No Effect of Dose Adjustments on Long-Term Reduction in FVC Decline With Nintedanib in Patients With Idiopathic Pulmonary Fibrosis (IPF)

Abstract

SESSION TITLE: Diffuse Lung Disease 2 SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: In the two Phase III INPULSIS trials, nintedanib reduced disease progression by significantly reducing the annual rate of decline in forced vital capacity (FVC) in patients with IPF. Patients who completed the 52-week treatment period and follow-up visit in an INPULSIS trial could receive open-label nintedanib in an extension trial (INPULSIS-ON). Patients treated with placebo in INPULSIS initiated nintedanib in INPULSIS-ON; patients treated with nintedanib in INPULSIS continued nintedanib in INPULSIS-ON. Dose reductions to 100 mg bid and treatment interruptions were allowed to manage adverse events; re-escalation to 150 mg bid was permitted. We investigated whether dose adjustment influenced the effect of nintedanib on long-term decline in FVC in INPULSIS-ON. METHODS: The annual rate of decline in FVC over 96 weeks in INPULSIS-ON was assessed in subgroups of patients by whether they had ≥1 dose reduction and interruption, ≥1 dose reduction only, ≥1 treatment interruption only, or no dose reduction or treatment interruption, and by dose intensity ≤90% versus >90%. Dose intensity was defined as the amount of drug administered over the trial divided by the amount of drug that would have been received had the 150 mg bid dose been administered throughout the trial. All available FVC measurements between baseline and week 96 of INPULSIS-ON were used to calculate the slope of FVC decline. Analyses were descriptive and based on a data snapshot in October 2015. RESULTS: Of 807 patients who completed the INPULSIS trials, 734 patients (91%) participated in INPULSIS-ON. The adjusted annual rate (SE) of decline in FVC over 96 weeks in all patients in INPULSIS-ON was −117.8 (6.8) mL/year, which was of a similar magnitude to the adjusted annual rate (SE) of decline in FVC over 52 weeks in patients treated with nintedanib in INPULSIS (−113.6 [11.0] mL/year). Approximately half (53.7%) of patients did not have a dose reduction or treatment interruption during INPULSIS-ON. The adjusted annual rates (SE) of decline in FVC over 96 weeks in INPULSIS-ON in patients who had ≥1 dose reduction or treatment interruption (n=150), ≥1 dose reduction only (n=94), ≥1 treatment interruption only (n=96), and no dose reduction or treatment interruption (n=394) were −129.9 (14.1) mL/year, −121.4 (19.9) mL/year, −119.5 (15.3) mL/year and −112.0 (10.1) mL/year, respectively. In patients with dose intensity of ≤90% (n=246) and >90% (n=488) in INPULSIS-ON, the adjusted annual rates (SE) of decline in FVC over 96 weeks were −104.9 (16.5) mL/year and −112.2 (12.5) mL/year, respectively. CONCLUSIONS: Results from INPULSIS-ON demonstrated a consistent effect of nintedanib on disease progression, as measured by the annual rate of decline in FVC, in patients with IPF irrespective of whether they had a dose reduction or treatment interruption. CLINICAL IMPLICATIONS: These results suggest that the long-term efficacy of nintedanib in reducing disease progression in patients with IPF is maintained in patients who require dose adjustment to manage adverse events. Primary source of funding: Boehringer Ingelheim. DISCLOSURE: John Huggins: Grant monies (from industry related sources): Boehringer Ingelheim, Roche/Genentech, Kadmon, Consultant fee, speaker bureau, advisory committee, etc.: Consulting/advisory board for Boehringer Ingelheim, Roche/Genentech, Kadmon, Consultant fee, speaker bureau, advisory committee, etc.: Advisory board for iBIOS Wibke Stansen: Employee: Employee of Boehringer Ingelheim Pharma GmbH & Co. KG Manuel Quaresma: Employee: Employee of Boehringer Ingelheim Pharma GmbH & Co. KG Michael Kreuter: Grant monies (from industry related sources): Research grants from Boehringer Ingelheim and Roche, Consultant fee, speaker bureau, advisory committee, etc.: Compensations for advisory boards or lectures to himself or his institution from Boehringer Ingelheim and Roche The following authors have nothing to disclose: Keith Meyer No Product/Research Disclosure Information