Effects of nintedanib by inclusion criteria for progression of interstitial lung disease

Abstract

Background: The INBUILD trial investigated nintedanib versus placebo in patients with progressive fibrosing interstitial lung diseases (ILDs). We investigated the decline in forced vital capacity (FVC) in subgroups based on the inclusion criteria for ILD progression.

Methods: Subjects had a fibrosing ILD other than idiopathic pulmonary fibrosis and met the following criteria for ILD progression within the 24 months before screening despite management deemed appropriate in clinical practice: Group A, relative decline in FVC ≥10% predicted; Group B, relative decline in FVC ≥5-<10% predicted with worsened respiratory symptoms and/or increased extent of fibrosis on high-resolution computed tomography (HRCT); Group C, worsened respiratory symptoms and increased extent of fibrosis on HRCT only.

Results: In the placebo group, the rates of FVC decline over 52 weeks in Groups A, B and C, respectively, were -241.9, -133.1 and -115.3 mL per year in the overall population (p=0.0002 for subgroup-by-time interaction) and -288.9, -156.2 and -100.1 mL per year among subjects with a usual interstitial pneumonia (UIP)-like fibrotic pattern on HRCT (p=0.0005 for subgroup-by-time interaction). Nintedanib had a greater absolute effect on reducing the rate of FVC decline in Group A than in Group B or C. However, the relative effect of nintedanib versus placebo was consistent across the subgroups (p>0.05 for heterogeneity).

Conclusions: The inclusion criteria used in the INBUILD trial, based on FVC decline or worsening of symptoms and extent of fibrosis on HRCT, were effective at identifying patients with progressive fibrosing ILDs. Nintedanib reduced the rate of decline in FVC across the subgroups based on the inclusion criteria related to ILD progression.

Trial registration: ClinicalTrials.gov NCT02999178.

Conflict of interest statement

Conflict of interest: T.M. Maher reports grants and personal fees (for serving as a board member or consultant, or working on clinical trials) from UCB and GlaxoSmithKline, and personal fees (for serving as a board member or consultant, or working on clinical trials) from Apellis, Boehringer Ingelheim, Roche, Bayer, Biogen Idec, Galapagos, Indalo, Galecto, Blade, Bristol-Myers Squibb, Novartis, Respivent and Trevi, outside the submitted work. Conflict of interest: K.K. Brown reports grants from NHLBI, serves on the board of the Open Source Imaging Consoritum (OSIC), and reports personal fees from Biogen, Galecto, Third Pole, Galapagos, Boehringer Ingelheim, Theravance, Lifemax, Pliant, Blade Therapeutics, Huitai Biomedicine, Lilly, Dispersol, DevPro Biopharma and Humanetics, outside the submitted work. Conflict of interest: M. Kreuter reports grants and personal fees from Boehringer Ingelheim and Roche, and personal fees from Galapagos, outside the submitted work. Conflict of interest: A. Devaraj reports personal fees from Boehringer Ingelheim, during the conduct of the study; and personal fees from Boehringer Ingelheim, GSK, Roche, Galapagos and Galecto Biotech, outside the submitted work. Conflict of interest: S.L.F. Walsh reports personal fees for consultancy from Sanofi-Aventis, Galapagos and OSIC, personal fees for advisory board work from Roche, grants and personal fees for steering committee work from Boehringer Ingelheim, and personal fees for lectures from Bracco, outside the submitted work. Conflict of interest: L.H. Lancaster reports grants and other (speaker for disease state education, advisory board) from Genentech, grants and other (speaker for disease state education) from Boehringer Ingelheim, and grants from Novartis, Celgene and Bellerophon, outside the submitted work. Conflict of interest: E.A. Belloli reports grants from Boehringer Ingelheim, during the conduct of the study; and personal fees for consultancy from Boehringer Ingelheim, outside the submitted work. Conflict of interest: M. Padilla reports grants and personal fees for consultancy from Boehringer Ingelheim, and personal fees for lectures from Genentech, Vindico and France Foundation, outside the submitted work. Conflict of interest: J. Behr reports personal fees for consultancy and lectures from Actelion, Bayer, Boehringer Ingelheim and Roche, and personal fees for consultancy from Galapagos, Biogen, BMS and Pliant, outside the submitted work; and is a member of national and international guideline committees for IPF and other interstitial lung diseases. Conflict of interest: R-G. Goeldner is an employee of Boehringer Ingelheim Pharma GmbH & Co. KG. Conflict of interest: K. Tetzlaff is an employee of Boehringer Ingelheim International GmbH. Conflict of interest: R. Schlenker-Herceg is an employee of Boehringer Ingelheim Pharmaceuticals, Inc. Conflict of interest: K.R. Flaherty reports grants and personal fees for consultancy from Boehringer Ingelheim and Roche/Genentech, and personal fees for consultancy from FibroGen, Veracyte, Sanofi-Genzyme, Respivant, Bellerophon, Blade Therapeutics and Celgene, outside the submitted work.

Copyright ©The authors 2022.

Figures

FIGURE 1

Rate of decline in forced vital capacity (FVC) (mL per year) over 52 weeks in the placebo group by criteria for interstitial lung disease progression in a) the overall population, b) subjects with a usual interstitial pneumonia-like fibrotic pattern on high-resolution computed tomography (HRCT) and c) subjects with other fibrotic patterns on HRCT.

FIGURE 2

Relative effect of nintedanib versus placebo on the rate of decline in forced vital capacity (FVC) (mL per year) over 52 weeks by inclusion criteria for interstitial lung disease progression in a) the overall population, b) subjects with a usual interstitial pneumonia-like fibrotic pattern on high-resolution computed tomography (HRCT) and c) subjects with other fibrotic patterns on HRCT.