Department of Life and Health Sciences, School of Medicine, Ulster University, Northland Road, Derry-Londonderry, BT48 7JL, UK.
Pulmonary Medicine and Oncology, Nippon Medical School, Tokyo, Japan.
Adv Ther. 2024 Dec;41(12):4581-4590. doi: 10.1007/s12325-024-03023-4. Epub 2024 Oct 28.
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.
尼达尼布已获批准用于治疗特发性肺纤维化（IPF）、其他类型的进行性肺纤维化（PPF）和系统性硬化症相关间质性肺病（ILD）。我们报告了尼达尼布在这些纤维性ILD 中的全球上市后安全性数据。
通过各种研究（不包括临床试验）中的自发报告和征集报告，收集了接受尼达尼布治疗的纤维性ILD 患者的不良事件数据。数据收集自 2014 年 10 月 15 日（首次监管批准）至 2023 年 10 月 15 日。使用监管活动医学词典对不良事件进行编码。使用销售数据估计尼达尼布的累积暴露量。
尼达尼布的累积暴露量为 380,557 患者年。腹泻的报告率为每 1000 患者年 227.5 例。仅 2.6%的腹泻事件报告为严重。在 39,788 例（33.6%）已知发病时间的腹泻事件中，近 60%发生在治疗的前 3 个月内。严重肝酶和胆红素升高（包括药物性肝损伤）的发生率为每 1000 患者年 4.0 例。出血的报告率为每 1000 患者年 24.2 例。大多数（81.3%）出血事件为非严重。心肌梗死、缺血性中风和静脉血栓栓塞的发生率分别为每 1000 患者年 3.3、3.3 和 2.0 例。胃肠道穿孔的报告率为每 1000 患者年 0.9 例。
在 9 年多的时间里，收集了尼达尼布在纤维性ILD 患者中与已确定和潜在不良事件相关的上市后安全性数据，这些数据表明，其安全性与临床试验中确定的以及产品标签中提供的安全性一致。向患者教育可能与尼达尼布相关的不良事件，并在发生不良事件时进行有效管理，对于减轻不良事件的影响和帮助患者继续治疗非常重要。
