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

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). 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. 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. 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.

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Déclaration de conflit d'intérêts

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.