Phase 2, randomized multi oral immunotherapy with omalizumab 'real life' study.
Phase 2, randomized multi oral immunotherapy with omalizumab 'real life' study.
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第 2 期，使用奥马珠单抗的随机多口服免疫疗法“现实生活”研究。
DOI：
10.1111/all.15217
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发表时间：
2022
期刊：
影响因子：
12.4
通讯作者：
Chinthrajah,RebeccaSharon
中科院分区：
文献类型：
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作者：
Sindher,SayantaniB;Kumar,Divya;Cao,Shu;Purington,Natasha;Long,Andrew;Sampath,Vanitha;Zedeck,StaceyS;Woch,MargaretA;Garcia-Lloret,Maria;Chinthrajah,RebeccaSharon
背景口服免疫疗法（OIT）经常因不良事件（AE）而中断，目前的数据表明，降低OIT剂量可以最大限度地减少AE的严重程度和频率。然而，在多食物OIT（mOIT）中能够脱敏并诱导免疫应答的最小日剂量是未知的。（150 mg，3次给药，每4周一次），随机分配1：1接受mOIT至300或1200 mg总蛋白的总维持剂量，（总剂量包括至少两种，最多五种过敏原），然后在治疗18周后过渡到真实的食物蛋白当量。主要终点是治疗18周后至少2种过敏原的IgG 4/IgE比值较基线升高≥25%的受试者比例。在意向治疗population.ResultsSixty参与者在两个网站的主要疗效和安全性分析。两组中70%的受试者显示至少2种过敏原的sIgG 4/sIgE比值发生变化，治疗组间无差异（OR [95% CI] = 1.00 [0.29，3.49]）。总体而言，300和1200 mg组之间的AE没有差异（19%对17%，p = 0.69），分别conclusionsOur数据表明，血浆标志物的变化是早期诱导的，即使在总蛋白剂量为300 mg，包括多种过敏原时，mOIT与固定剂量奥马珠单抗组合。OIT的长期成功需要确定辅助奥马珠单抗的最佳mOIT剂量。试验RegistrationClinicalTrials.gov（NCT 03181009）。
BackgroundOral immunotherapy (OIT) is frequently discontinued due to adverse events (AEs) and current data suggests that lowering OIT doses can minimize severity and frequency of AEs. However, the minimum daily dose that can enable desensitization and induce immune responses in multi‐food OIT (mOIT) is unknown.MethodsParticipants aged 2–25 years with multi‐food allergies were pretreated with fixed‐dose omalizumab (150 mg, 3 doses, every 4 weeks), and randomized 1:1 to receive mOIT to a total maintenance dose of either 300 or 1200 mg total protein, (total dose includes at least two and up to a max of five allergens) and then transitioned to real‐food protein equivalents after 18 weeks of treatment. The primary endpoint was the proportion of subjects with increases in IgG4/IgE ratio of at least 2 allergens by ≥25% from baseline after 18 weeks of therapy. The primary efficacy and safety analyses were done in the intention‐to‐treat population.ResultsSixty participants were enrolled across two sites. Seventy percent of participants in both arms showed changes in sIgG4/sIgE ratio in at least 2 allergens with no difference between the treatment groups (OR [95% CI] = 1.00 [0.29, 3.49]). Overall, there were no differences in AEs between the 300 and 1200 mg groups (19% vs. 17%,p= .69), respectively.ConclusionsOur data suggest that plasma marker changes are induced early, even at a total protein dose of 300 mg inclusive of multiple allergens when mOIT is combined with fixed‐dose omalizumab. Identification of optimal mOIT dosing with adjunct omalizumab is needed for the long‐term success of OIT.Trial RegistrationClinicalTrials.gov (NCT03181009).