SCI

9 June 2024

Pamrevlumab for Idiopathic Pulmonary Fibrosis: The ZEPHYRUS-1 Randomized Clinical Trial

（JAMA; if=16.9）

  • Raghu G, Richeldi L, Fernández Pérez ER, De Salvo MC, Silva RS, Song JW, Ogura T, Xu ZJ, Belloli EA, Zhang X, Seid LL, Poole L

  • Respondence: graghu@uw.edu 

Importance 重要性

Current treatments for idiopathic pulmonary fibrosis slow the rate of lung function decline, but may be associated with adverse events that affect medication adherence. In phase 2 trials, pamrevlumab (a fully human monoclonal antibody that binds to and inhibits connective tissue growth factor activity) attenuated the progression of idiopathic pulmonary fibrosis without substantial adverse events.

目前特发性肺纤维化的治疗可以减缓肺功能下降的速度，但可能与影响药物依从性的不良事件有关。在2期试验中，pamrevlumab（一种与结缔组织生长因子活性结合并抑制其活性的全人类单克隆抗体）减轻了特发性肺纤维化的进展，没有出现实质性不良事件。

 

Objective 目的

To assess the efficacy and safety of pamrevlumab for patients with idiopathic pulmonary fibrosis.

评估pamrevlumab治疗特发性肺纤维化患者的疗效和安全性。

 

Design, setting, and participants 设计和参与者

Phase 3 randomized clinical trial including 356 patients aged 40 to 85 years with idiopathic pulmonary fibrosis who were not receiving antifibrotic treatment with nintedanib or pirfenidone at enrollment. Patients were recruited from 117 sites in 9 countries between July 18, 2019, and July 29, 2022; the last follow-up encounter occurred on August 28, 2023.

3期随机临床试验，包括356名年龄在40至85岁的特发性肺纤维化患者，这些患者在入组时未接受nintedanib或pirfenidone的抗纤维化治疗。患者于2019年7月18日至2022年7月29日期间从9个国家的117个地点招募；最后一次随访发生在2023年8月28日。

 

Interventions 干预

Pamrevlumab (30 mg/kg administered intravenously every 3 weeks; n = 181) or placebo (n = 175) for 48 weeks.

Pamrevlumab（每3周静脉注射30 mg/kg；n=181）或安慰剂（n=175）48周。

 

Main outcomes and measures 主要结果和指标

The primary outcome was absolute change in forced vital capacity (FVC) from baseline to week 48. There were 5 secondary outcomes (including time to disease progression, which was defined as a decline of ≥10% in predicted FVC or death). The exploratory outcomes included patient-reported symptoms. Adverse events were reported.

主要研究结果为从基线到第48周期FVC的绝对变化。共有 5 项次要结果（包括疾病进展时间，即预测 FVC 下降≥10% 或死亡）。探索性结果包括患者报告的症状，并报告了不良事件。

 

Results 结果

Among 356 patients (mean age, 70.5 years; 258 [72.5%] were men; 221 [62.1%] were White), 277 (77.8%) completed the trial. There was no significant between-group difference for absolute change in FVC from baseline to week 48 (least-squares mean, -260 mL [95% CI, -350 to -170 mL] in the pamrevlumab group vs -330 mL [95% CI, -430 to -230 mL] in the placebo group; mean between-group difference, 70 mL [95% CI, -60 to 190 mL], P = .29). There were no significant between-group differences in any of the secondary outcomes or in the patient-reported outcomes. In the pamrevlumab group, there were 160 patients (88.4%) with treatment-related adverse events and 51 patients (28.2%) with serious adverse events vs 151 (86.3%) and 60 (34.3%), respectively, in the placebo group. During the study, 23 patients died in each group (12.7% in the pamrevlumab group vs 13.1% in the placebo group).

在 356 名患者（平均年龄 70.5 岁；男性 258 人 [72.5%]；白人 221 人 [62.1%]）中，有 277 人（77.8%）完成了试验。从基线到第48周，FVC的绝对变化无明显组间差异（最小二乘法平均值，pamrevlumab组为-260 mL [95% CI, -350 to -170 mL]，安慰剂组为-330 mL [95% CI, -430 to -230 mL]；平均组间差异为70 mL [95% CI, -60 to 190 mL]，P = .29）。任何次要结果或患者报告结果均无明显组间差异。pamrevlumab组有160名患者（88.4%）出现治疗相关不良事件，51名患者（28.2%）出现严重不良事件，而安慰剂组分别有151名患者（86.3%）和60名患者（34.3%）出现严重不良事件。研究期间，两组各有23名患者死亡（pamrevlumab组为12.7%，安慰剂组为13.1%）。

 

Conclusions and relevance 结论和相关性

Among patients with idiopathic pulmonary fibrosis treated with pamrevlumab or placebo, there was no statistically significant between-group difference for the primary outcome of absolute change in FVC from baseline to week 48.

在接受pamrevlumab或安慰剂治疗的特发性肺纤维化患者中，从基线到第48周，FVC绝对变化的主要结果在组间没有统计学意义的差异。