Abstract：
OBJECTIVE: Monoclonal antibodies (MAbs) have clinical benefits for treating several atopic diseases. However, consensus on its use for eosinophilic esophagitis (EoE) is lacking. The present meta-analysis aimed to compare the efficacy and safety of MAbs versus placebo for treating EoE.
METHODS: We searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs). The primary outcomes were changes in peak esophageal eosinophils count/high power field (HPF) and mean esophageal eosinophils count/HPF. The secondary outcomes were changes in the EoE-Histology Scoring System (EoE-HSS), Endoscopic Reference Score (EREFS), dysphagia score, and adverse events (AEs). We compared binary outcomes using risk ratio (RR) and continuous outcomes using mean difference (MD) or standardized mean difference (SMD), with 95% confidence interval (CI). Considering the diversity of mechanistic properties of MAbs, a pre-specified subgroup analysis by MAb mechanism of action was performed for all outcomes, provided that at least two studies were in each subgroup. Heterogeneity was assessed using Cochran\'s Q test and I2 statistics.
RESULTS: 6 RCTs were included (533 patients). Compared to placebo, MAbs led to a significant reduction in peak esophageal eosinophils count/HPF (MD -0.78; CI 95% -0.87, -0.6801) and mean esophageal eosinophils count/HPF (SMD -0.79; CI 95% -1.5, -0.08). Moreover, MAbs significantly reduced EoE-HSS scores (grade score: SMD -9.31; 95% CI -13.95, -4.6701; stage score: SMD -10.18; 95% CI -15.06, -5.31), EREFS (SMD -5.95; CI 95% -9.19, -2.71) and dysphagia score (SMD -1.79; CI 95% -3.36, -0.23) without increasing AEs compared to placebo. Among those MAbs whose mechanism of action includes the blockage of the receptor for IL-13 (Dupilumab, QAX576, and RPC4046), the scores of EoE-HSS grade, EoE-HSS stage, EREFS, and dysphagia were significantly reduced, and they presented a similar risk of overall and serious AEs compared to placebo.
CONCLUSIONS: MAbs seem effective and safe in reducing esophageal eosinophil infiltrate, EoE-HSS score, EREFS score, and dysphagia symptoms in patients with EoE. However, further evidence is needed to establish its place in EoE management.
METHODS: We searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs). The primary outcomes were changes in peak esophageal eosinophils count/high power field (HPF) and mean esophageal eosinophils count/HPF. The secondary outcomes were changes in the EoE-Histology Scoring System (EoE-HSS), Endoscopic Reference Score (EREFS), dysphagia score, and adverse events (AEs). We compared binary outcomes using risk ratio (RR) and continuous outcomes using mean difference (MD) or standardized mean difference (SMD), with 95% confidence interval (CI). Considering the diversity of mechanistic properties of MAbs, a pre-specified subgroup analysis by MAb mechanism of action was performed for all outcomes, provided that at least two studies were in each subgroup. Heterogeneity was assessed using Cochran\'s Q test and I2 statistics.
RESULTS: 6 RCTs were included (533 patients). Compared to placebo, MAbs led to a significant reduction in peak esophageal eosinophils count/HPF (MD -0.78; CI 95% -0.87, -0.6801) and mean esophageal eosinophils count/HPF (SMD -0.79; CI 95% -1.5, -0.08). Moreover, MAbs significantly reduced EoE-HSS scores (grade score: SMD -9.31; 95% CI -13.95, -4.6701; stage score: SMD -10.18; 95% CI -15.06, -5.31), EREFS (SMD -5.95; CI 95% -9.19, -2.71) and dysphagia score (SMD -1.79; CI 95% -3.36, -0.23) without increasing AEs compared to placebo. Among those MAbs whose mechanism of action includes the blockage of the receptor for IL-13 (Dupilumab, QAX576, and RPC4046), the scores of EoE-HSS grade, EoE-HSS stage, EREFS, and dysphagia were significantly reduced, and they presented a similar risk of overall and serious AEs compared to placebo.
CONCLUSIONS: MAbs seem effective and safe in reducing esophageal eosinophil infiltrate, EoE-HSS score, EREFS score, and dysphagia symptoms in patients with EoE. However, further evidence is needed to establish its place in EoE management.
