Effects of Nintedanib in Patients with Diffuse and Limited Cutaneous Systemic Sclerosis and Interstitial Lung Disease: Subgroup Analysis of the SENSCIS Trial

Masataka Kuwana¹, Kristin Highland ², Martina Gahlemann ³, Christopher Denton ⁴, Aryeh Fischer ⁵, Maureen Mayes ⁶, Virginia Steen ⁷, Dinesh Khanna ⁸, Yannick Allanore ⁹, Mannaig Girard ¹⁰, Margarida Alves ¹¹, Susanne Stowasser ¹¹ and Oliver Distler ¹², ¹Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan, Bunkyo-ku, Tokyo, Japan, ²Cleveland Clinic, Cleveland, Ohio, USA, Cleveland, OH, ³Boehringer Ingelheim (Schweiz) GmbH, Basel, Switzerland, Basel, Switzerland, ⁴University College London Division of Medicine, Centre for Rheumatology and Connective Tissue Diseases, London, UK, London, United Kingdom, ⁵University of Colorado School of Medicine, Denver, Colorado, USA, Denver, CO, ⁶Division of Rheumatology and Clinical Immunogenetics, University of Texas McGovern Medical School, Houston, Texas, USA, Houston, TX, ⁷Georgetown University, Washington, D.C., USA, Georgetown, ⁸Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA, Ann Arbor, ⁹Dept. of Rheumatology A, Descartes University, APHP, Cochin Hospital, Paris, France, Paris, France, ¹⁰Boehringer Ingelheim France S.A.S., Reims, France, Reims, France, ¹¹Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany, Ingelheim am Rhein, Germany, ¹²Dept. of Rheumatology, University Hospital Zürich, Zürich, Switzerland, Zürich, Switzerland

Meeting: ACR/ARP Annual Meeting 2019

Keywords: autoimmune diseases, interstitial lung disease, Scleroderma, therapy and fibrosis

Session Information

Date: Monday, November 11, 2019

Title: Systemic Sclerosis & Related Disorders – Clinical Poster II

Session Type: Poster Session (Monday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Patients with diffuse cutaneous systemic sclerosis (dcSSc) are at greater risk of developing interstitial lung disease (ILD) than patients with limited cutaneous systemic sclerosis (lcSSc). In the SENSCIS trial in patients with SSc-ILD, nintedanib reduced the rate of decline in forced vital capacity (FVC) vs placebo over 52 weeks, with no difference between groups in the change from baseline in modified Rodnan skin score (mRSS). We analyzed data from the SENSCIS trial in subgroups of patients with lcSSc or dcSSc.

Methods: Patients with SSc-ILD with onset of first non-Raynaud symptom < 7 years before screening and ≥10% fibrosis of the lungs on a high-resolution computed tomography (HRCT) scan were randomized to receive nintedanib 150 mg bid or placebo. We analyzed outcomes and adverse events over 52 weeks in subgroups of patients with lcSSc or dcSSc at baseline.

Results: Of 288 patients treated in each group, 153 (53.1%) and 146 (50.7%) in the nintedanib and placebo groups, respectively, had dcSSc. At baseline, in patients with dcSSc and lcSSc, respectively, mean (SD) FVC (mL) was 2461 (797) and 2542 (755), FVC % predicted was 70.5 (16.3) and 74.8 (16.8), and modified Rodnan skin score (mRSS) was 16.7 (8.8) and 5.2 (4.1). In the placebo group, the annual rate of FVC decline was numerically greater in patients with dcSSc than lcSSc (-112.0 vs -74.5 mL/year). Nintedanib reduced the rate of FVC decline both in patients with lcSSc and dcSSc. The treatment effect of nintedanib on FVC decline was numerically greater in patients with dcSSc than lcSSc, but no difference in the treatment effect between subgroups was detected (treatment-by-time-by-subgroup interaction p=0.42) (Figure). In the nintedanib and placebo groups, respectively, absolute declines in FVC >5% predicted at week 52 were seen in 22.2% and 28.8% of patients with dcSSc (OR 0.71 [95% CI 0.42, 1.20]) and 18.7% and 28.2% with lcSSc (OR 0.59 [0.33, 1.04]) (treatment-by-subgroup interaction p >0.05). Adjusted mean absolute changes from baseline in mRSS at week 52 in the nintedanib and placebo groups were -1.6 and -1.5 in patients with dcSSc (difference -0.2 [95% CI -1.2, 0.8]) and -2.7 and -2.5 in patients with lcSSc (difference -0.3 [-1.3, 0.8]; treatment-by-subgroup interaction p >0.05). The adverse event profile of nintedanib was similar between patients with dcSSc and lcSSc.

