Pneumologie 2022; 76(S 01): S24
DOI: 10.1055/s-0042-1747740
Abstracts

Decline in forced vital capacity as a surrogate for mortality in patients with fibrosing interstitial lung diseases* 

Authors

  • J Behr

    1   Medizinische Klinik und Poliklinik V, University of Munich and Asklepios Klinik München-Gauting, Member of the German Centre for Lung Research, Germany

  • T M Maher

    2   Keck School of Medicine, University of Southern California, Los Angeles, California, USA

  • E Bendstrup

    3   Centre for Rare Lung Diseases, Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark

  • M Kreuter

    4   Center for Interstitial and Rare Lung Diseases, Pneumology and Respiratory Care Medicine, Thoraxklinik, University of Heidelberg, Member of the German Center for Lung Research, Heidelberg, Germany

  • F J Martinez

    5   Weill Cornell Medicine, New York, New York, USA

  • P J Sime

    6   Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA

  • S Stowasser

    7   Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany

  • F Voss

    8   Boehringer Ingelheim Pharma GmbH & Co. Kg, Ingelheim am Rhein, Germany

  • C Stock

    8   Boehringer Ingelheim Pharma GmbH & Co. Kg, Ingelheim am Rhein, Germany

This abstract is funded by: These trials were funded by Boehringer Ingelheim.
Further Information
Also available at
 
 

Rationale The use of surrogate endpoints in clinical trials enables the determination of meaningful treatment effects in a more efficient manner than applying the endpoint of ultimate interest. We used data from clinical trials of nintedanib in patients with fibrosing ILDs to assess decline in forced vital capacity (FVC) as a surrogate for mortality.

Methods Data from patients who received nintedanib or placebo in the placebo-controlled periods of clinical trials in patients with IPF (TOMORROW, INPULSIS-1 and -2, and a Phase IIIb trial with a placebo-controlled period of up to 12 months [NCT01979952]), systemic sclerosis-associated ILD (SENSCIS) and progressive fibrosing ILDs other than IPF (INBUILD) were pooled. Using joint models for longitudinal and time-to-event data, the association between change in FVC % predicted and time to death over a 52-week period was assessed. Both the change in FVC % predicted and the rate of change (i.e. linear slope) in FVC % predicted were modelled longitudinally and estimates were applied as predictors in survival models through an association structure.

Results The pooled analysis included 2553 patients (1380 treated with nintedanib, 1173 treated with placebo). The differences between the nintedanib and placebo groups in the absolute change in FVC % predicted and in the rate of change in FVC % predicted over 52 weeks were 2.87 (95% CI: 2.23, 3.51; p<0.0001) and 2.84 (95% CI: 2.20, 3.49; p<0.0001), respectively. Over 52 weeks, 63 patients (4.6%) in the nintedanib group and 65 patients (5.5%) in the placebo group died. In the pooled dataset, both the decrease in FVC % predicted and the rate of decline in FVC % predicted were associated with an increased risk of death over 52 weeks (HR 1.24 [95% CI, 1.17, 1.32] per 5-unit decrease and HR 1.79 [95% CI, 1.57, 2.03] per 5-unit decrease, respectively) (Table).

Conclusions Data from clinical trials of nintedanib in patients with fibrosing ILDs demonstrate a strong association between decline in FVC % predicted and death over 52 weeks. These results suggest that slowing FVC decline reduces the risk of death in patients with fibrosing ILDs and support the use of FVC decline as a surrogate for mortality in clinical trials.

Presented at ATS 2021

Zoom
Abb. 1 This abstract is funded by:These trials were funded by Boehringer Ingelheim *presented at ATS 2021;Am J Respir Crit Care Med 2021;203:A1851; presenting on behalf of the authors.

Publication History

Article published online:
11 May 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
Zoom
Abb. 1 This abstract is funded by:These trials were funded by Boehringer Ingelheim *presented at ATS 2021;Am J Respir Crit Care Med 2021;203:A1851; presenting on behalf of the authors.