OP0115 EFFECT OF NINTEDANIB ON PROGRESSION OF INTERSTITIAL LUNG DISEASE (ILD) IN PATIENTS WITH AUTOIMMUNE DISEASE-RELATED ILDS: FURTHER DATA FROM THE INBUILD TRIAL

Abstract

Background:In the INBUILD trial in patients with progressive fibrosing ILDs, nintedanib reduced the rate of decline in forced vital capacity (FVC) versus placebo over 52 weeks both in the overall population and in the subgroup with autoimmune disease-related ILDs. Patients continued blinded randomised treatment until the end of the trial.Objectives:Assess the effects of nintedanib on the risks of death, acute exacerbation of ILD or death, and disease progression or death over the whole INBUILD trial in patients with autoimmune disease-related ILDs and a progressive phenotype.Methods:Patients with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF) were randomised to receive nintedanib 150 mg bid or placebo. Time to i) death, ii) first acute exacerbation of ILD or death, and iii) disease progression (absolute decline in FVC ≥10% predicted) or death, over the whole trial were analysed in patients with autoimmune disease-related ILDs. Incidence rates of adverse events per 100 patient–years were calculated based on events with onset between the first trial drug intake and the last intake plus 28 days. Analyses were descriptive.Results:Of 663 patients, 170 (82 nintedanib, 88 placebo) had autoimmune disease-related ILDs (89 RA-ILD, 39 SSc-ILD, 19 MCTD-ILD, 23 other autoimmune ILDs including Sjogren’s disease-related ILD [n=7], interstitial pneumonia with autoimmune features [n=5] and undifferentiated CTD-ILD [n=3]). Over the whole trial, in the nintedanib and placebo groups, respectively, mean (SD) exposure to drug was 15.4 (7.4) and 16.9 (6.1) months and maximum exposure was 26.0 and 25.2 months; 62 (75.6%) and 68 (77.3%) patients in these groups, respectively, completed the planned observation time. Over the whole trial, in the nintedanib and placebo groups, respectively, 9.8% and 12.5% of patients died, 12.2% and 20.5% of patients had ≥1 acute exacerbation of ILD or died, and 40.2% and 53.4% of patients had disease progression or died (Table). Diarrhoea was the most common adverse event, with incidence rates of 139.2 and 26.3 events per 100 patient–years in the nintedanib and placebo groups, respectively. Adverse events led to treatment discontinuation in 20.7% of patients in the nintedanib group and 13.6% of patients in the placebo group.Conclusion:Data from the INBUILD trial suggest that nintedanib has a clinically meaningful effect on slowing the progression of ILD in patients with progressive fibrosing autoimmune disease-related ILDs, with adverse events that can be tolerated by most patients.Table.Nintedanib (n=82)Placebo (n=88)HR (95% CI)*Death8 (9.8)11 (12.5)0.80 (0.32, 1.98)≥1 acute exacerbation of ILD or death10 (12.2)18 (20.5)0.58 (0.27, 1.27)Disease progression (absolute decline in FVC ≥10% predicted) or death33 (40.2)47 (53.4)0.72 (0.46, 1.13)n (%) with event over the whole trial (mean [SD] exposure: 15.4 [7.4] and 16.9 [6.1] months in nintedanib and placebo groups, respectively). *Based on time to first event.Disclosure of Interests:Eric Matteson Grant/research support from: Pfizer, Consultant of: Boehringer Ingelheim, Gilead, TympoBio, Arena Pharmaceuticals, Speakers bureau: Simply Speaking, Clive Kelly Consultant of: Boehringer Ingelheim, Speakers bureau: Boehringer Ingelheim, Jörg Distler Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Paid instructor for: Boehringer Ingelheim, Speakers bureau: Boehringer Ingelheim, Anna-Maria Hoffmann-Vold Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Actelion, Bayer, GlaxoSmithKline, Speakers bureau: Boehringer Ingelheim, Actelion, Roche, James Seibold Shareholder of: BriaCell, Pacific Therapeutics, Consultant of: Atlantic, Blade Therapeutics, Eicos Sciences, Eiger Biopharmaceuticals, Indalo Therapeutics, Mitsubishi Tanabe Pharma, Bayer, Xenikos, Boehringer Ingelheim, Camurus, Corbus Pharmaceuticals, EMD Serono, Speakers bureau: Boehringer Ingelheim, Shikha Mittoo Grant/research support from: Pfizer, Consultant of: Novartis, Abbvie, Pfizer, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche, Paul F. Dellaripa Grant/research support from: Paul Dellaripa has received institutional grants from Genentech, Consultant of: Paul Dellaripa participated in advisory boards for Boehringer Ingelheim, Alexandra James Employee of: Employee of Boehringer Ingelheim, Rozsa Schlenker-Herceg Employee of: Employee of Boehringer Ingelheim, Susanne Stowasser Employee of: Employee of Boehringer Ingelheim, Manuel Quaresma Employee of: Employee of Boehringer Ingelheim, Kevin R. Flaherty Grant/research support from: Kevin Flaherty has received grants from Boehringer Ingelheim, Consultant of: Kevin Flaherty has acted as a consultant for Boehringer Ingelheim, Bellerophon, Blade Therapeutics, Roche/Genentech, and VeracyteHe was a member of the INBUILD trial Steering Committee