Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford, California, USA.
Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, California, USA.
Allergy. 2022 Jun;77(6):1873-1884. doi: 10.1111/all.15217. Epub 2022 Jan 24.
Oral 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.
Participants 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.
Sixty 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.
Our 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.
ClinicalTrials.gov (NCT03181009).
由于不良反应（AEs），口服免疫疗法（OIT）经常被中断，目前的数据表明降低 OIT 剂量可以最小化 AEs 的严重程度和频率。然而，在多食物 OIT（mOIT）中能够实现脱敏并诱导免疫反应的最小日剂量尚不清楚。
年龄在 2-25 岁之间的多食物过敏参与者接受固定剂量奥马珠单抗（150mg，3 剂，每 4 周）预处理，并以 1:1 的比例随机分配至接受 mOIT 治疗，总维持剂量为 300 或 1200mg 总蛋白（总剂量至少包括两种最多五种过敏原），然后在治疗 18 周后过渡到实际食物蛋白当量。主要终点是在治疗 18 周后，至少有 2 种过敏原的 IgG4/IgE 比值增加至少 25%的受试者比例。主要疗效和安全性分析是在意向治疗人群中进行的。
两个地点共招募了 60 名参与者。两个治疗组中均有 70%的参与者在至少 2 种过敏原中 IgG4/sIgE 比值发生变化，治疗组之间无差异（OR[95%CI]=1.00[0.29,3.49]）。总体而言，300mg 和 1200mg 组之间的不良反应发生率无差异（19%与 17%，p=0.69）。
我们的数据表明，即使在结合固定剂量奥马珠单抗时，mOIT 的总蛋白剂量为 300mg 且包含多种过敏原，也能早期诱导血浆标志物发生变化。需要确定与奥马珠单抗联合使用的最佳 mOIT 剂量，以实现 OIT 的长期成功。
ClinicalTrials.gov（NCT03181009）。
