Meta-Analysis of Effect of Nintedanib on Reducing FVC Decline Across Interstitial Lung Diseases

Francesco Bonella*, Vincent Cottin, Claudia Valenzuela, Marlies Wijsenbeek, Florian Voss, Klaus B. Rohr, Susanne Stowasser, Toby M. Maher

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Introduction: The effect of nintedanib on slowing the rate of decline in forced vital capacity (FVC) has been investigated in randomized placebo-controlled trials in subjects with idiopathic pulmonary fibrosis (IPF), other progressive fibrosing interstitial lung diseases (ILDs), and ILD associated with systemic sclerosis (SSc-ILD). We assessed the consistency of the effect of nintedanib on the rate of decline in FVC over 52 weeks across four placebo-controlled phase III trials. Methods: We used data on FVC decline from the INPULSIS-1 and INPULSIS-2 trials in subjects with IPF, the INBUILD trial in subjects with progressing fibrosing ILDs other than IPF, and the SENSCIS trial in subjects with SSc-ILD. In each trial, the primary endpoint was the annual rate of decline in FVC (mL/year) assessed over 52 weeks. We performed fixed effect and random effects meta-analyses based on the relative treatment effect of nintedanib versus placebo on the rate of decline in FVC (mL/year) over 52 weeks. Heterogeneity of the relative treatment effect of nintedanib across populations was assessed using the I2 statistic, τ2 and corresponding p value from a Q test for heterogeneity. Results: The combined analysis comprised 1257 subjects treated with nintedanib and 1042 subjects who received placebo. Nintedanib reduced the rate of decline in FVC (mL/year) over 52 weeks by 51.0% (95% CI 39.1, 63.0) compared with placebo. The relative effect (95% CI) was the same using the fixed effect and random effects models. There was no evidence of heterogeneity in the relative treatment effect of nintedanib across the populations studied (I2 = 0%, τ2 = 0, p = 0.93). Conclusions: A meta-analysis of data from four placebo-controlled trials demonstrated that nintedanib approximately halved the rate of decline in FVC over 52 weeks across subjects with different forms of pulmonary fibrosis, with no evidence of heterogeneity in its relative treatment effect across patient populations. Graphical abstract: [Figure not available: see fulltext.].

Original languageEnglish
Pages (from-to)3392-3402
Number of pages11
JournalAdvances in Therapy
Volume39
Issue number7
Early online date14 May 2022
DOIs
Publication statusPublished - Jul 2022

Bibliographical note

Funding Information:
Writing assistance was provided by Julie Fleming and Wendy Morris of FleishmanHillard, London, UK, which was contracted and funded by BI. The authors were fully responsible for all content and editorial decisions, were involved at all stages of development and provided their approval on the final version.

Funding Information:
Open Access funding enabled and organized by Projekt DEAL. The INPULSIS, SENSCIS and INBUILD trials were funded by Boehringer Ingelheim International GmbH (BI). BI is funding the Rapid Service Fees for this manuscript.

Publisher Copyright:
© 2022, The Author(s).

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