美国华盛顿大学Ganesh Raghu团队研究了潘瑞鲁单抗治疗特发性肺纤维化的疗效和安全性。2024年5月19日，《美国医学会杂志》发表了这一成果。

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，潘瑞鲁单抗（一种与结缔组织生长因子活性结合并抑制其活性的全人源单克隆抗体）减轻了特发性肺纤维化的进展，没有出现实质性不良事件。该研究旨在评估潘瑞鲁单抗治疗特发性肺纤维化的疗效和安全性。

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尼达尼布或吡非尼酮的抗纤维化治疗。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。将参与者随机分组，分别接受潘瑞鲁单抗（每3周静脉注射30 mg/kg；n = 181）或安慰剂（n = 175）治疗48周。主要结局为从基线到第48周用力肺活量（FVC）的绝对变化。有5种次要结局（包括疾病进展时间，定义为预测FVC或死亡下降≥10%）。探索性结局包括患者报告的症状。还报告了不良事件。

356名患者（平均年龄70.5岁；258名[72.5%]为男性；221名[62.1%]为白人）中，277名（77.8%）完成了试验。从基线到第48周，FVC的绝对变化在组间没有显著差异（潘瑞鲁单抗组的最小二乘平均值为−260 mL[95%CI，−350至−170 mL]，安慰剂组为−330 mL[95%置信区间，−430至−230 mL]；组间平均差为70 mL[95%可信区间，−60至190 mL]，P =0 .29）。 在任何次要结局或患者报告的结局方面，组间无显著差异。在潘瑞鲁单抗组中，有160名患者（88.4%）发生治疗相关不良事件，51名患者（28.2%）发生严重不良事件，而安慰剂组中分别为151名（86.3%）和60名（34.3%）。在研究期间，每组有23名患者死亡（潘瑞鲁单抗组为12.7%，安慰剂组为13.1%）。

研究结果表明，在接受潘瑞鲁单抗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绝对变化的主要结局在组间没有统计学显著差异。

附：英文原文

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

Author: Ganesh Raghu, Luca Richeldi, Evans R. Fernández Pérez, Maria Cristina De Salvo, Rafael S. Silva, Jin Woo Song, Takashi Ogura, Zuo Jun Xu, Elizabeth A. Belloli, Xueping Zhang, Lorilyn L. Seid, Lona Poole, ZEPHYRUS- Study Investigators, Simon Bowler, Tamera Corte, Mark Holmes, Francis Thien, John Wheatley, Sun-Mi Choi, Man-Pyo Chung, Sunghwan Jeong, Yonghyun Kim, Eun-Joo Lee, Hyun-Kyung Lee, Choonsik Park, Jong Sun Park, Joo Hun Park, David Chi-Leung Lam, Ming-Cheng Chan, Kang-Yun Lee, Jie Cao, Juan Chen, Rongchang Chen, Huaping Dai, Xiuhua Fu, Zongan Liang, Qun Luo, Guochao Shi, Zhaohui Tong, Limin Wang, Shuanying Yang, Hongtao Yu, Huilan Zhang, Jianchu Zhang, Hui Zhao, Wei Wang, Ying Meng, Hong Peng, Murali Ramaswamy, Mark Hamblin, John Fitzgerald, Nishant Gupta, Jane Dematte, Srihari Veeraraghavan, Thomas O’Brien, Tracy Luckhardt, Lisa Lancaster, Marta Kokoszynska, Neil Ettinger, Thomas D. Kaelin, Ather Siddiqi, Bridget Collins, Mary Beth Scholand, Danielle Antin-Ozerkis, Kim Hyun, Christopher Harden, Frank Averill, Jorge Mallea, Rebecca Bascom, Vandana Seeram, Amy Hajari Case, Edward Britt, Barry Shea, Gerard Criner, Mark Gotfried, Yolanda Mageto

Issue&Volume: 2024-05-19

Abstract:

Importance  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.

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

Design, Setting, and Participants  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.

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

Main Outcomes and Measures  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.

Results  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).

Conclusions and Relevance  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.

DOI: 10.1001/jama.2024.8693

Source: https://jamanetwork.com/journals/jama/fullarticle/2819084