Division of Allergy and Clinical Immunology Brigham and Women's Hospital and Harvard Medical School, Boston, Mass; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Md.
Georgetown College of Medicine, Washington, DC.
J Allergy Clin Immunol. 2022 Nov;150(5):1097-1105.e12. doi: 10.1016/j.jaci.2022.05.024. Epub 2022 Jun 27.
The comparative safety and efficacy of the biologics currently approved for asthma are unclear.
We compared the safety and efficacy of mepolizumab, benralizumab, and dupilumab in individuals with severe eosinophilic asthma.
We performed a systematic review of peer-reviewed literature published 2000 to 2021. We studied Bayesian network meta-analyses of exacerbation rates, prebronchodilator FEV, the Asthma Control Questionnaire, and serious adverse events in individuals with eosinophilic asthma.
Eight randomized clinical trials (n = 6461) were identified. We found in individuals with eosinophils ≥300 cells/μL the following: in reducing exacerbation rates compared to placebo: dupilumab (risk ratio [RR], 0.32; 95% credible interval [CI], 0.23 to 0.45), mepolizumab (RR, 0.37; 95% CI, 0.30 to 0.45), and benralizumab (RR, 0.49; 95% CI, 0.43 to 0.55); in improving FEV: dupilumab (mean difference in milliliters [MD] 230; 95% CI, 160 to 300), benralizumab (MD, 150; 95% CI, 100 to 200), and mepolizumab (MD, 150; 95% CI, 66 to 220); and in reducing Asthma Control Questionnaire scores: mepolizumab (MD, -0.63; 95% CI, -0.81 to -0.45), dupilumab (MD, -0.48; 95% CI, -0.83 to -0.14), and benralizumab (MD, -0.32; 95% CI, -0.43 to -0.21). In individuals with eosinophils 150-299 cells/μL, benralizumab (RR, 0.62; 95% CI, 0.52 to 0.73) and dupilumab (RR, 0.60; 95% CI, 0.38 to 0.95) were associated with lower exacerbation rates; and only benralizumab (MD, 81; 95% CI, 8 to 150) significantly improved FEV. These differences were minimal compared to clinically important thresholds. For serious adverse events in the overall population, mepolizumab (odds ratio, 0.67; 95% CI, 0.48 to 0.92) and benralizumab (odds ratio, 0.74; 95% CI, 0.59 to 0.93) were associated with lower odds of a serious adverse event, while dupilumab was not different from placebo (odds ratio, 1.0; 95% CI, 0.74 to 1.4).
There are minimal differences in the efficacy and safety of mepolizumab, benralizumab, and dupilumab in eosinophilic asthma.
目前批准用于哮喘的生物制剂的安全性和疗效尚不清楚。
我们比较了美泊利珠单抗、贝那利珠单抗和度匹鲁单抗在重度嗜酸性粒细胞性哮喘患者中的安全性和疗效。
我们对 2000 年至 2021 年发表的同行评议文献进行了系统评价。我们研究了嗜酸性粒细胞性哮喘患者的加重率、支气管扩张剂前 FEV1、哮喘控制问卷和严重不良事件的贝叶斯网络荟萃分析。
确定了 8 项随机临床试验（n=6461）。我们发现，与安慰剂相比，在嗜酸性粒细胞≥300 个/μL的患者中：减少加重率：度匹鲁单抗（风险比[RR]，0.32；95%可信区间[CI]，0.23 至 0.45）、美泊利珠单抗（RR，0.37；95%CI，0.30 至 0.45）和贝那利珠单抗（RR，0.49；95%CI，0.43 至 0.55）；改善 FEV1：度匹鲁单抗（毫升[MD]差值，230；95%CI，160 至 300）、贝那利珠单抗（MD，150；95%CI，100 至 200）和美泊利珠单抗（MD，150；95%CI，66 至 220）；降低哮喘控制问卷评分：美泊利珠单抗（MD，-0.63；95%CI，-0.81 至-0.45）、度匹鲁单抗（MD，-0.48；95%CI，-0.83 至-0.14）和贝那利珠单抗（MD，-0.32；95%CI，-0.43 至-0.21）。在嗜酸性粒细胞为 150-299 个/μL 的患者中，贝那利珠单抗（RR，0.62；95%CI，0.52 至 0.73）和度匹鲁单抗（RR，0.60；95%CI，0.38 至 0.95）与较低的加重率相关；仅贝那利珠单抗（MD，81；95%CI，8 至 150）显著改善了 FEV1。与临床重要阈值相比，这些差异微不足道。对于总体人群中的严重不良事件，美泊利珠单抗（比值比，0.67；95%CI，0.48 至 0.92）和贝那利珠单抗（比值比，0.74；95%CI，0.59 至 0.93）与严重不良事件的发生几率较低相关，而度匹鲁单抗与安慰剂无差异（比值比，1.0；95%CI，0.74 至 1.4）。
在嗜酸性粒细胞性哮喘中，美泊利珠单抗、贝那利珠单抗和度匹鲁单抗在疗效和安全性方面差异极小。
