Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan.
Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan.
Respir Investig. 2021 Nov;59(6):819-826. doi: 10.1016/j.resinv.2021.04.005. Epub 2021 May 14.
Phase IV clinical trials in Western countries have reported that combined therapy with pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF) has a manageable safety profile. However, data on the long-term safety and tolerability of this combination treatment in the real-world setting in Japan are limited.
The retrospective data of 46 patients with IPF who received combination therapy with pirfenidone and nintedanib were obtained from 16 institutes in Japan. Adverse events and adverse drug reactions (ADRs) were reported through a retrospective review of medical records.
Nintedanib and pirfenidone were added to preceding treatment with antifibrotic drugs in 32 (69.6%) and 13 (28.3%) patients, respectively. In one patient (2.1%), the two drugs were concurrently initiated. The mean duration of monotherapy before initiating the combination was 26.3 months. In 26 of 38 patients (68.4%), the Gender-Age-Physiology index stage was II or III. Thirty-three patients (71.7%) had some ADRs, and 14 patients (30.4%) permanently discontinued either drug or both drugs owing to the development of ADRs during the observation period (mean: 59 weeks). The percentage of grade III or IV IPF according to the Japanese Respiratory Society severity classification was higher in patients who permanently discontinued either drug or both drugs than in those who continued both drugs (90.9% [10/11; 3 undetermined grade] vs. 61.1% [11/18; 1 undetermined grade]). Decreased appetite (18/46, 39.1%) and diarrhea (16/46, 34.8%) were frequently observed ADRs. Two patients (4.3%) had serious ADRs (liver toxicity and pneumothorax).
Real-world data imply that combination therapy with pirfenidone and nintedanib for IPF has a manageable safety/tolerability profile.
在西方国家进行的 IV 期临床试验报告称，联合应用吡非尼酮和尼达尼布治疗特发性肺纤维化（IPF）具有可管理的安全性。然而，在日本的真实环境中，关于这种联合治疗的长期安全性和耐受性的数据有限。
从日本的 16 个机构获得了 46 例接受吡非尼酮和尼达尼布联合治疗的 IPF 患者的回顾性数据。通过回顾病历报告不良事件和药物不良反应（ADR）。
32 例（69.6%）和 13 例（28.3%）患者分别在抗纤维化药物治疗的基础上加用尼达尼布和吡非尼酮。1 例（2.1%）患者同时开始使用两种药物。在开始联合治疗前，单药治疗的平均持续时间为 26.3 个月。38 例患者中的 26 例（68.4%）性别-年龄-生理指数（Gender-Age-Physiology index，GAPI）分期为 II 或 III 期。33 例（71.7%）患者出现了一些 ADR，14 例（30.4%）患者因在观察期间（平均 59 周）发生 ADR 而永久停用一种或两种药物。与继续使用两种药物的患者相比，因发生 ADR 而永久停用一种或两种药物的患者中，根据日本呼吸学会（Japanese Respiratory Society，JRS）严重程度分类为 III 或 IV 级的 IPF 百分比更高（90.9%[10/11；3 例未确定等级] vs. 61.1%[11/18；1 例未确定等级]）。食欲减退（18/46，39.1%）和腹泻（16/46，34.8%）是常见的 ADR。2 例（4.3%）患者发生严重 ADR（肝毒性和气胸）。
真实世界的数据表明，吡非尼酮和尼达尼布联合治疗 IPF 具有可管理的安全性/耐受性。
