Department of Pediatrics, Section of Allergy and Clinical Immunology, Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada.
Department of Medicine, Section of Allergy and Clinical Immunology, Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
J Allergy Clin Immunol. 2021 Jan;147(1):233-243. doi: 10.1016/j.jaci.2020.08.039. Epub 2020 Sep 24.
Omalizumab has been shown to improve the safety and feasibility of oral immunotherapy (OIT), but the optimal dosage strategy is unknown.
Our aim was to identify determinants of omalizumab dose-related efficacy in the context of OIT.
The study sample consisted of a clinical cohort of 181 patients treated with omalizumab-enabled oral immunotherapy at 3 centers. Patients received omalizumab for at least 2 months before an initial food escalation (IFE) with a mix of up to 6 allergens. Progression through IFE steps was assessed with survival analysis. Continued food dose tolerance with omalizumab weaning was also documented.
Omalizumab dosage per weight alone was strongly associated with progression through the IFE (χ = 28.18; P < .0001), whereas the standard dosage per weight and total IgE level used for asthma was not (χ = 0.001; P = .97). When the values at time of IFE were estimated through pharmacokinetics and pharmacodynamics simulation, IFE outcome was best predicted by a model that includes levels of free allergen-specific IgE and their interaction with blocking omalizumab-IgE complexes and free omalizumab levels in serum (χ = 65.84; degrees of freedom [df] = 2; P < .0005). The occurrence of immediate-type reactions to food dosing subsequent to weaning of omalizumab was associated with a greater ratio of specific IgE level to total IgE level at baseline (geometric mean 0.39 vs 0.16 in those without symptom; P < .0001).
In the context of OIT and IgE-mediated disease, omalizumab dosages should be adjusted for body weight alone, independently of total IgE level. The fraction of allergen-specific/total IgE may be useful to predict patients at greater risk of food dosing reactions subsequent to weaning.
奥马珠单抗已被证明可提高口服免疫治疗（OIT）的安全性和可行性，但最佳剂量策略尚不清楚。
我们旨在确定奥马珠单抗剂量相关疗效的决定因素，以确定 OIT 的情况。
研究样本由在 3 个中心接受奥马珠单抗辅助口服免疫治疗的 181 例患者的临床队列组成。患者在进行初始食物递增（IFE）之前至少接受 2 个月的奥马珠单抗治疗，IFE 中混合使用了多达 6 种过敏原。通过生存分析评估 IFE 步骤的进展情况。还记录了奥马珠单抗逐渐减少剂量时对食物剂量的持续耐受情况。
奥马珠单抗的剂量与 IFE 的进展（χ 28.18；P <.0001）强烈相关，而用于哮喘的标准剂量与体重和总 IgE 水平无关（χ 0.001；P =.97）。当通过药代动力学和药效动力学模拟估计 IFE 时的数值时，IFE 结果最好通过一个模型来预测，该模型包括游离过敏原特异性 IgE 水平及其与阻断奥马珠单抗-IgE 复合物的相互作用，以及血清中游离奥马珠单抗水平（χ 65.84；自由度[df] 2；P <.0005）。奥马珠单抗逐渐减少剂量后，食物剂量发生速发型反应与基线时特异性 IgE 与总 IgE 水平的比值更高相关（几何平均值分别为 0.39 和 0.16，无症状者；P <.0001）。
在 OIT 和 IgE 介导的疾病背景下，奥马珠单抗的剂量应单独根据体重进行调整，与总 IgE 水平无关。过敏原特异性/总 IgE 的比例可能有助于预测奥马珠单抗逐渐减少剂量后食物剂量反应风险更高的患者。
