. KG Toshio Kimura: Employee: Boehringer Ingelheim Pharma GmbH & Co. KG Ganesh Raghu: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim No Product/Research Disclosure Information