Efficacy and Safety of Nintedanib in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease by Use of Mycophenolate at Baseline: Subgroup Analysis of the SENSCIS Trial

Kristin Highland¹, Oliver Distler ², Masataka Kuwana ³, Yannick Allanore ⁴, Shervin Assassi ⁵, Arata Azuma ⁶, Arnaud Bourdin ⁷, Christopher Denton ⁸, Jörg Distler ⁹, Anna Maria Hoffmann-Vold ¹⁰, Dinesh Khanna ¹¹, Maureen Mayes ⁵, Ganesh Raghu ¹², Madelon Vonk ¹³, Martina Gahlemann ¹⁴, Mannaig Girard ¹⁵, Susanne Stowasser ¹⁶, Donald Zoz ¹⁷, Aryeh Fischer ¹⁸ and Toby Maher ¹⁹, ¹Cleveland Clinic, Cleveland, Ohio, USA, Cleveland, OH, ²Dept. of Rheumatology, University Hospital Zürich, Zürich, Switzerland, Zürich, Switzerland, ³Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan, Bunkyo-ku, Tokyo, Japan, ⁴Dept. of Rheumatology A, Descartes University, APHP, Cochin Hospital, Paris, France, Paris, France, ⁵Division of Rheumatology and Clinical Immunogenetics, University of Texas McGovern Medical School, Houston, Texas, USA, Houston, TX, ⁶Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan, Tokyo, Japan, ⁷PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214 and Department of Respiratory Diseases, University of Montpellier, CHU Montpellier, Montpellier, France, Montpellier, ⁸University College London Division of Medicine, Centre for Rheumatology and Connective Tissue Diseases, London, UK, London, United Kingdom, ⁹Department of Internal Medicine 3 – Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen, Erlangen, Germany, Erlangen, Germany, ¹⁰Department of Rheumatology, Oslo University Hospital, Oslo, Norway, Oslo, Norway, ¹¹Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA, Ann Arbor, ¹²University of Washington, Seattle, USA, Seattle, ¹³Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands, Nijmegen, Gelderland, Netherlands, ¹⁴Boehringer Ingelheim (Schweiz) GmbH, Basel, Switzerland, Basel, Switzerland, ¹⁵Boehringer Ingelheim France S.A.S., Reims, France, Reims, France, ¹⁶Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany, Ingelheim am Rhein, Germany, ¹⁷Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA, Ridgefield, CT, ¹⁸University of Colorado School of Medicine, Denver, Colorado, USA, Denver, CO, ¹⁹National Heart and Lung Institute, Imperial College London, UK and National Institute for Health Research Clinical Research Facility, Royal Brompton Hospital, London, UK, London, United Kingdom

Meeting: 2019 ACR/ARP Annual Meeting

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

Session Information

Date: Monday, November 11, 2019

Title: 4M097: Systemic Sclerosis & Related Disorder – Clinical II: Cardiopulmonary Involvement (1830–1835)

Session Type: ACR Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: In the SENSCIS trial in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), nintedanib reduced the annual rate of decline in forced vital capacity (FVC) vs placebo (-52.4 vs -93.3 mL/year; difference 41.0 mL/year [95% CI 2.9, 79.0]; p=0.04), with adverse events that were consistent with the profile observed in patients with IPF. In many countries, mycophenolate is commonly used in the treatment of SSc-ILD. We analyzed the efficacy and safety of nintedanib in the SENSCIS trial by use of mycophenolate at baseline.

Methods: Subjects with SSc-ILD with ≥10% fibrosis of the lungs on HRCT were randomized to receive nintedanib 150 mg bid or placebo. Patients who had received stable therapy with mycophenolate for ≥6 months prior to randomization were eligible to participate. We analyzed lung function outcomes and adverse events over 52 weeks in subgroups of patients who were and were not taking mycophenolate at baseline.

Results: In the nintedanib and placebo groups, respectively, 139 (48.3%) and 140 (48.6%) of patients were taking mycophenolate at baseline. In patients taking and not taking mycophenolate at baseline, respectively, mean (SD) FVC (mL) was 2539 (770) and 2463 (784) and FVC % predicted was 70.8 (16.0) and 74.2 (17.1). In patients who received placebo, the mean (SE) rate of decline in FVC over 52 weeks was -66.5 (19.3) mL/year in patients taking mycophenolate at baseline and -119.3 (19.0) mL/year in patients not taking mycophenolate at baseline. Nintedanib reduced the rate of FVC decline both in patients who were and were not taking mycophenolate at baseline. The treatment effect of nintedanib was numerically greater in patients who were not taking mycophenolate at baseline, but statistical testing did not indicate heterogeneity in the treatment effect between subgroups (p=0.45) (Figure). In post-hoc analyses, in the nintedanib and placebo groups, respectively, absolute declines in FVC >5% predicted were seen in 15.2% and 25.7% of patients taking mycophenolate at baseline (OR 0.52 [95% CI 0.29, 0.95]) and 25.5% and 31.1% of those not taking mycophenolate at baseline (OR 0.76 [0.46, 1.26]). The adverse event profile of nintedanib was similar irrespective of mycophenolate use at baseline (Table). The proportion of patients treated with nintedanib who had adverse events leading to discontinuation of trial drug was no higher in patients taking mycophenolate at baseline than in those who were not (Table).

