Pneumologie 2021; 75(S 01): S31-S32
DOI: 10.1055/s-0041-1723316
Latebreaking Abstracts 2021

Does HRCT pattern influence the effect of nintedanib in patients with progressive fibrosing interstitial lung diseases?[*]

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
,
K K Brown
2   National Jewish Health, Pulmonary, Critical Care and Sleep Medicine, Denver, Co, USA
,
S LF Walsh
3   National Heart and Lung Institute, Imperial College, London, UK
,
A Devaraj
4   Department of Radiology, Royal Brompton and Harefield NHS Foundation Trust, London, UK
,
J W Song
5   University of Ulsan College of Medicine, Asan Medical Center, Pulmonary and Critical Care Medicine, Seoul, South Korea
,
W A Wuyts
6   Unit for Interstitial Lung Diseases, Department of Respiratory Medicine, University Hospitals Leuven, Leuven, Belgium
,
C Valenzuela
7   Hospital Universitario de La Princesa, Madrid, Spain
,
R G Goeldner
8   Boehringer Ingelheim Pharma GmbH & Co. Kg, Biberach, Germany
,
S Stowasser
9   Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
,
R Schlenker-Herceg
10   Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Ct, USA
,
A U Wells
11   National Institute for Health Research Respiratory Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust, and National Heart and Lung Institute, Imperial College, London, UK
› Author Affiliations
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    Rationale: Several studies have suggested that the progression of fibrosing ILDs is more rapid in patients with a usual interstitial pneumonia (UIP) pattern on HRCT. In the INBUILD trial, nintedanib slowed the rate of decline in FVC in subjects with fibrosing ILDs and a progressive phenotype. We assessed the effect of nintedanib in subgroups by HRCT pattern.

    Methods: Subjects with a physician-diagnosed fibrosing ILD other than IPF, features of diffuse fibrosing lung disease (reticular abnormality with traction bronchiectasis, with or without honeycombing) of > 10% extent on HRCT, FVC ≥ 45% predicted, and DLco ≥ 30%–<80% predicted, who met protocol-defined criteria for progression of ILD in the 24 months before screening, were randomized to receive nintedanib or placebo stratified by HRCT pattern (UIP-like or other fibrotic patterns) based on central review. In pre-specified analyses, we assessed the effects of nintedanib in subgroups of subjects with UIP-like and other fibrotic patterns on HRCT at baseline.

    Results: At baseline, 412 subjects (nintedanib 206; placebo 206) had a UIP-like fibrotic pattern on HRCT and 251 subjects (nintedanib 126; placebo 125) had other fibrotic patterns on HRCT. Mean (SD) FVC at baseline was 2369 (741) and 2268 (719) mL in subjects with UIP-like and other fibrotic patterns on HRCT, respectively. In subjects who received placebo, the adjusted mean annual rate (SE) of decline in FVC was − 209.2 (19.1) mL/year in subjects with UIP-like and − 155.4 (23.6) mL/year in subjects with other fibrotic patterns on HRCT. The difference between the nintedanib and placebo groups in the annual rate of decline in FVC was 127.8 (95% CI: 74.3, 181.2) mL/year in subjects with UIP-like and 75.4 (95% CI: 9.5, 141.4) mL/year in subjects with other fibrotic patterns on HRCT (treatment-by-subgroup-by-time interaction p = 0.23) ([Table 1]). The effects of nintedanib vs. placebo on change from baseline in K-BILD questionnaire total score at week 52, time to acute exacerbation of ILD or death over 52 weeks, and time to death over 52 weeks between the subgroups by HRCT pattern are shown in [Table 1].

    Tab. 1 

    UIP-like fibrotic pattern on HRCT

    Other fibrotic patterns on HRCT

    Nintedanib (n = 206)

    Placebo
    (n = 206)

    Nintedanib (n = 126)

    Placebo (n = 125)

    Adjusted mean (SE) annual rate of decline in FVC (mL/year)

    − 81.5 (19.4)

    − 209.2 (19.1)

    − 79.9 (24.0)

    − 155.4 (23.6)

    Difference (95% CI)

    127.8 (74.3, 181.2)

    75.4 (9.5, 141.4)

    Treatment-by-subgroup-by-time interaction

    p = 0.23

    Adjusted mean (SE) change from baseline in K-BILD questionnaire total score at week 52

    0.95 (0.76)

    − 0.58 (0.76)

    − 0.11 (0.96)

    − 1.11 (0.94)

    Difference (95% CI)

    1.53 (− 0.58, 3.65)

    1.00 (− 1.64, 3.63)

    Treatment-by-subgroup interaction

    p = 0.76

    Acute exacerbation of ILD or death over 52 weeks, n (%)

    17 (8.3)

    25 (12.1)

    9 (7.1)

    7 (5.6)

    HR (95% CI)

    0.67 (0.36, 1.24)

    1.26 (0.47, 3.39)

    Treatment-by-subgroup interaction

    p = 0.28

    Death over 52 weeks, n (%)

    11 (5.3)

    16 (7.8)

    5 (4.0)

    1 (0.8)

    HR (95% CI)

    0.68 (0.32, 1.47)

    5.03 (0.59, 43.02)

    Treatment-by-subgroup interaction

    p = 0.09

    Conclusions: In the INBUILD trial, the effect of nintedanib on slowing the rate of FVC decline was consistent between subjects with UIP-like and other fibrotic patterns on HRCT.


    #

    * Previously presented at ATS2020.



    Publication History

    Article published online:
    30 April 2021

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