Real-World Safety, Tolerability and Effectiveness of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis: Final Report of Post-marketing Surveillance in Japan

IF 3.4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Therapy Pub Date : 2024-12-23 DOI:10.1007/s12325-024-03079-2

Yoshikazu Inoue, Takashi Ogura, Arata Azuma, Yasuhiro Kondoh, Sakae Homma, Kenya Muraishi, Rie Ikeda, Kaori Ochiai, Yukihiko Sugiyama, Toshihiro Nukiwa

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Abstract

Introduction

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.

Methods

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.

Results

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).

Conclusion

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.

Study Registration

ClinicalTrials.gov (NCT02607722)/European Union electronic register of Post-Authorisation Studies (EUPAS10891).

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尼达尼布在特发性肺纤维化患者中的安全性、耐受性和有效性：日本上市后监测的最终报告

特发性肺纤维化（Idiopathic pulmonary fibrosis， IPF）是一种慢性进行性纤维化间质性肺炎，以呼吸困难和肺功能进行性恶化为特征。推荐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现实环境中评估尼达尼布治疗IPF患者超过24个月的安全性和有效性。方法：这项针对尼达尼布的前瞻性、非干预性、全病例经前综合征研究纳入了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）相对基线调整后的绝对变化。结果：共有来自1013家机构的5717例患者纳入安全性分析（平均±标准差年龄71.7±8.1岁，78.1%为男性，70.8%为吸烟者或既往吸烟者）。大多数患者（83.9%）开始服用150mg胶囊，每日两次。在24个月时，2841名患者（64.8%）停止使用尼达尼布，主要原因是不良事件（44.0%）、不良反应（24.1%）或疗效不足（5.7%）。最常见的不良反应是腹泻（35.5%）、肝功能异常（14.4%）、食欲下降（9.9%）、肝脏疾病（7.8%）和恶心（5.8%）。从基线到24个月，调整后的FVC绝对平均变化为- 212.3 mL（95%可信区间- 235.3,- 189.3）。结论：这是对接受尼达尼布治疗的IPF患者进行的最大的前瞻性研究。在日本IPF患者的现实环境中，尼达尼布治疗的安全性和有效性与之前的研究报告相似。尼达尼布有效地减缓了IPF的进展。未发现新的安全问题，并确认需要适当管理肝脏疾病和腹泻（根据批准的产品信息）。研究注册：ClinicalTrials.gov (NCT02607722)/欧盟授权后研究电子注册（EUPAS10891）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

期刊介绍： Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.