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Randomized Controlled Trial
. 2023 Feb;9(1):e002859.
doi: 10.1136/rmdopen-2022-002859.

Effect of nintedanib in patients with systemic sclerosis-associated interstitial lung disease and risk factors for rapid progression

Dinesh Khanna  1 , Toby M Maher  2   3 , Elizabeth R Volkmann  4 , Yannick Allanore  5 , Vanessa Smith  6   7   8 , Shervin Assassi  9 , Michael Kreuter  10   11 , Anna-Maria Hoffmann-Vold  12 , Masataka Kuwana  13 , Christian Stock  14 , Margarida Alves  15 , Steven Sambevski  15 , Christopher P Denton  16
Affiliations
Randomized Controlled Trial

Effect of nintedanib in patients with systemic sclerosis-associated interstitial lung disease and risk factors for rapid progression

Dinesh Khanna et al. RMD Open. 2023 Feb.

Abstract

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.

Keywords: Autoimmune Diseases; Pulmonary Fibrosis; Scleroderma, Systemic; Therapeutics.

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Conflict of interest statement

Competing interests: DK reports grants from Bristol Myers Squibb, Horizon Therapeutics and Pfizer; consulting fees from AbbVie, BI, Bristol Myers Squibb, CSL Behring, Genentech, Horizon Therapeutics, Janssen, Prometheus, Talaris and Theraly; fees for presentations from AbbVie, BI, CSL Behring, Genentech, Horizon Therapeutics and Janssen; has a leadership or fiduciary role with Eicos; has received royalties or licences for the University of California Los Angeles Scleroderma Clinical Trials Consortium (SCTC) Gastrointestinal Tract instrument 2.0; and owns stock in Eicos. TMM reports consulting fees from AstraZeneca, Bayer, Blade Therapeutics, BI, Bristol Myers Squibb, Galapagos, Galecto, GlaxoSmithKline, IQVIA, Pliant, Respivant Sciences, Roche/Genentech, Theravance Biopharma and Veracyte; and fees for presentations from BI and Roche/Genentech. ERV reports grants from BI, Forbius, Kadmon and Horizon; and fees from BI for serving on advisory boards and for presentations. YA reports consulting fees from BI and Sanofi; fees for presentations from AbbVie, BI and Janssen; and has participated on Data Safety Monitoring Boards or advisory boards for BI, Chemomab, Curzion, Medsenic, Menarini, Prometheus and Sanofi. VS reports grants paid to her institution from the Belgian Fund for Scientific Research in Rheumatic Diseases, Research Foundation Flanders, BI and Janssen-Cilag; consulting fees and fees for presentations paid to herself and to her institution from BI; consulting fees paid to her institution from Janssen-Cilag; fees for presentations paid to her institution from Janssen-Cilag and UCB; support for travel paid to her institution by BI; and holds unpaid roles with the ACR and EULAR study groups on microcirculation, ERN-ReCONNET and the SCTC working group on capillaroscopy. SA reports grants paid to his institution from BI, Janssen and Momenta; consulting fees from AbbVie, AstraZeneca, BI, Corbus, CSL Behring and Novartis; and fees for presentations from Integrity Continuing Education. MKreuter reports grants, consulting fees and fees for presentations from BI and Roche; and holds leadership or fiduciary roles with Deutsche gesellschaft für Pneumologie, the European Respiratory Society and the German Respiratory Society. A-MH-V reports grants from BI; consulting fees from Arxx Therapeutics, Bayer, BI, Janssen, Lilly, Medscape, Merck Sharp & Dohme and Roche; fees for presentations from Arxx Therapeutics, Bayer, BI, Janssen, Lilly, Medscape, Merck Sharp & Dohme and Roche; support for travel from Actelion, BI, Medscape and Roche; and holds leadership or fiduciary roles with EUSTAR, the Nordic PH vision group and the Norwegian SSc study group. MKuwana reports grants paid to his institution from BI, MBL and Ono Pharmaceutical; consulting fees from BI, Chugai, Corbus and Mochida; fees for presentations from AbbVie, Asahi Kasei, Astellas, Bayer, BI, Chugai, Eisai, Janssen, Mitsubishi Tanabe and Ono Pharmaceutical; and has received royalties or licences from MBL. CS, MA and SS are employees of BI. CPD reports grants from Arxx Therapeutics, CSL Behring, GlaxoSmithKline, Inventiva and Servier; consulting fees from AbbVie, Acceleron, Bayer, BI, Corbus, CSL Behring, GlaxoSmithKline, Horizon Therapeutics, Inventiva, Roche and Sanofi; and fees for presentations from BI, Corbus and Janssen.

Figures

Figure 1
Figure 1
Rate of decline in FVC (mL/year) over 52 weeks (A) in all subjects and in subjects with risk factors for rapid decline in FVC at baseline and (B) in all subjects and in subjects with dcSSc and risk factors for rapid decline in FVC at baseline in the SENSCIS trial. *C reactive protein ≥6 mg/L and/or platelets ≥330×109/L. dcSSc, diffuse cutaneous systemic sclerosis; FVC, forced vital capacity; mRSS, modified Rodnan skin score.
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