Safety and Tolerability of Nintedanib in Patients with Fibrosing Interstitial Lung Diseases: Post-marketing Data

Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF), other forms of progressive pulmonary fibrosis (PPF), and systemic sclerosis-associated interstitial lung disease (ILD). We present global post-marketing safety data for nintedanib in these fibrosing ILDs. Data on adverse events in patients with fibrosing ILDs who were treated with nintedanib were collected via spontaneous reporting and solicited reporting in various studies (excluding clinical trials). Data were collected from 15 October 2014 (first regulatory approval) to 15 October 2023. Adverse events were coded using the Medical Dictionary for Regulatory Activities. Cumulative exposure to nintedanib was estimated using sales data. Cumulative exposure to nintedanib was 380,557 patient–years. Diarrhoea was reported at a rate of 227.5 per 1000 patient–years. Only 2.6% of diarrhoea events were reported as serious. Of 39,788 (33.6%) diarrhoea events with a known time to onset, almost 60% occurred within the first 3 months of treatment. The rate of serious liver enzyme and bilirubin elevations (including drug-induced liver injury) was 4.0 per 1000 patient–years. Bleeding was reported at a rate of 24.2 per 1000 patient–years. Most (81.3%) bleeding events were non-serious. The rates of myocardial infarction, ischaemic stroke, and venous thromboembolism were 3.3, 3.3, and 2.0 per 1000 patient–years, respectively. Gastrointestinal perforation was reported at a rate of 0.9 per 1000 patient–years. Post-marketing safety data on established and potential adverse events associated with nintedanib in patients with fibrosing ILDs, collected over 9 years, demonstrated a safety profile that was similar to that established in clinical trials and provided in the product labels. Education of patients about the adverse events that may be associated with nintedanib, and the effective management of adverse events when they occur, is important to minimise the impact of adverse events and help patients remain on treatment. Nintedanib is a drug that is used to treat interstitial lung diseases (ILDs) that lead to fibrosis (scarring) of the lungs. The results of clinical trials showed that the most frequent adverse events seen in patients treated with nintedanib are gastrointestinal events, particularly diarrhoea. This analysis looked at safety data from patients with ILDs treated with nintedanib. Data were collected from the time that nintedanib was approved for the treatment of ILDs (15 October 2014) to 15 October 2023. The findings showed that the safety profile of nintedanib in the real world was similar to that seen in clinical trials. Diarrhoea was the most frequent adverse event reported, but was only regarded as serious in about 1 in 38 events. It is important that clinicians using nintedanib to treat ILDs educate patients about the adverse events that may occur and how to manage them.