Department of Respiratory Diseases, Akdeniz University, Antalya, Turkey.
Department of Respiratory Diseases, Akdeniz University, Antalya, Turkey.
Pulm Pharmacol Ther. 2021 Dec;71:102099. doi: 10.1016/j.pupt.2021.102099. Epub 2021 Nov 15.
The antifibrotic drugs nintedanib and pirfenidone reduce disease progression in idiopathic pulmonary fibrosis (IPF) and have also shown to improve survival. Switching first-line antifibrotic drug may required in IPF due to disease progression or intolerable adverse effects. The aim of this study was to assess the safety and efficacy of second-line antifibrotic treatment in patients with IPF.
This retrospective, multicenter study was conducted at three referral interstitial lung disease centers who received first-line antifibrotics more than one month and switched the treatment to a second-line antifibrotic agent during January 2016-June 2021. The drug's safety was evaluated based on the type of adverse effect. Disease progression was defined as an absolute decline in FVC of >10% within 12 months with or without radiological progression.
Among 629 consecutive patients with IPF, 66 patients switched antifibrotics. The median duration of antifibrotics was 13 (1-41) months prior to the switch, and 14 (2-42) months after the switch. The mean age was 70.6 ± 8.9 years and, median FVC (%) was 72.1 ± 18.7 at the initiation of first-line antifibrotics. The most common reason for the switch was disease progression (56%) followed by severe adverse effects (SAEs) (44%). SAEs were significantly less observed after the switch compared before the switch (43.9% vs12.1%, respectively, p < 0.001). Eighteen patients had adverse effects due to second-line antifibrotics. Among these patients, 10 had mild adverse effects and 8 had severe adverse effects. While there was no change in the FVC (%) values in 30.3% patients 12 months after the first-line antifibrotic treatment (before the switch), there was no change in the FVC (%) values in 40% patients at the end of 12 months after the switch. Fourteen patients (42.4%) who received antifibrotic treatment before the switch had more than 10% decline in FVC (%) at the end of 12 months. Eight patients (32.0%) had 10% or more decline in FVC (%) 12 months after the switch.
Patients with IPF who do not tolerate first-line antifibrotic treatment or those showing disease progression despite treatment, switching antifibrotics may be a feasible management strategy.
尼达尼布和吡非尼酮这两种抗纤维化药物可减缓特发性肺纤维化（IPF）的疾病进展，并且已显示出可改善生存率。由于疾病进展或无法耐受的不良反应，可能需要在 IPF 患者中更换一线抗纤维化药物。本研究旨在评估 IPF 患者二线抗纤维化治疗的安全性和疗效。
这是一项回顾性、多中心研究，在三家转诊间质性肺病中心进行，这些中心在 2016 年 1 月至 2021 年 6 月期间接受了一线抗纤维化药物治疗超过一个月，并在该期间将治疗方案转换为二线抗纤维化药物。药物安全性基于不良反应的类型进行评估。疾病进展定义为 12 个月内 FVC 绝对值下降>10%，无论是否存在影像学进展。
在 629 例连续的 IPF 患者中，有 66 例患者更换了抗纤维化药物。在转换前，一线抗纤维化药物的中位持续时间为 13（1-41）个月，转换后为 14（2-42）个月。起始一线抗纤维化药物时的平均年龄为 70.6±8.9 岁，中位 FVC（%）为 72.1±18.7。更换药物的最常见原因是疾病进展（56%），其次是严重不良反应（SAEs）（44%）。与转换前相比，转换后 SAE 明显减少（分别为 43.9%和 12.1%，p<0.001）。18 例患者因二线抗纤维化药物出现不良反应。这些患者中，10 例为轻度不良反应，8 例为重度不良反应。在一线抗纤维化治疗 12 个月后（转换前），30.3%的患者 FVC（%）值无变化，而在转换后 12 个月结束时，40%的患者 FVC（%）值无变化。在转换前接受抗纤维化治疗的 14 例患者（42.4%）在 12 个月结束时 FVC（%）下降超过 10%。在转换后 12 个月时，8 例患者（32.0%）FVC（%）下降 10%或更多。
对于不能耐受一线抗纤维化治疗的 IPF 患者或尽管接受治疗仍有疾病进展的患者，更换抗纤维化药物可能是一种可行的治疗策略。