Conclusion: In the SENSCIS trial in patients with SSc-ILD, the rate of decline in FVC in patients who received placebo was greater in patients with dcSSc than lcSSc. Nintedanib reduced the rate of FVC decline both in patients with dcSSc and lcSSc. The treatment effect of nintedanib was numerically greater in patients with dcSSc than lcSSc, but statistical testing did not indicate heterogeneity in the treatment effect between the subgroups. No effect of nintedanib was demonstrated on skin fibrosis assessed using the mRSS.

Disclosure: M. Kuwana, Abbvie, 2, 8, Actelion, 2, 8, Actelion Pharmaceuticals, 2, 8, Astellas, 2, 8, Bayer, 5, Boehringer Ingelheim, 5, Boehringer-Ingelheim, 5, Chugai, 2, 5, 8, Corbus, 5, CSL Behring, 5, CSL Berling, 5, Eisai, 2, 8, Eli Lilly, 2, Janssen, 8, Japan Blood Products Organization, 8, MBL, 7, 8, Ono, 2, 8, Pfizer, 2, Reata, 5, Tanabe-Mitsubishi, 2, 8; K. Highland, Actelion Pharmaceuticals, 2, 8, 9, Bayer, 8, Bayer Healthcare, 8, Boehringer Ingelheim, 2, 5, 8, 9, Eiger Pharmaceuticals, 2, Genentech, 2, 8, Gilead Sciences, 8, Reata Pharmaceuticals, 2, United Therapeutics, 2, 8; M. Gahlemann, Boehringer Ingelheim, 3; C. Denton, Actelion, 5, Actelion Pharmaceuticals, 5, Actelion, GlaxoSmithKline, Bayer, Sanofi, lnventiva, Boehringer Ingelheim, Roche, Bristol Myers Squibb, CSL Behring, UCB, Leadiant Biosciences, 5, Bayer, 5, Boehringer Ingelheim, 5, Bristol Myers Squibb, 5, Bristol-Myers Squibb, 5, Corbus Pharmaceuticals, 5, CSL Behring, 2, 5, GlaxoSmithKline, 2, 5, Inventiva, 2, 5, Leadiant Biosciences, 2, 5, lnventiva, 5, Pfizer, 5, Roche, 5, Sanofi, 5, UCB, 5; A. Fischer, Boehringer Ingelheim, 5, Bristol Myers Squibb, 5, Bristol-Myers Squibb, 5, Hoffmann-La Roche, 5, Roche, 5; M. Mayes, Boehringer Ingelheim, 5, 8, 9, Corbus, 9, Corbus Pharma, 9, Eicos, 9, Eicos Sciences, 9, Galapagos, 5, 9, GlaxoSmithKline, 9, Mitsubishi Tanabe Pharma, 5, Mitsubishi-Tanabe, 5, Reata Pharma, 9, Reata Pharmaceuticals, 9, Sanofi, 9; V. Steen, Boehringer Ingelheim, 5, Corbus, 5, 9, CSL, 5, 9, CSL Behring, 2, 5, DSMB, 5, 9, Galapagos, 5, 9; D. Khanna, Acceleron, 5, 8, Acceleron Pharma, 5, Actelion, 5, 8, Actelion Pharmaceuticals, 5, Astra Zeneca, 5, Bayer, 2, 5, 8, Behring, 5, Blade, 5, Blade Therapeutics, 5, 8, Blade therapeutics, 5, BMS, 2, 5, 8, Boehringer Ingelham, 5, Boehringer Ingelheim, 5, 8, Boehringer-Ingelheim, 5, Bristol Myers Squibb, 2, 5, Bristol-Myers Squibb, 2, 5, Celegene, 5, Celgene, 5, 8, ChemomAB, 5, ChemomAb, 5, CiviBioPharma, Inc., 3, Corbus, 5, Corobus, 5, Corpus, 5, CSL Behring, 5, 8, Curizon, 5, Curzion, 5, Cytori, 5, 8, Eicos, 4, Eicos Sciences, 4, Eicos Sciences, Inc, 4, Eicos Sciences, Inc/ CiviBioPharma, Inc, 1, 4, Eicos Sciences, Inc/ CiviBioPharma, Inc., 1, Eicos, Inc, 4, Eicos, Inc., 5, 8, Eicos, INC., 4, Galapagos, 5, Genentech, 5, Genentech/Roche, 5, GlaxoSmithKline, 5, GSK, 5, Horizon, 2, 5, Mitsubishi Tanabe Pharma, 5, Mitsubishi Tanabe Pharma Dev America, 5, Mitsubishi Tanabe Pharma Development America, 5, Mitsubishi Tanabi, 5, NIH K24 and R01, 2, NIH / NIAMS K24 AR-063120, 2, NIH/NIAMS R01& K24, 2, Pfizer, 2, 5, Sanofi, 5, Sanofi Aventis, 5, Sanofi-Aventis, 5, 8, Sanofi-Aventis/Genzyme, 5, UCB, 5, UCB Pharma, 5; Y. Allanore, Actelion, 2, 5, Alpine, 2, 5, Bayer, 2, 5, BMS, 2, 5, Boehringer Ingelheim, 2, 5, Bristol Myers Squibb, 5, Bristol-Myers Squibb, 2, 5, Genentech Roche, 2, 5, Inventiva, 2, 5, Italfarmaco, 2, 5, Sanofi, 2, 5, Servier, 2, 5; M. Girard, Boehringer Ingelheim, 3; M. Alves, Boehringer Ingelheim, 3; S. Stowasser, Boehringer Ingelheim, 3; O. Distler, A. Menarini, 5, Abbvie, Acceleron, 5, Acceleron Pharma, 5, Actelion, 2, 5, 8, Actelion Pharmaceuticals, 2, 5, 8, 9, Amgen, 5, AnaMar, 2, 5, Bayer, 2, 5, 8, 9, Biogen Idec, 2, 5, Blade Therapeutics, 5, Boehringer Ingelheim, 2, 5, 8, 9, Catenion, 5, 9, ChemomAb, 2, 5, ChemomAB, 5, CSL Behring, 5, Ergonex, 5, espeRare Foundation, 2, 5, Genentech/Roche, 2, 5, GlaxoSmithKline, 5, GSK, 2, 5, Holds Patent mir-29 for the treatment of systemic sclerosis, 9, Inventiva, 2, 5, iQvia, 5, Italfarmaco, 2, 5, Italfarmco, 5, Lilly, 2, 5, med, 5, 8, medac, 5, Medac, 2, 5, MedImmune, 2, 5, Medscape, 5, 8, 9, Menarini, 8, Mepha, 8, Mitsubishi Tanabe, 2, 5, Mitsubishi Tanabe Pharma, 2, 5, MSD, 5, 8, Novartis, 2, 5, 8, 9, Patent, 9, Patent issued, 9, Pfizer, 2, 5, 8, Pharmacyclics, 2, 5, Roche, 5, 8, 9, Sanofi, 2, 5, Sinoxa, 2, 5, Target Bio Science, 5, Target BioScience, 5, UCB, 2, 5, 9, UCB in the area of potential treatments of scleroderma and its complications, 2, 5.

To cite this abstract in AMA style:

Kuwana M, Highland K, Gahlemann M, Denton C, Fischer A, Mayes M, Steen V, Khanna D, Allanore Y, Girard M, Alves M, Stowasser S, Distler O. Effects of Nintedanib in Patients with Diffuse and Limited Cutaneous Systemic Sclerosis and Interstitial Lung Disease: Subgroup Analysis of the SENSCIS Trial [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/effects-of-nintedanib-in-patients-with-diffuse-and-limited-cutaneous-systemic-sclerosis-and-interstitial-lung-disease-subgroup-analysis-of-the-senscis-trial/. Accessed .

« Back to ACR/ARP Annual Meeting 2019

ACR Meeting Abstracts - https://acrabstracts.org/abstract/effects-of-nintedanib-in-patients-with-diffuse-and-limited-cutaneous-systemic-sclerosis-and-interstitial-lung-disease-subgroup-analysis-of-the-senscis-trial/