摘要：
目的：单克隆抗体（MAb）对治疗多种特应性疾病具有临床益处。然而,关于其用于嗜酸性粒细胞性食管炎（EoE）的共识尚不一致。本荟萃分析旨在比较MAb与安慰剂治疗EoE的疗效和安全性。
方法：我们搜索了PubMed，Embase,和Cochrane图书馆进行随机对照试验（RCTs）。主要结果是食管嗜酸性粒细胞峰值计数/高倍视野（HPF）和平均食管嗜酸性粒细胞计数/HPF的变化。次要结果是EoE-组织学评分系统（EoE-HSS）的变化，内窥镜参考评分(EREFS),吞咽困难评分,和不良事件（AE）。我们比较了使用风险比（RR）的二元结果和使用平均差（MD）或标准化平均差（SMD）的连续结果，95%置信区间(CI)。考虑到MAb的机械特性的多样性，通过MAb作用机制对所有结局进行了预先指定的亚组分析，前提是每个亚组至少有两项研究。使用CochranQ检验和I2统计量评估异质性。
结果：纳入6个RCTs（533例）。与安慰剂相比，MAb导致食管嗜酸性粒细胞峰值计数/HPF（MD-0.78;CI95％-0.87，-0.6801）和平均食管嗜酸性粒细胞计数/HPF（SMD-0.79;CI95％-1.5，-0.08）显着降低。此外，MAb显着降低了EoE-HSS得分（等级得分：SMD-9.31；95％CI-13.95，-4.6701；阶段得分：SMD-10.18；95％CI-15.06，-5.31），与安慰剂相比，EREFS（SMD-5.95；CI95％-9.19，-2.71）和吞咽困难评分（SMD-1.79；CI95％-3.36，-0.23）未增加AE。在那些作用机制包括阻断IL-13受体的MAb中（Dupilumab，QAX576和RPC4046),EoE-HSS等级的分数，EoE-HSS阶段,EREFS,吞咽困难明显减少，与安慰剂相比,他们出现总体和严重AE的风险相似.
结论：MAb在减少食管嗜酸性粒细胞浸润方面似乎是有效和安全的，EoE-HSS得分,EREFS得分,EoE患者的吞咽困难症状。然而,需要进一步的证据来确定其在EoE管理中的地位。
方法：我们搜索了PubMed，Embase,和Cochrane图书馆进行随机对照试验（RCTs）。主要结果是食管嗜酸性粒细胞峰值计数/高倍视野（HPF）和平均食管嗜酸性粒细胞计数/HPF的变化。次要结果是EoE-组织学评分系统（EoE-HSS）的变化，内窥镜参考评分(EREFS),吞咽困难评分,和不良事件（AE）。我们比较了使用风险比（RR）的二元结果和使用平均差（MD）或标准化平均差（SMD）的连续结果，95%置信区间(CI)。考虑到MAb的机械特性的多样性，通过MAb作用机制对所有结局进行了预先指定的亚组分析，前提是每个亚组至少有两项研究。使用CochranQ检验和I2统计量评估异质性。
结果：纳入6个RCTs（533例）。与安慰剂相比，MAb导致食管嗜酸性粒细胞峰值计数/HPF（MD-0.78;CI95％-0.87，-0.6801）和平均食管嗜酸性粒细胞计数/HPF（SMD-0.79;CI95％-1.5，-0.08）显着降低。此外，MAb显着降低了EoE-HSS得分（等级得分：SMD-9.31；95％CI-13.95，-4.6701；阶段得分：SMD-10.18；95％CI-15.06，-5.31），与安慰剂相比，EREFS（SMD-5.95；CI95％-9.19，-2.71）和吞咽困难评分（SMD-1.79；CI95％-3.36，-0.23）未增加AE。在那些作用机制包括阻断IL-13受体的MAb中（Dupilumab，QAX576和RPC4046),EoE-HSS等级的分数，EoE-HSS阶段,EREFS,吞咽困难明显减少，与安慰剂相比,他们出现总体和严重AE的风险相似.
结论：MAb在减少食管嗜酸性粒细胞浸润方面似乎是有效和安全的，EoE-HSS得分,EREFS得分,EoE患者的吞咽困难症状。然而,需要进一步的证据来确定其在EoE管理中的地位。
