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  • Safety and tolerability of nintedanib in patients with systemic sclerosis-associated interstitial lung disease: data from the SENSCIS trial

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Systemic sclerosis
Safety and tolerability of nintedanib in patients with systemic sclerosis-associated interstitial lung disease: data from the SENSCIS trial
  1. James R Seibold1,
  2. Toby M Maher2,3,4,
  3. Kristin B Highland5,
  4. Shervin Assassi6,
  5. Arata Azuma7,
  6. Laura Kathleen Hummers8,
  7. Ulrich Costabel9,
  8. Ute von Wangenheim10,
  9. Veronika Kohlbrenner11,
  10. Martina Gahlemann12,
  11. Margarida Alves13,
  12. Oliver Distler14
  13. on behalf of the SENSCIS trial investigators
  1. 1 Scleroderma Research Consultants, LLC, Aiken, South Carolina, USA
  2. 2 National Heart and Lung Institute, Imperial College London, London, UK
  3. 3 National Institute for Health Research Clinical Research Facility, Royal Brompton Hospital, London, UK
  4. 4 Keck School of Medicine, University of Southern California, Los Angeles, California, USA
  5. 5 Respiratory Institute, Cleveland Clinic, Cleveland, Ohio, USA
  6. 6 University of Texas Houston Medical School, Houston, Texas, USA
  7. 7 Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
  8. 8 Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  9. 9 Interstitial and Rare Lung Disease Unit, Department of Pneumology, Ruhrlandklinik, University Hospital Essen, Essen, Germany
  10. 10 Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
  11. 11 Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Connecticut, USA
  12. 12 Boehringer Ingelheim (Schweiz) GmbH, Basel, Switzerland
  13. 13 Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
  14. 14 Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland
  1. Correspondence to Dr James R Seibold, Scleroderma Research Consultants, LLC, Aiken, SC 29803, USA; jamesrseibold{at}gmail.com

Abstract

Objectives To characterise the safety and tolerability of nintedanib and the dose adjustments used to manage adverse events in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD).

Methods In the SENSCIS trial, patients with SSc-ILD were randomised to receive nintedanib 150 mg two times per day or placebo. To manage adverse events, treatment could be interrupted or the dose reduced to 100 mg two times per day. We assessed adverse events and dose adjustments over 52 weeks.

Results A total of 576 patients received nintedanib (n=288) or placebo (n=288). The most common adverse event was diarrhoea, reported in 75.7% of patients in the nintedanib group and 31.6% in the placebo group; diarrhoea led to permanent treatment discontinuation in 6.9% and 0.3% of patients in the nintedanib and placebo groups, respectively. In the nintedanib and placebo groups, respectively, 48.3% and 12.2% of patients had ≥1 dose reduction and/or treatment interruption, and adverse events led to permanent discontinuation of the trial drug in 16.0% and 8.7% of patients. The adverse events associated with nintedanib were similar across subgroups defined by age, sex, race and weight. The rate of decline in forced vital capacity in patients treated with nintedanib was similar irrespective of dose adjustments.

Conclusions The adverse event profile of nintedanib in patients with SSc-ILD is consistent with its established safety and tolerability profile in patients with idiopathic pulmonary fibrosis. Dose adjustment is important to minimise the impact of adverse events and help patients remain on therapy.

  • autoimmune diseases
  • systemic sclerosis
  • pulmonary fibrosis
https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/annrheumdis-2020-217331

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    Footnotes

    • Handling editor Josef S Smolen

    • Twitter @ShervinAssassi

    • Contributors JRS, TMM, KH, SA, AA, LKH and OD were involved in data acquisition. All authors were involved in the analysis and interpretation of the data and in drafting the manuscript.

    • Funding The SENSCIS trial was funded by Boehringer Ingelheim.

    • Competing interests JRS reports personal fees from Atlantic, Bayer, Blade, Boehringer Ingelheim, Camurus, Corbus, DRG, Eicos, Eiger Pharmaceuticals, EMD Serono, Guidepoint, Indalo, Mitsubishi and Xenikos; and stock ownership or options in BriaCell and Pacific Therapeutics. TMM reports grants and personal fees from GlaxoSmithKline and UCB, and personal fees from Apellis, Bayer, Biogen Idec, Blade, Boehringer Ingelheim, Bristol-Myers Squibb, Galapagos, Galecto, Indalo, Novartis, Respivent, Roche and Trevi. KBH reports grants and personal fees from Actelion Pharmaceuticals, Boehringer Ingelheim and United Therapeutics; personal fees from Bayer; and grants from Genentech, Eiger BioPharmaceuticals and Reata Pharmaceuticals. SA reports grants, personal fees and other remuneration from Boehringer Ingelheim; grants from Bayer, Biogen Idec and Momenta; and personal fees from Medscape, Integrity Continuing Education and Corbus. AA reports personal fees and other remuneration from Boehringer Ingelheim, Taiho Pharmaceutical and Toray; personal fees from Asahi Kasei Pharma; and other remuneration from Shionogi & Co., Ltd, and aTyr Pharma. LKH reports other remuneration from Boehringer Ingelheim (investigator of SENSCIS trial). UC reports personal fees and non-financial support from Boehringer Ingelheim and Roche; and personal fees from AstraZeneca, Fibrogen, Novartis and Pliant Therapeutics. UvW, VK, MG and MA are employees of Boehringer Ingelheim. OD reports grants and personal fees from Actelion, Bayer, Boehringer Ingelheim and Mitsubishi; personal fees from AbbVie, Acceleron Pharma, Anamar, Amgen, Baecon Discovery, Blade Therapeutics, Catenion, CSL Behring, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, Glenmark Pharma, GlaxoSmithKline, Inventiva, Italfarmaco, IQVIA, Lilly, Medac, Medscape, Menarini, Mepha, Merck Sharp & Dohme, Novartis, Roche, Sanofi, Target BioScience and UCB; personal fees and non-financial support from Pfizer; and patent US8247389. TMM, KBH, AA and OD were members of the SENSCIS trial steering committee.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Patient consent for publication Not required.

    • Ethics approval The study protocol was reviewed and approved by the Independent Ethics Committees and/or Institutional Review Boards of the participating centres. Written informed consent was obtained from all patients before study entry.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available upon reasonable request (see online supplementary files).