Conclusion: In the SENSCIS trial in patients with SSc-ILD, nintedanib reduced the rate of decline in FVC both in patients who had not taken mycophenolate and in patients who had taken a stable dose of mycophenolate for ≥6 months prior to randomization. The treatment effect of nintedanib was numerically greater in patients who were not taking mycophenolate at baseline. Careful interpretation of the data in the subgroups by use of mycophenolate is warranted as patients were not randomized by use of mycophenolate and the patients using mycophenolate at baseline had tolerated it for ≥6 months prior to entering the trial. The adverse event profile of nintedanib was similar irrespective of mycophenolate use.

Disclosure: 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; 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; 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; 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; S. Assassi, Bayer, 2, Boehringer Ingelheim, 2, 5, 8, Integrity Continuing Education, 8, 9, Medscape, 8, 9, Momenta, 2; A. Azuma, Asahikasei Pharma Co., 5, 9, Boehringer Ingelheim, 5, 9, Shionogi & Co., Ltd, 5, 9, Taiho Pharmaceutical Co., Ltd, 5, 9; A. Bourdin, AstraZeneca, 5, 9, Novartis, 5, 9, Chiesi Pharmaceuticals, 5, 9, Actelion, 5, 9, GlaxoSmithKline, 2, 5, 9, Boehringer Ingelheim, 2, 5, 9, Regeneron, 5, 9, Gilead Sciences, 9, Roche, 5, 9, Teva, 5, 9; 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; J. Distler, 4D Science, 4, Actelion, 5, Actelion Pharmaceuticals, 5, Active Biotech, 2, 5, AnaMar, 2, 5, Array Biopharma, 2, aTyr, 2, Bayer, 2, 5, BMS, 2, Boehringer Ingelheim, 2, 5, Bristol-Myers Squibb, 2, Celgene, 2, 5, Galapagos, 2, 5, GlaxoSmithKline, 2, 5, Inventiva, 2, 5, JB Therapeutics, 5, medac, 5, Medac, 5, Novartis, 2, Pfizer, 5, RedX, 2, RuiYi, 5, Sanofi, 2, Sanofi-Aventis, 2, UCB, 2, 5; A. Hoffmann-Vold, Actelion, 5, 8, Boehringer Ingelheim, 2, 5, 8, GSK, 5, 8; 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; 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; G. Raghu, Avalyn, 9, Bellerophan, 9, BI, 5, Biogen, 9, BMS, 9, Boehringer Ingelheim, 5, Bristol-Myers Squibb, 9, Fibrogen, 9, Gilead Sciences, 9, NIH, 2, Nitto, 9, Promedior, 9, Revistan, 9, Roche, 9, Roche/Genentech, 9, Roche-Genentech, 5, Sanofi, 9, Veracyte, 9; M. Vonk, Actelion, 2, 5, 8, actelion, 2, 5, 8, Actelion Pharmaceuticals, 2, 5, 8, Boehringer Ingelheim, 5, 8, Boehringer ingelheim, 5, 8, Ferrer, 2, Ferrer International, 2, Ferrier, 2, GSK, 5, 6, Roche, 8; M. Gahlemann, Boehringer Ingelheim, 3; M. Girard, Boehringer Ingelheim, 3; S. Stowasser, Boehringer Ingelheim, 3; D. Zoz, Boehringer Ingelheim, 3, Boehringer Ingelheim Pharmaceuticals, 3; A. Fischer, Boehringer Ingelheim, 5, Bristol Myers Squibb, 5, Bristol-Myers Squibb, 5, Hoffmann-La Roche, 5, Roche, 5; T. Maher, Boehringer Ingelheim, 5, 8.

To cite this abstract in AMA style:

Highland K, Distler O, Kuwana M, Allanore Y, Assassi S, Azuma A, Bourdin A, Denton C, Distler J, Hoffmann-Vold A, Khanna D, Mayes M, Raghu G, Vonk M, Gahlemann M, Girard M, Stowasser S, Zoz D, Fischer A, Maher T. Efficacy and Safety of Nintedanib in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease by Use of Mycophenolate at Baseline: Subgroup Analysis of the SENSCIS Trial [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/efficacy-and-safety-of-nintedanib-in-patients-with-systemic-sclerosis-associated-interstitial-lung-disease-by-use-of-mycophenolate-at-baseline-subgroup-analysis-of-the-senscis-trial/. Accessed .

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