Therapeutic Research

Abstract

Background：Nintedanib, an oral anti‒fibrotic agent, was approved for treatment of systemic sclerosis‒associated interstitial lung disease（SSc‒ILD）in Japan in December 2019.　　Objective：To evaluate the safety and tolerability of nintedanib in routine clinical practice in Japan.　　Methods：This prospective, non‒interventional, post‒marketing surveillance of nintedanib began on 15 April 2020（ClinicalTrials.gov：NCT04325217）. The primary endpoint is the incidence of adverse drug reactions（ADRs）（i.e., adverse events［AEs］to which nintedanib has a possible causal relationship）. Other outcomes include the incidence of serious AEs. We analyzed safety data for patients who received≧1 dose of nintedanib and had≧1 post‒baseline visit（safety analysis set）with 12‒week case reports by 15 October 2022 　　Results：The safety analysis set comprised 181 patients, 137（75.69％）female. Mean baseline age, body mass index, SSc‒ILD duration, and forced vital capacity were 64.0 years, 21.78 kg/m2, 5.03 years, and 2045.8 mL, respectively. Most patients began treatment with the approved dosages of 150 mg（41.99％）or 100 mg twice daily（33.70％）, mean/median treatment duration was 225/148 days. ADRs occurred in 96 patients （53.04％）, mostly commonly diarrhoea（n＝56, 30.94％）, abnormal hepatic function（n＝21, 11.60％）, and nausea（n＝18, 9.94％）. Serious AEs were reported in 21 patients （11.60％）, including serious ADRs of abnormal hepatic function（n＝2）, nephrotic syndrome, decreased appetite, drug‒induced liver injury, and hepatic enzyme increased（n＝1 each）. All serious ADRs resolved.　　Conclusion：In this interim analysis, the safety profile of nintedanib in SSc‒ILD nintepatients in routine clinical practice in Japan was consistent with previous studies, with no new concerns.