SESSION TITLE: Diffuse Lung Disease Poster Discussions
SESSION TYPE: Original Investigation Poster Discussion
PRESENTED ON: Wednesday, October 28, 2015 at 02:45 PM - 04:00 PM
PURPOSE: Purpose: The two replicate, 52-week, randomized, placebo-controlled, Phase III INPULSIS® trials investigated the efficacy and safety of nintedanib 150 mg twice daily (bid) in patients with IPF. In both trials, nintedanib significantly reduced the annual rate of decline in forced vital capacity (FVC), the primary endpoint, compared with placebo. Time to first investigator-reported acute exacerbation and St George’s Respiratory Questionnaire (SGRQ) score change over 52 weeks were key secondary endpoints. Safety was assessed by recording of adverse events. We investigated the efficacy and safety of nintedanib in US patients.
METHODS: Methods: A post-hoc subgroup analysis of patients from US versus non-US sites was conducted for the annual rate of decline in FVC, time to first acute exacerbation and SGRQ change using pooled data from both INPULSIS® trials.
RESULTS: Results: In total, 160 patients (nintedanib 98, placebo 62) were from US sites and 901 (nintedanib 540, placebo 361) were from non-US sites. The adjusted annual rate of decline in FVC in US patients was −94.7 mL/year with nintedanib and −242.5 mL/year with placebo (difference of 147.8 mL/year [95% CI: 56.1, 239.4]) while in non-US patients it was −117.0 mL/year with nintedanib and −220.0 mL/year with placebo (difference of 103.0 mL/year [95% CI: 66.2, 139.7]). The hazard ratio for time to first acute exacerbation was 0.37 (95% CI: 0.06, 2.12) in US patients and 0.68 (95% CI: 0.41, 1.15) in non-US patients, both in favor of nintedanib. The difference between nintedanib and placebo groups in adjusted mean SGRQ score change from baseline was −6.83, 95% CI −10.56, −3.10 for US patients, and −0.43, 95% CI −2.28, 1.42 for non-US patients. Treatment-by-subgroup interactions were not statistically significant for annual rate of FVC decline (p=0.6243), time to first acute exacerbation (p=0.4467) or change from baseline in SGRQ total score (p=0.0792). Adverse events were reported in 100% and 98.4% of US patients, and 94.6% and 88.1% of non-US patients in the nintedanib and placebo groups, respectively.
CONCLUSIONS: Conclusion: Pooled data from the INPULSIS® trials suggest that the effect of nintedanib on annual rate of decline in FVC, time to first acute exacerbation and was similar in US and non-US patients. The effect on SGRQ was numerically larger in the US subpopulation.
CLINICAL IMPLICATIONS: Clinical implications: These findings support the consistent effect of nintedanib on slowing disease progression in patients with IPF.
DISCLOSURE: John Huggins: Grant monies (from industry related sources): John Huggins was a site-PI for the INPULSIS trials. The INPULSIS trials were funded by Boehringer Ingelheim. Mitchell Kaye: Consultant fee, speaker bureau, advisory committee, etc.: Mitchell Kaye has been paid consultancy fees (advisory board) by Boehringer Ingelheim. Zelie Bailes: Employee: Zelie Bailes is an employee of Boehringer Ingelheim. Dirk Esser: Employee: Dirk Esser is an employee of Boehringer Ingelheim. Craig Conoscenti: Employee: Craig Conoscenti is an employee of Boehringer Ingelheim. Kevin Flaherty: Consultant fee, speaker bureau, advisory committee, etc.: Kevin Flaherty has received consultancy fees and fees for lectures as well as fees for participation in review activities and travel reimbursement from Boehringer Ingelheim.
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