Nintedanib: New indication for systemic sclerosis-associated interstitial lung disease

Abstract

Nintedanib (Ofev™), an oral triple kinase inhibitor targeting pro-fibrotic pathways, has been used for treatment of idiopathic pulmonary fibrosis (IPF). Based on positive results from phase III, placebo-controlled, randomized comparative clinical trial conducted in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), nintedanib received marketing approval in the United States and Japan for the treatment of SSc-ILD. Nintedanib significantly reduced the annual rate of decline in forced vital capacity over 52 weeks compared with placebo. The safety profiles observed in this trial were consistent with those reported in IPF patients, and the most common adverse events were gastrointestinal disorders, including diarrhea, nausea, and vomiting, which sometimes lead to discontinuation or permanent dose reduction of nintedanib. In contrast, serious adverse events were infrequent and were related mostly to worsening of cardiopulmonary involvement of SSc. This review summarizes the milestones in development of nintedanib leading to the approval for the treatment of SSc-ILD, and covers mechanisms of action, efficacy results and safety profiles, and future perspectives of nintedanib.

Keywords:

• Interstitial lung diseases
• lung function
• nintedanib
• scleroderma
• systemic sclerosis

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Conflicts of interest

M.K. has received research grants from Actelion, and consulting fees from Bayer, Boehringer-Ingelheim, Chugai, Corbus, Galapagos, GlaxoSmithKline, and CSL Behring, and serves on the speaker bureaus for Actelion, Boehringer-Ingelheim, and Chugai.

A.A. has received research grants from Boehringer-Ingelheim, Shionogi, GlaxoSmithKline, aTyr Pharma, Norbel Pharma, Abbie, and Taiho, and consulting fees from Toray, Asahikasei, Kowa, Kyorin, and Nippon Kayaku.