PDF(Pubmed)
Abstract：
We aimed to determine whether mepolizumab, an anti-IL-5 antibody, was more effective than placebo for improving dysphagia symptoms and decreasing oesophageal eosinophil counts in eosinophilic oesophagitis (EoE).
We conducted a multicentre, randomised, double-blind, placebo-controlled, trial. In the first part, patients aged 16-75 with EoE and dysphagia symptoms (per EoE Symptom Activity Index (EEsAI)) were randomised 1:1 to 3 months of mepolizumab 300 mg monthly or placebo. Primary outcome was change in EEsAI from baseline to month 3 (M3). Secondary outcomes included histological, endoscopic and safety metrics. In part 2, patients initially randomised to mepolizumab continued 300 mg monthly for 3 additional months (mepo/mepo), placebo patients started mepolizumab 100 mg monthly (pbo/mepo), and outcomes were reassessed at month 6 (M6).
Of 66 patients randomised, 64 completed M3, and 56 completed M6. At M3, EEsAI decreased 15.4±18.1 with mepolizumab and 8.3±18.0 with placebo (p=0.14). Peak eosinophil counts decreased more with mepolizumab (113±77 to 36±43) than placebo (146±94 to 160±133) (p<0.001). With mepolizumab, 42% and 34% achieved histological responses of <15 and ≤6 eos/hpf compared with 3% and 3% with placebo (p<0.001 and 0.02). The change in EoE Endoscopic Reference Score at M3 was also larger with mepolizumab. At M6, EEsAI decreased 18.3±18.1 points for mepo/mepo and 18.6±19.2 for pbo/mepo (p=0.85). The most common adverse events were injection-site reactions.
Mepolizumab did not achieve the primary endpoint of improving dysphagia symptoms compared with placebo. While eosinophil counts and endoscopic severity improved with mepolizumab at 3 months, longer treatment did not yield additional improvement.
NCT03656380.
We conducted a multicentre, randomised, double-blind, placebo-controlled, trial. In the first part, patients aged 16-75 with EoE and dysphagia symptoms (per EoE Symptom Activity Index (EEsAI)) were randomised 1:1 to 3 months of mepolizumab 300 mg monthly or placebo. Primary outcome was change in EEsAI from baseline to month 3 (M3). Secondary outcomes included histological, endoscopic and safety metrics. In part 2, patients initially randomised to mepolizumab continued 300 mg monthly for 3 additional months (mepo/mepo), placebo patients started mepolizumab 100 mg monthly (pbo/mepo), and outcomes were reassessed at month 6 (M6).
Of 66 patients randomised, 64 completed M3, and 56 completed M6. At M3, EEsAI decreased 15.4±18.1 with mepolizumab and 8.3±18.0 with placebo (p=0.14). Peak eosinophil counts decreased more with mepolizumab (113±77 to 36±43) than placebo (146±94 to 160±133) (p<0.001). With mepolizumab, 42% and 34% achieved histological responses of <15 and ≤6 eos/hpf compared with 3% and 3% with placebo (p<0.001 and 0.02). The change in EoE Endoscopic Reference Score at M3 was also larger with mepolizumab. At M6, EEsAI decreased 18.3±18.1 points for mepo/mepo and 18.6±19.2 for pbo/mepo (p=0.85). The most common adverse events were injection-site reactions.
Mepolizumab did not achieve the primary endpoint of improving dysphagia symptoms compared with placebo. While eosinophil counts and endoscopic severity improved with mepolizumab at 3 months, longer treatment did not yield additional improvement.
NCT03656380.
摘要：
目的：我们的目的是确定美泊利单抗，抗IL-5抗体,在改善吞咽困难症状和减少嗜酸性粒细胞性食管炎（EoE）的食道嗜酸性粒细胞计数方面比安慰剂更有效。
方法：我们进行了多中心，随机化，双盲,安慰剂对照,审判。在第一部分,有EoE和吞咽困难症状(根据EoE症状活动指数(EEsAI))的16~75岁患者被随机分为1:1~3个月,每月服用美泊利单抗300mg或安慰剂.主要结果是EEsAI从基线到第3个月（M3）的变化。次要结果包括组织学，内窥镜和安全指标。在第2部分中，最初随机接受美泊利单抗治疗的患者每月持续300mg，再持续3个月（mepo/mepo），安慰剂患者每月服用100毫克美泊利单抗（pbo/mepo），结果在第6个月(M6)重新评估.
结果：在随机分组的66名患者中，64完成M3，56完成M6。在M3时，MEpolizumab的EEsAI降低了15.4±18.1，安慰剂的EEsAI降低了8.3±18.0（p=0.14）。与安慰剂组(146±94至160±133)相比,美泊利单抗组(113±77至36±43)的嗜酸性粒细胞峰值减少更多(p<0.001)。有了美波利单抗，42%和34%达到<15和≤6eos/hpf的组织学反应，而安慰剂为3%和3%(p<0.001和0.02)。使用美泊利单抗时，M3时EoE内窥镜参考评分的变化也更大。在M6时，EEsAI对于mepo/mepo降低了18.3±18.1点，对于pbo/mepo降低了18.6±19.2点（p=0.85）。最常见的不良事件是注射部位反应。
结论：与安慰剂相比，美泊利单抗未达到改善吞咽困难症状的主要终点。尽管3个月时使用美泊利单抗可改善嗜酸性粒细胞计数和内镜下严重程度，更长的处理没有产生额外的改善。
背景：NCT03656380。
方法：我们进行了多中心，随机化，双盲,安慰剂对照,审判。在第一部分,有EoE和吞咽困难症状(根据EoE症状活动指数(EEsAI))的16~75岁患者被随机分为1:1~3个月,每月服用美泊利单抗300mg或安慰剂.主要结果是EEsAI从基线到第3个月（M3）的变化。次要结果包括组织学，内窥镜和安全指标。在第2部分中，最初随机接受美泊利单抗治疗的患者每月持续300mg，再持续3个月（mepo/mepo），安慰剂患者每月服用100毫克美泊利单抗（pbo/mepo），结果在第6个月(M6)重新评估.
结果：在随机分组的66名患者中，64完成M3，56完成M6。在M3时，MEpolizumab的EEsAI降低了15.4±18.1，安慰剂的EEsAI降低了8.3±18.0（p=0.14）。与安慰剂组(146±94至160±133)相比,美泊利单抗组(113±77至36±43)的嗜酸性粒细胞峰值减少更多(p<0.001)。有了美波利单抗，42%和34%达到<15和≤6eos/hpf的组织学反应，而安慰剂为3%和3%(p<0.001和0.02)。使用美泊利单抗时，M3时EoE内窥镜参考评分的变化也更大。在M6时，EEsAI对于mepo/mepo降低了18.3±18.1点，对于pbo/mepo降低了18.6±19.2点（p=0.85）。最常见的不良事件是注射部位反应。
结论：与安慰剂相比，美泊利单抗未达到改善吞咽困难症状的主要终点。尽管3个月时使用美泊利单抗可改善嗜酸性粒细胞计数和内镜下严重程度，更长的处理没有产生额外的改善。
背景：NCT03656380。
