Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China; Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China.
Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China; Graduate School of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Clin Ther. 2021 Jun;43(6):e192-e208. doi: 10.1016/j.clinthera.2021.03.023. Epub 2021 May 4.
Mepolizumab is a human monoclonal antibody against interleukin 5 (IL-5) used to treat severe eosinophilic asthma. Several studies have evaluated the effectiveness of mepolizumab in the real world. We conducted a systematic review and meta-analysis in the context of heterogeneity among patients, clinicians, and treatment regimens to study the effectiveness of mepolizumab in the real world.
We searched the PubMed and Embase databases for real-world studies on severe asthma treatment with mepolizumab as of June 30, 2020. Exacerbations, asthma-related hospitalizations, forced expiratory volume in 1 second (FEV), Asthma Control Questionnaire (ACQ) or Asthma Control Test (ACT), corticosteroid use, peripheral blood eosinophil counts, and the fraction of exhaled nitric oxide were selected as indicators to evaluate the effectiveness. Standardized mean differences by the Cohen method and mean differences were chosen as indicators of effect size. Cohen d values of 0.2, 0.5, and 0.8 are considered as small, medium, and large effects, respectively. We used the Dersimonian-Laird random-effect model to quantify pooled effectiveness estimates.
A total of 1457 patients from 13 studies were included in this review. At all time points, mepolizumab was associated with reductions in exacerbations (2.92 and 2.73 events per patient per year fewer at 6 and 12 months, respectively) and hospitalizations (0.36 events per patient per year fewer at 12 months); improvements in asthma control (ACQ scores reductions of 1.32 and 1.03 at 6 and 12 months, respectively; ACT scores increase of 6.52 at 6-12 months); slight improvements in pulmonary function (FEV increase of 0.23 L at 1-3 months and 6-12 months, respectively); reductions in oral corticosteroid use (9.02- and 7.68-mg decrease at 6 and 12 months, respectively); and reductions in peripheral blood eosinophil counts (decreases of 559.11 cells/μL and 599.17 cells/μL at 1-3 months and 6-12 months, respectively) and fraction of exhaled nitric oxide (13-ppb reduction at 6-12 months).
Our study suggests that mepolizumab is associated with improvements in several clinically meaningful real-world outcomes. This study is a supplement to and extension of the efficacy of randomized controlled trials of mepolizumab.
美泊利珠单抗是一种针对白细胞介素 5（IL-5）的人源单克隆抗体，用于治疗严重的嗜酸性粒细胞性哮喘。有几项研究评估了美泊利珠单抗在真实世界中的疗效。我们在患者、临床医生和治疗方案存在异质性的背景下进行了系统评价和荟萃分析，以研究美泊利珠单抗在真实世界中的疗效。
我们检索了截至 2020 年 6 月 30 日关于美泊利珠单抗治疗严重哮喘的真实世界研究的 PubMed 和 Embase 数据库。我们选择了哮喘加重、哮喘相关住院、用力呼气量（FEV）、哮喘控制问卷（ACQ）或哮喘控制测试（ACT）、皮质类固醇使用、外周血嗜酸性粒细胞计数和呼气一氧化氮分数作为评估疗效的指标。采用 Cohen 法的标准化均数差和均数差作为效应量的指标。Cohen d 值为 0.2、0.5 和 0.8 分别被认为是小、中和大效应。我们使用 Dersimonian-Laird 随机效应模型来量化汇总的有效性估计值。
本综述共纳入了来自 13 项研究的 1457 名患者。在所有时间点，美泊利珠单抗均与减少哮喘加重（6 个月和 12 个月时分别减少 2.92 和 2.73 例/患者/年）和住院（12 个月时减少 0.36 例/患者/年）相关；改善哮喘控制（ACQ 评分分别降低 1.32 和 1.03，6 个月和 12 个月；ACT 评分在 6-12 个月期间增加 6.52）；肺功能略有改善（FEV 在 1-3 个月和 6-12 个月时分别增加 0.23L）；减少口服皮质类固醇的使用（6 个月和 12 个月时分别减少 9.02 和 7.68mg）；以及减少外周血嗜酸性粒细胞计数（1-3 个月和 6-12 个月时分别减少 559.11 个/μL 和 599.17 个/μL）和呼气一氧化氮分数（6-12 个月时减少 13 个 ppb）。
我们的研究表明，美泊利珠单抗与改善几个具有临床意义的真实世界结局有关。本研究是对美泊利珠单抗随机对照试验疗效的补充和扩展。
