Long-term treatment of patients with idiopathic pulmonary fibrosis with nintedanib: results from the TOMORROW trial and its open-label extension

Abstract

The TOMORROW trial of nintedanib comprised a randomised, placebo-controlled, 52-week period followed by a further blinded treatment period and an open-label extension. We assessed outcomes across these periods in patients randomised to nintedanib 150 mg twice daily or placebo at the start of TOMORROW. The annual rate of decline in FVC was -125.4 mL/year (95% CI -168.1 to -82.7) in the nintedanib group and -189.7 mL/year (95% CI -229.8 to -149.6) in the comparator group. The adverse event profile of nintedanib remained consistent throughout the studies. These results support a benefit of nintedanib on slowing progression of idiopathic pulmonary fibrosis beyond 52 weeks.

Trial registration: ClinicalTrials.gov NCT01170065 NCT00514683.

Keywords: idiopathic pulmonary fibrosis.

Conflict of interest statement

Competing interests: LR reports receipt of personal fees from Boehringer Ingelheim for being a coprincipal investigator and member of the steering committee for the INPULSIS trials; grants and personal fees for being an advisory board member from InterMune; personal fees from MedImmune, Roche and Takeda for being an advisory board member; consulting fees from Biogen Idec, Celgene, ImmuneWorks, Pliant Therapeutics and Sanofi-Aventis; speaker honoraria from Shionogi. MK reports receipt of grants and personal fees from Boehringer Ingelheim, InterMune and Roche. MS reports receipt of personal fees from Boehringer Ingelheim for being a member of the INPULSIS steering committee. BC reports receipt of grants, personal fees and non-financial support from Boehringer Ingelheim and InterMune; personal fees and non-financial support from Sanofi; grants from Cardif and MedImmune; and personal fees from AstraZeneca. A-MK reports receipt of grants (paid to her institution) and lecture fees from Boehringer Ingelheim. WAW reports receipt of grants (paid to his institution) from InterMune and travel costs for congresses from Boehringer Ingelheim, Roche and Bayer. ZX reports no competing interests. KB, SSt and MQ are employees of Boehringer Ingelheim. UC reports receipt of grants (paid to his institution); personal fees for consulting and lecture fees from Boehringer Ingelheim, InterMune and Bayer; and personal fees for consulting from AstraZeneca, Biogen, Centocor, FibroGen, Gilead, GlaxoSmithKline, Roche and UCB Celltech.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1

Annual rate of decline in FVC (A), Kaplan-Meier estimate of time to first acute exacerbation (B) and Kaplan-Meier estimate of time to death (C) over TOMORROW periods 1 and 2 and the open-label extension trial. Patients in the comparator group received placebo in period 1 of the TOMORROW trial and nintedanib 50 mg once daily in period 2. Patients entered the extension trial on the dose that they were receiving at the end of period 2, but had the option to increase dose to nintedanib 150 mg twice daily. Dose reduction from 150 mg twice daily to 100 mg twice daily and treatment interruption were permitted for the management of adverse events.