Inoue Yoshikazu, Ogura Takashi, Azuma Arata, Kondoh Yasuhiro, Homma Sakae, Muraishi Kenya, Ikeda Rie, Ochiai Kaori, Sugiyama Yukihiko, Nukiwa Toshihiro
Osaka Anti-Tuberculosis Association, Osaka Fukujuji Hospital, Osaka, Japan.
Clinical Research Center, NHO Kinki Chuo Chest Medical Center, 1180 Nagasone-Cho, Kita-Ku, Sakai, Osaka, 591-8555, Japan.
Adv Ther. 2025 Feb;42(2):1075-1093. doi: 10.1007/s12325-024-03079-2. Epub 2024 Dec 23.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial pneumonia, which is characterised by progressive worsening of dyspnoea and lung function. Nintedanib treatment is recommended to slow IPF disease progression. The aim of this post-marketing surveillance (PMS) study was to evaluate the safety and effectiveness of nintedanib over 24 months in patients with IPF in a real-world setting in Japan.
This prospective, non-interventional, all-case PMS study of nintedanib included Japanese patients with IPF who started nintedanib between 7 October 2015 and 2 May 2023. The primary outcome was to determine the proportion of patients with adverse drug reactions (ADRs), and the secondary outcome was the adjusted absolute change from baseline in forced vital capacity (FVC) at 24 months.
In total, 5717 patients from 1013 institutions were included in the safety analysis (mean ± standard deviation age 71.7 ± 8.1 years, 78.1% male, 70.8% current or former smokers). Most patients (83.9%) had initiated nintedanib at a dose of 150 mg capsules twice daily. At 24 months, 2841 patients (64.8%) had discontinued nintedanib, mainly due to adverse events (44.0%), ADRs (24.1%) or insufficient effectiveness (5.7%). The most common ADRs were diarrhoea (35.5%), hepatic function abnormal (14.4%), decreased appetite (9.9%), liver disorders (7.8%) and nausea (5.8%). The adjusted absolute mean change in FVC from baseline to 24 months was - 212.3 mL (95% confidence interval - 235.3, - 189.3).
This is the largest prospective study to investigate patients with IPF who were treated with nintedanib. The safety and effectiveness of nintedanib treatment in this real-world setting of Japanese patients with IPF was similar to that reported in previous studies. Nintedanib effectively slowed the progression of IPF. No new safety concerns were identified, and the need for appropriate management of hepatic disorders and diarrhoea (as per the approved product information) was confirmed.
ClinicalTrials.gov (NCT02607722)/European Union electronic register of Post-Authorisation Studies (EUPAS10891).
特发性肺纤维化（IPF）是一种慢性、进行性、纤维化间质性肺炎，其特征为呼吸困难和肺功能进行性恶化。推荐使用尼达尼布治疗以减缓IPF疾病进展。这项上市后监测（PMS）研究的目的是在日本的实际临床环境中评估尼达尼布在24个月内对IPF患者的安全性和有效性。
这项关于尼达尼布的前瞻性、非干预性、全病例PMS研究纳入了2015年10月7日至2023年5月2日期间开始使用尼达尼布的日本IPF患者。主要结局是确定发生药物不良反应（ADR）的患者比例，次要结局是24个月时用力肺活量（FVC）相对于基线的校正后绝对变化。
安全性分析共纳入了来自1013家机构的5717例患者（平均年龄±标准差为71.7±8.1岁，男性占78.1%，当前或既往吸烟者占70.8%）。大多数患者（83.9%）开始使用的尼达尼布剂量为每日两次，每次150mg胶囊。在24个月时，2841例患者（64.8%）停用了尼达尼布，主要原因是不良事件（44.0%）、ADR（24.1%）或疗效不佳（5.7%）。最常见的ADR为腹泻（35.5%）、肝功能异常（14.4%）、食欲减退（9.9%）、肝脏疾病（7.8%）和恶心（5.8%）。FVC从基线到24个月的校正后绝对平均变化为-212.3mL（95%置信区间为-235.3，-189.3）。
这是调查接受尼达尼布治疗的IPF患者的最大规模前瞻性研究。在日本IPF患者的这一实际临床环境中，尼达尼布治疗的安全性和有效性与既往研究报道相似。尼达尼布有效减缓了IPF的进展。未发现新的安全问题，并确认了按照批准的产品信息对肝脏疾病和腹泻进行适当管理的必要性。
ClinicalTrials.gov（NCT02607722）/欧盟上市后研究电子注册库（EUPAS10891）。
