尼达尼布治疗特发性肺纤维化的真实世界安全性和耐受性：日本上市后监测的中期报告。
Real-World Safety and Tolerability of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis: Interim Report of a Post-Marketing Surveillance in Japan.
机构信息
Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-Higashi, Kanazawa-ku, Yokohama, Kanagawa, 236-0051, Japan.
Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan.
出版信息
Adv Ther. 2023 Apr;40(4):1474-1493. doi: 10.1007/s12325-022-02411-y. Epub 2023 Jan 24.
INTRODUCTION
Nintedanib is recommended for the treatment of idiopathic pulmonary fibrosis (IPF); however, treatment discontinuation due to adverse events (AEs) is common. A large-scale post-marketing surveillance study is investigating the real-world tolerability/safety of nintedanib in Japanese patients with IPF in routine clinical practice. Here, we report a 12-month interim analysis of this study.
METHODS
The study included Japanese patients with IPF who started nintedanib between 31 August 2015 and 25 December 2018. The primary outcome was the frequency of adverse drug reactions (ADRs), defined as AEs for which a causal relationship with nintedanib could not be excluded. The secondary outcome was change from baseline in forced vital capacity (FVC). Outcomes were analysed in patients who stopped ('discontinued' subgroup) and continued ('continued' subgroup) nintedanib after 12 months. A multivariate analysis was performed to determine potential risk factors for treatment discontinuation.
RESULTS
Of 5578 patients in the safety analysis set, 2795 (50.1%) discontinued nintedanib within 12 months of treatment initiation. Overall, 3767 patients (67.5%) had ADRs, with 1356 (24.3%) discontinuing nintedanib because of an ADR. Among patients in the 'discontinued' subgroup (n = 2795), 1442 (51.6%) discontinued because of an ADR. The most common ADRs causing discontinuation within 3 and 12 months were hepatic function abnormal (n = 137/730; 18.8%) and diarrhoea (n = 190/1442; 13.2%), respectively. At 12 months, the decrease in FVC from baseline was smaller in the 'continued' versus the 'discontinued' subgroup (adjusted mean ± standard error change - 104.4 ± 10.9 ml vs. - 311.2 ± 29.2 ml). Stage III/IV IPF and FVC < 70% predicted at baseline were risk factors for early treatment discontinuation.
CONCLUSION
About 50% of Japanese patients with IPF discontinued nintedanib within the first year of treatment, with worse lung function being associated with an increased risk of early treatment discontinuation.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT02607722; European Union electronic register of Post-Authorisation Studies: EUPAS10891.
简介
尼达尼布被推荐用于特发性肺纤维化（IPF）的治疗；然而，由于不良反应（AE）而停药很常见。一项大规模的上市后监测研究正在调查尼达尼布在日本 IPF 患者中的真实世界耐受性/安全性，该研究正在常规临床实践中进行。在此，我们报告了该研究的 12 个月中期分析结果。
方法
该研究纳入了 2015 年 8 月 31 日至 2018 年 12 月 25 日期间开始接受尼达尼布治疗的日本 IPF 患者。主要结局为药物不良反应（ADR）的频率，定义为与尼达尼布因果关系不能排除的不良事件。次要结局为用力肺活量（FVC）从基线的变化。在 12 个月后停止（“停药”亚组）和继续（“继续”亚组）尼达尼布治疗的患者中分析结局。进行了多变量分析以确定停药的潜在危险因素。
结果
在安全性分析集中的 5578 例患者中，有 2795 例（50.1%）在治疗开始后 12 个月内停止了尼达尼布治疗。总体而言，有 3767 例（67.5%）发生了 ADR，有 1356 例（24.3%）因 ADR 而停止了尼达尼布治疗。在“停药”亚组（n=2795）中，有 1442 例（51.6%）因 ADR 而停药。在 3 个月和 12 个月内导致停药的最常见 ADR 分别为肝功能异常（n=137/730；18.8%）和腹泻（n=190/1442；13.2%）。在 12 个月时，与“停药”亚组相比，“继续”亚组的 FVC 从基线的下降幅度较小（调整后平均变化±标准误差为-104.4±10.9 ml 与-311.2±29.2 ml）。III/IV 期 IPF 和基线时 FVC＜70%预计值是早期停药的危险因素。
结论
约 50%的日本特发性肺纤维化患者在治疗的第一年停止了尼达尼布治疗，肺功能越差，早期停药的风险越高。
临床试验注册
ClinicalTrials.gov：NCT02607722；欧盟上市后研究电子登记处：EUPAS10891。
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