英国皇家布朗普顿医院Andrew Menzies-Gow团队研究了tezepelumab治疗成人和青少年严重、不受控制哮喘的疗效。2021年5月12日，该成果发表在《新英格兰医学杂志》上。

Tezepelumab是一种人源性单克隆抗体，可阻断胸腺基质淋巴细胞生成素，这是一种上皮细胞衍生的细胞因子，与哮喘的发病机制有关。Tezepelumab治疗严重、不受控制的哮喘患者的疗效和安全性需要进一步评估。

研究组进行了一项临床3期、多中心、随机、双盲、安慰剂对照试验，招募了1061名12-80岁严重、不受控制的哮喘患者，将其随机分组，其中529名接受tezepelumab治疗，532名接受安慰剂治疗，为期52周。主要终点是52周内哮喘恶化的年化率。次要终点包括1秒用力呼气量（FEV1）和哮喘控制问卷-6（ACQ-6）、哮喘生活质量问卷（AQLQ）、以及哮喘症状日志（ASD）。

Tezepelumab组哮喘加重的年化率为0.93，显著低于安慰剂组（2.10）。在血液嗜酸性粒细胞计数低于每微升300个细胞的患者中，tezepelumab组的年化率为1.02，仍显著低于安慰剂组（1.73）。在第52周时，tezepelumab对支气管扩张前FEV1、ACQ-6评分、AQLQ和ASD的改善均优于安慰剂。两组不良事件的发生率和类型无明显差异。

研究结果表明，对于严重、不受控制的哮喘患者，采用tezepelumab治疗，与安慰剂组相比，哮喘恶化更少，患者的肺功能、哮喘控制和健康相关生活质量更好。

附：英文原文

Title: Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma

Author: Andrew Menzies-Gow, M.D.,, Jonathan Corren, M.D.,, Arnaud Bourdin, M.D.,, Geoffrey Chupp, M.D.,, Elliot Israel, M.D.,, Michael E. Wechsler, M.D.,, Christopher E. Brightling, F.Med.Sci.,, Janet M. Griffiths, Ph.D.,, sa Hellqvist, M.Sc.,, Karin Bowen, M.Sc.,, Primal Kaur, M.D.,, Gun Almqvist, M.Sc.,, Sandhia Ponnarambil, M.D.,, and Gene Colice, M.D.

Issue&Volume: 2021-05-12

Abstract:

Background

Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial-cell–derived cytokine implicated in the pathogenesis of asthma. The efficacy and safety of tezepelumab in patients with severe, uncontrolled asthma require further assessment.

Methods

We conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Patients (12 to 80 years of age) were randomly assigned to receive tezepelumab (210 mg) or placebo subcutaneously every 4 weeks for 52 weeks. The primary end point was the annualized rate of asthma exacerbations over a period of 52 weeks. This end point was also assessed in patients with baseline blood eosinophil counts of less than 300 cells per microliter. Secondary end points included the forced expiratory volume in 1 second (FEV1) and scores on the Asthma Control Questionnaire–6 (ACQ-6; range, 0 [no impairment] to 6 [maximum impairment]), Asthma Quality of Life Questionnaire (AQLQ; range, 1 [maximum impairment] to 7 [no impairment]), and Asthma Symptom Diary (ASD; range, 0 [no symptoms] to 4 [worst possible symptoms]).

Results

Overall, 1061 patients underwent randomization (529 were assigned to receive tezepelumab and 532 to receive placebo). The annualized rate of asthma exacerbations was 0.93 (95% confidence interval [CI], 0.80 to 1.07) with tezepelumab and 2.10 (95% CI, 1.84 to 2.39) with placebo (rate ratio, 0.44; 95% CI, 0.37 to 0.53; P<0.001). In patients with a blood eosinophil count of less than 300 cells per microliter, the annualized rate was 1.02 (95% CI, 0.84 to 1.23) with tezepelumab and 1.73 (95% CI, 1.46 to 2.05) with placebo (rate ratio, 0.59; 95% CI, 0.46 to 0.75; P<0.001). At week 52, improvements were greater with tezepelumab than with placebo with respect to the prebronchodilator FEV1 (0.23 vs. 0.09 liters; difference, 0.13 liters; 95% CI, 0.08 to 0.18; P<0.001) and scores on the ACQ-6 (1.55 vs. 1.22; difference, 0.33; 95% CI, 0.46 to 0.20; P<0.001), AQLQ (1.49 vs. 1.15; difference, 0.34; 95% CI, 0.20 to 0.47; P<0.001), and ASD (0.71 vs. 0.59; difference, 0.12; 95% CI, 0.19 to 0.04; P=0.002). The frequencies and types of adverse events did not differ meaningfully between the two groups.

Conclusions

Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo.

DOI: 10.1056/NEJMoa2034975

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2034975