Nintedanib in patients with systemic sclerosis-associated interstitial lung disease: A Japanese population analysis of the SENSCIS trial

Abstract

Objective: We examined the efficacy and safety of nintedanib in Japanese patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) in the global Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) trial. Methods: Randomised patients received oral nintedanib 150 mg (N ¼ 34) twice daily or placebo (N ¼ 36) until the last patient reached 52 weeks of treatment (up to 100 weeks). Data were analysed using a subgroup analysis model with Japanese and non-Japanese patients as subgroup variables. Results: In Japanese patients, the adjusted annual rate of forced vital capacity (FVC) decline over 52 weeks was-86.2 mL/year (nintedanib) and-90.9 mL/year (placebo); treatment difference, 4.67 mL/year (95% confidence interval, À103.28, 112.63). Treatment effect heterogeneity between Japanese and non-Japanese patients was not detected (treatment-by-visit-by-subgroup interaction; p ¼ .49). FVC decline was smaller for nintedanib versus placebo through 100 weeks in Japanese patients. The most commonly reported adverse events with nintedanib were gastrointestinal and liver disorder events; most were mild-to-moderate in severity. Conclusion: In both Japanese and non-Japanese patients with SSc-ILD, nintedanib slowed the progression of ILD, with no heterogeneity detected between the subgroups. The safety profile for nintedanib in Japanese patients was similar to that observed in patients with idiopathic pulmonary fibrosis (ClinicalTrials.gov: NCT02597933).

Efficacy and safety of nintedanib in Japanese patients with progressive fibrosing interstitial lung diseases: Subgroup analysis of the randomised, double-blind, placebo-controlled, phase 3 INBUILD trial

“…Trends towards lower risks of clinically meaningful outcomes, including acute exacerbation or death, were also observed. Although some AEs J o u r n a l P r e -p r o o f occurred more frequently compared with the overall INBUILD population, the safety profile of nintedanib was consistent with Japanese patients in previous trials of patients with IPF [28] and SSc-ILD [15].…”

“…This publication extends the analysis of Japanese patients with IPF [28] and SSc-ILD [15], and presents findings in Japanese patients with progressive fibrosing ILDs other than IPF. In Japanese patients, the efficacy and safety of nintedanib were consistent with the effects observed in the overall INBUILD population [16,17].…”

“…Although progressive fibrosing ILDs can have different aetiologies, they share similar pathophysiological mechanisms in fibrotic remodelling commonalities during clinical courses, which suggests that treatments for IPF may be of benefit for patients with other progressive fibrosing ILDs [2,8,9]. Nintedanib, a small molecule inhibitor of selected tyrosine kinases [10,11], is approved for treatment of IPF based on results of the INPULSIS and TOMORROW trials [12,13], for systemic sclerosis-associated ILD (SSc-ILD) based on the results of the SENSCIS trial [4,14,15], and for progressive fibrosing ILD based on the results of the INBUILD trial [16,17]. In the multinational INBUILD phase 3 trial [16,17], the efficacy of nintedanib in patients with progressive fibrosing ILDs (excluding IPF) was confirmed by a significant reduction in the annual rate of decline in forced vital capacity (FVC, primary endpoint) compared with placebo, independent of the fibrotic pattern on high-resolution computed tomography (HRCT) [17].…”

Spontaneous pneumothorax during nintedanib therapy in patients with systemic sclerosis‐associated interstitial lung disease

“…There were no reports on protracted wound healing in the nintedanib group of the SENSCIS study, and there was no difference in the occurrence of skin ulcers as an adverse event between the nintedanib and placebo groups (18.4% and 17.4%, respectively) [5]. However, a Japanese subgroup analysis of the SENSCIS revealed a trend towards increased prevalence of digital ulcers in the nintedanib than in the placebo group [12]. There may be racial differences in impaired wound healing with nintedanib.…”

Drugs that act on the respiratory tract

“…Pirfenidone has been studied as a perioperative therapy in patients undergoing surgical resection of primary lung cancer ( Kanayama et al, 2020 [c]), as well as a maintenance therapy in patients with unclassifiable progressive fibrosing interstitial lung disease ( Maher et al, 2020 [C]) and systemic sclerosis-related interstitial lung disease ( Acharya et al, 2020 [c]). Nintedanib use has been reported in progressive interstitial lung disease ( Wells et al, 2020 [C]), non-small cell lung cancer with IPF ( Shiratori et al, 2020 [A]), idiopathic-inflammatory-myopathy-related interstitial lung disease ( Liang et al, 2021 [c]), rheumatoid arthritis-related interstitial lung disease ( Narváez et al, 2020 [A]; Vacchi et al, 2020 [A]), systemic sclerosis-related interstitial lung disease ( Azuma et al, 2021 [C]; Bournia et al, 2021 [R]; Highland et al, 2021 [C]; Kuwana et al, 2021 [c]; Seibold et al, 2020 [C]), bronchiolitis obliterans syndrome after allogenic haematopoietic stem cell transplantation ( Tang et al, 2020 [A]), and for pulmonary fibrosis after coronavirus disease 2019 ( Ogata et al, 2021 [A]). The incidence, type, and severity of nintendanib and pirfenidone associated adverse events in these reports is consistent with what has been previously reported for these agents in clinical trials for IPF.…”