Effect of Nintedanib in Patients with Systemic Sclerosis-associated Interstitial Lung Disease and Risk Factors for Rapid Decline in Forced Vital Capacity: Further Analyses of the SENSCIS Trial

Dinesh Khanna¹, Toby M Maher², Elizabeth Volkmann³, Yannick Allanore⁴, Vanessa Smith⁵, Shervin Assassi⁶, Michael Kreuter⁷, Anna-Maria Hoffmann-Vold⁸, Masataka Kuwana⁹, Christian Stock¹⁰, Margarida Alves¹¹, Steven Sambevski¹¹ and Christopher Denton¹², ¹University of Michigan, Ann Arbor, MI, ²National Heart and Lung Institute, Imperial College London, UK, National Institute for Health Research Clinical Research Facility, Royal Brompton Hospital, London, UK, and Keck School of Medicine, University of Southern California, Los Angeles, CA, ³Department of Medicine, Division of Rheumatology, University of California, David Geffen School of Medicine, Los Angeles, CA, ⁴Department of Rheumatology A, Descartes University, APHP, Cochin Hospital, Paris, France, ⁵Department of Rheumatology and Internal Medicine, Ghent University Hospital, Ghent, Belgium, ⁶University of Texas McGovern Medical School at Houston, Houston, TX, ⁷Center 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, ⁸Department of Rheumatology, Oslo University Hospital, Oslo, Norway, ⁹Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan, ¹⁰Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany, ¹¹Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany, Ingelheim, Germany, ¹²University College London Division of Medicine, Centre for Rheumatology and Connective Tissue Diseases, London, United Kingdom

Meeting: ACR Convergence 2021

Keywords: interstitial lung disease, Systemic sclerosis

Session Information

Date: Tuesday, November 9, 2021

Title: Systemic Sclerosis & Related Disorders – Clinical Poster III (1836–1861)

Session Type: Poster Session D

Session Time: 8:30AM-10:30AM

Background/Purpose: In the SENSCIS trial conducted in a population of subjects with systemic sclerosis-associated interstitial lung disease (SSc-ILD), with a mean time since onset of first non-Raynaud symptom of 3.5 years and 52% with diffuse cutaneous SSc (dcSSc), nintedanib reduced the rate of decline in FVC (mL/year) over 52 weeks by 44% versus placebo. Risk factors for a rapid decline in FVC in patients with SSc include early SSc, elevated inflammatory markers, significant skin involvement, and dcSSc. Patients with SSc with these risk factors for rapid progression of ILD are typically given immunosuppressants but not nintedanib. We analyzed the rate of decline in FVC and the effect of nintedanib on FVC decline in subjects with these risk factors in the SENSCIS trial.

Methods: In post-hoc analyses of data from the SENSCIS trial, we analyzed the rate of decline in FVC (mL/year) over 52 weeks in all subjects and in those with early SSc (< 18 months since onset of first non-Raynaud symptom), elevated inflammatory markers (C-reactive protein ≥6 mg/L and/or platelets ≥330 x 10⁹/L), or significant skin fibrosis using two approaches (modified Rodnan skin score [mRSS] 15-40 or mRSS >18) at baseline. We also analyzed the rate of decline in FVC over 52 weeks in subjects with one of these risk factors and dcSSc.

Results: Of 575 subjects analyzed, 79 (13.7%) had < 18 months since onset of first non-Raynaud symptom, 210 (36.5%) had elevated inflammatory markers, 172 (29.9%) had mRSS 15-40 and 118 (20.5%) had mRSS >18. Of 299 subjects with dcSSc, 29 (9.7%) had < 18 months since onset of first non-Raynaud symptom, 129 (43.1%) had elevated inflammatory markers, 162 (54.2%) had mRSS 15-40 and 118 (39.5%) had mRSS >18. In the placebo group, the rate of decline in FVC over 52 weeks was numerically greater in subjects with these risk factors for rapid decline in FVC compared with all subjects. Across the subgroups, the rate of decline in FVC was numerically lower in subjects treated with nintedanib than placebo (Figures).

Conclusion: The SENSCIS trial included a broad range of subjects with a fibrotic ILD complicating SSc, including those with risk factors for a rapid decline in FVC. In the placebo group, subjects with these risk factors had a more rapid decline in FVC over 52 weeks compared with the overall trial population. By targeting fibrosis with nintedanib, the rate of decline in FVC in patients with risk factors for FVC decline was reduced in patients treated with nintedanib than placebo.

