Tezepelumab治疗加拿大成人严重慢性鼻窦炎伴鼻息肉：3期WAYPOINT试验的亚组分析

文献信息

中文摘要

重要性： Tezepelumab是一种靶向胸腺基质淋巴细胞生成素的单克隆抗体，近期在加拿大获批用于治疗严重未控制的慢性鼻窦炎伴鼻息肉（CRSwNP）。其在加拿大具体环境中的有效性尚未得到评估。
目的： 分析入组WAYPOINT试验的加拿大患者中Tezepelumab的疗效和安全性，并结合加拿大医疗环境对结果进行解读。
设计： 一项多国、平行组、随机、安慰剂对照3期试验的事后分析。
参与者： 49例加拿大成人严重未控制CRSwNP患者。
地点： 入组WAYPOINT试验的加拿大患者亚组。
干预： Tezepelumab 210 mg（n=25）或安慰剂（n=24），每4周皮下给药一次，持续52周。
主要结局指标： 共同主要终点为从基线至第52周的内镜下鼻息肉总分（NPS）变化和患者报告的每两周鼻塞评分（NCS）变化。
结果： 与完整研究人群相比，加拿大队列中哮喘和非甾体抗炎药加重性呼吸系统疾病患者数量更多。在加拿大队列中，与安慰剂相比，Tezepelumab显著改善了CRSwNP的客观和主观体征与症状，包括两个共同主要终点（与安慰剂相比的最小二乘均值差[95%置信区间]：NPS总分，-2.53[-3.33至-1.73]，P<.0001；平均NCS，-1.10[-1.62至-0.58]，P<.0001）以及总体人群中的所有次要疗效终点。加拿大队列与完整研究人群的临床获益幅度相似，与安慰剂相比，补救治疗（鼻息肉手术和/或全身性糖皮质激素）使用频率更低。Tezepelumab的安全性特征在加拿大队列中与完整研究人群一致。加拿大队列中未发生严重不良事件（AE），也无因AE而停药的情况。
结论： Tezepelumab对于反映加拿大临床实际情况的患者人群中严重未控制CRSwNP是一种有效且安全的治疗。
相关性： 多国WAYPOINT试验结果与加拿大临床实践中常规见到的CRSwNP患者相关，支持其在加拿大医疗环境中的适用性。
试验注册： WAYPOINT ClinicalTrials.gov编号，NCT04851964。

英文摘要

IMPORTANCE: Tezepelumab, a monoclonal antibody targeted against thymic stromal lymphopoietin, was recently approved in Canada for the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). Its effectiveness specifically in the Canadian setting has not been evaluated.
OBJECTIVE: To analyze the efficacy and safety of tezepelumab in Canadian patients enrolled in the WAYPOINT trial and contextualize the findings with respect to the Canadian healthcare environment.
DESIGN: Post hoc analysis of a multinational, parallel-group, randomized, placebo-controlled, Phase 3 trial.
PARTICIPANTS: Forty-nine Canadian adult patients with severe uncontrolled CRSwNP.
SETTING: Subgroup of Canadian patients enrolled in the WAYPOINT trial.
INTERVENTION: Tezepelumab 210 mg (n = 25) or placebo (n = 24) administered subcutaneously every 4 weeks for 52 weeks.
MAIN OUTCOME MEASURES: The co-primary endpoints were change from baseline to week 52 in endoscopic total nasal polyp score (NPS) and patient-reported bi-weekly nasal congestion score (NCS).
RESULTS: The Canadian cohort had higher numbers of patients with asthma and nonsteroidal anti-inflammatory drug-exacerbated respiratory disease than in the full study population. Objective and subjective signs and symptoms of CRSwNP were significantly improved with tezepelumab compared with placebo in the Canadian cohort, including both co-primary endpoints (least squares mean difference vs placebo [95% confidence interval]: total NPS, -2.53 [-3.33 to -1.73], P < .0001; mean NCS, -1.10 [-1.62 to -0.58], P < .0001) and all secondary efficacy endpoints in the overall population. The magnitude of clinical benefit was similar in the Canadian cohort versus the full study population, with less frequent use of rescue therapy (nasal polyp surgery and/or systemic corticosteroids) compared to placebo. The safety profile of tezepelumab was consistent in the Canadian cohort as in the full study population. There were no serious adverse events (AEs) or discontinuations due to AEs in the Canadian cohort.
CONCLUSIONS: Tezepelumab is an effective and safe treatment for severe uncontrolled CRSwNP in a patient population that is reflective of the Canadian clinical landscape.
RELEVANCE: The multinational WAYPOINT trial findings are relevant to patients with CRSwNP routinely seen in Canadian clinical practice, supporting their applicability in the Canadian healthcare context.
TRIAL REGISTRY: WAYPOINT ClinicalTrials.gov number, NCT04851964.