Effect of nintedanib in patients with systemic sclerosis-associated interstitial lung disease and risk factors for rapid progression
Toby M Maher,
Michael Kreuter,
Vanessa Smith,
Yannick Allanore,
Elizabeth R Volkmann,
Dinesh Khanna,
Christopher P Denton,
Anna-Maria Hoffmann-Vold,
Shervin Assassi,
Masataka Kuwana,
Margarida Alves,
Christian Stock,
Steven Sambevski
Affiliations
Toby M Maher
Keck School of Medicine, University of Southern California, Los Angeles, California, USA
Michael Kreuter
Center for Interstitial and Rare Lung Diseases, Pneumology and Respiratory Care Medicine, Thoraxklinik, University of Heidelberg and German Center for Lung Research, Heidelberg, Germany
Vanessa Smith
Department of Rheumatology, Ghent University Hospital, Ghent, Belgium
Yannick Allanore
Department of Rheumatology A, Descartes University, APHP, Cochin Hospital, Paris, France
Elizabeth R Volkmann
Division of Rheumatology, University of California, David Geffen School of Medicine, Los Angeles, California, USA
Dinesh Khanna
Division of Rheumatology, Scleroderma Program, University of Michigan, Ann Arbor, Michigan, USA
Christopher P Denton
University College London Division of Medicine, Centre for Rheumatology and Connective Tissue Diseases, London, UK
Anna-Maria Hoffmann-Vold
Inflammatory and Fibrotic Rheumatic Disease Research Area, Oslo University Hospital, Oslo, Norway
Shervin Assassi
Division of Rheumatology, University of Texas McGovern Medical School, Houston, Texas, USA
Masataka Kuwana
Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan
Margarida Alves
TA Inflammation Med, Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
Christian Stock
Global Biostatistics and Data Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany
Steven Sambevski
TA Inflammation Med, Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
Objective To investigate the rate of decline in forced vital capacity (FVC), and the effect of nintedanib on the rate of decline in FVC, in subjects with systemic sclerosis-associated interstitial lung disease (SSc-ILD) who had risk factors for rapid decline in FVC.Methods The SENSCIS trial enrolled subjects with SSc and fibrotic ILD of ≥10% extent on high-resolution CT. The rate of decline in FVC over 52 weeks was analysed in all subjects and in those with early SSc (<18 months since first non-Raynaud symptom), elevated inflammatory markers (C reactive protein ≥6 mg/L and/or platelets ≥330×109/L) or significant skin fibrosis (modified Rodnan skin score (mRSS) 15–40 or mRSS ≥18) at baseline.Results In the placebo group, the rate of decline in FVC was numerically greater in subjects with <18 months since first non-Raynaud symptom (−167.8 mL/year), elevated inflammatory markers (−100.7 mL/year), mRSS 15–40 (−121.7 mL/year) or mRSS ≥18 (−131.7 mL/year) than in all subjects (−93.3 mL/year). Nintedanib reduced the rate of FVC decline across subgroups, with a numerically greater effect in patients with these risk factors for rapid FVC decline.Conclusion In the SENSCIS trial, subjects with SSc-ILD who had early SSc, elevated inflammatory markers or extensive skin fibrosis had a more rapid decline in FVC over 52 weeks than the overall trial population. Nintedanib had a numerically greater effect in patients with these risk factors for rapid ILD progression.