Disclosures: D. Khanna, AbbVie, 2, Acceleron, 2, Actelion, 2, Amgen, 2, Bayer, 2, 5, Boehringer Ingelheim, 2, Bristol-Myers Squibb, 5, CiviBioPharma/Eicos Sciences, Inc, 12, Leadership/Equity position (Chief Medical Officer), Corbus, 2, CSL Behring, 2, Eicos Sciences, Inc, 11, Galapagos NV, 2, Genentech/Roche, 2, Gilead, 2, GlaxoSmithKline, 2, Horizon Therapeutics, 2, 5, Immune Tolerance Network, 5, Merck Sharp & Dohme, 2, Mitsubishi Tanabe Pharma, 2, National Institutes of Health, 5, Pfizer, 5, Sanofi-Aventis, 2, United Therapeutics, 2, Prometheus, 2, Theraly, 2, AstraZeneca, 2; T. Maher, Apellis, 2, Bayer, 2, Biogen, 2, Blade Therapeutics, 2, Boehringer Ingelheim, 2, Bristol-Myers Squibb, 2, Galapagos NV, 2, Galecto, 2, GlaxoSmithKline, 2, Indalo, 2, Novartis, 2, Respivent, 2, Roche, 2, Trevi, 2, UCB, 2; E. Volkmann, Boehringer Ingelheim, 2, 6, Corbus, 5, Forbius, 5, Kadmon, 5; Y. Allanore, Bayer, 2, Boehringer Ingelheim, 2, 12, Clinical trial investigator, Roche, 2, Chemomab, 2, Curzion, 2, Sanofi, 2, 12, Clinical trial investigator; V. Smith, Boehringer Ingelheim, 2, 6, Janssens, 2, 6; S. Assassi, Novartis, 2, Boehringer Ingelheim, 2, 5, 6, 12, Travel, Corbus, 2, Integrity Continuing Education, 6, Medscape, 6, Momenta, 5, CSL Behring, 2, Janssen, 5, Abbvie, 2; M. Kreuter, Boehringer Ingelheim, 2, 5, Galapagos NV, 2, Roche, 2, 5; A. Hoffmann-Vold, Actelion, 1, 2, 6, Arxx Therapeutics, 1, 2, Bayer, 5, Boehringer Ingelheim, 1, 2, 5, 6, Lilly, 6, Medscape, 2, 6, Merck Sharp & Dohme, 6, Roche, 6; M. Kuwana, Boehringer Ingelheim, 5, 6, One Pharmaceuticals, 5, 6, Chugai, 6, Janssen, 6, Astellas, 6, Tanabe Mitsubishi, 6, Pfizer, 6, Nippon Shinyaku, 6, Corbus, 2, Mochida, 2, Kissei, 2, MBL, 9; C. Stock, Boehringer Ingelheim, 3; M. Alves, Boehringer Ingelheim, 3; S. Sambevski, Boehringer Ingelheim, 3; C. Denton, Acceleron, 2, 6, Actelion, 2, 6, Arxx Therapeutics, 2, 6, Boehringer Ingelheim, 2, 6, Bristol-Myers Squibb, 2, 6, Corbus, 2, 6, CSL Behring, 2, 6, Galapagos NV, 2, 6, GlaxoSmithKline, 2, 6, Horizon, 2, 6, Inventiva, 2, 6, Roche, 2, 6, Sanofi, 2, 6, Servier, 2.

To cite this abstract in AMA style:

Khanna D, Maher T, Volkmann E, Allanore Y, Smith V, Assassi S, Kreuter M, Hoffmann-Vold A, Kuwana M, Stock C, Alves M, Sambevski S, Denton C. Effect of Nintedanib in Patients with Systemic Sclerosis-associated Interstitial Lung Disease and Risk Factors for Rapid Decline in Forced Vital Capacity: Further Analyses of the SENSCIS Trial [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/effect-of-nintedanib-in-patients-with-systemic-sclerosis-associated-interstitial-lung-disease-and-risk-factors-for-rapid-decline-in-forced-vital-capacity-further-analyses-of-the-senscis-trial/. Accessed .

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