Background: In the INBUILD trial in patients with chronic fibrosing interstitial lung diseases (ILDs) and a progressive phenotype, nintedanib reduced the rate of ILD progression with adverse events that were manageable for most patients. We investigated the potential impact of immunomodulatory therapies on the efficacy and safety of nintedanib. Methods: Subjects with fibrosing ILDs other than idiopathic pulmonary fibrosis, who had shown progression of ILD within the prior 24 months despite management in clinical practice, were randomized to receive nintedanib or placebo. Certain immunomodulatory therapies were restricted for the first 6 months. We analyzed post-hoc the rate of decline in forced vital capacity (FVC) over 52 weeks in subgroups by glucocorticoid use at baseline and in analyses excluding subjects or FVC measurements taken after initiation of restricted immunomodulatory or antifibrotic therapies. Results: Of 663 subjects, 361 (54.4%) were taking glucocorticoids at baseline (353 at a dose of ≤ 20 mg/day). In the placebo group, the adjusted rate of decline in FVC (mL/year) over 52 weeks was numerically greater in subjects taking than not taking glucocorticoids at baseline (− 206.4 [SE 20.2] vs − 165.8 [21.9]). The difference between the nintedanib and placebo groups was 133.3 (95% CI 76.6, 190.0) mL/year in subjects taking glucocorticoids at baseline and 76.1 (15.0, 137.2) mL/year in subjects who were not (interaction P = 0.18). The effect of nintedanib on reducing the rate of FVC decline in analyses excluding subjects or measurements taken after initiation of restricted immunomodulatory or antifibrotic therapies was similar to the primary analysis. The adverse event profile of nintedanib was similar between subjects who did and did not use prohibited or restricted therapies at baseline or during treatment with trial drug. Conclusions: In patients with progressive fibrosing ILDs, the effect of nintedanib on reducing FVC decline was not influenced by the use of immunomodulatory therapies. Nintedanib can be used in combination with immunomodulatory therapies in patients with progressive fibrosing ILDs. Trial registration ClinicalTrials.gov, NCT02999178. Registered 21 December 2016, https://clinicaltrials.gov/ct2/show/NCT02999178
Bibliographical noteFunding Information:
VC reports research grants, personal fees, and non-financial support from Boehringer Ingelheim; personal fees from AstraZeneca, Bayer, Merck Sharp & Dohme, Celgene, FibroGen, Galapagos, Galecto, Novartis, Sanofi, and Shionogi; and personal fees and non-financial support from Actelion, and Roche/Promedior. LR reports personal fees from Asahi Kasei, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, CSL Behring, FibroGen, ImmuneWorks, Nitto, Pliant Therapeutics, Promedior, Respivant, Roche, and Toray. IR reports personal fees from Boehringer Ingelheim and Genentech/Roche and grants from Genentech/Roche. MO reports personal fees from Boehringer Ingelheim and Bristol-Myers Squibb. JWS has nothing to disclose. ST reports personal fees from Boehringer Ingelheim and Roche and grants from Roche. MW reports grants paid to her institution from Boehringer Ingelheim and Hoffman-La Roche and fees paid to her institution from Boehringer Ingelheim, Hoffman-La Roche, Galapagos, Respivant, Novartis, and Savara. MS is an employee of mainanalytics GmbH, which was contracted by Boehringer Ingelheim to conduct analyses presented in this manuscript. CC, SSt, and RSH are employees of Boehringer Ingelheim. MK reports personal fees from AstraZeneca, Boehringer Ingelheim, Covance, Galapagos, Gilead, GlaxoSmithKline, Indalo, Prometic, Roche, and Third Pole, Inc and grants from Boehringer Ingelheim, Gilead, GlaxoSmithKline, Prometic, and Roche.
We thank the patients who participated in the INBUILD trial. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). The authors did not receive payment for development of this manuscript. Writing assistance was provided by Elizabeth Ng, B.Sc and Wendy Morris, M.Sc of FleishmanHillard, London, UK, which was contracted and funded by Boehringer Ingelheim. Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.
The INBUILD trial was funded by Boehringer Ingelheim.
© 2021, The Author(s).