Determinants of omalizumab dose-related efficacy in oral immunotherapy: Evidence from a cohort of 181 patients

Background: Omalizumab has been shown to improve the safety and feasibility of oral immunotherapy (OIT), but the optimal dosage strategy is unknown. Objective: Our aim was to identify determinants of omalizumab dose-related efficacy in the context of OIT. Methods: 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. Results: Omalizumab dosage per weight alone was strongly associated with progression through the IFE (chi(2) = 28.18; P<.0001), whereas the standard dosage per weight and total IgE level used for asthma was not (chi(2) = 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 (chi(2) = 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). Conclusion: 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.

Automated summary

In the context of oral immunotherapy (OIT), the dosage of omalizumab should be adjusted based on body weight alone, regardless of total IgE level. The ratio of allergen-specific/total IgE may be useful in predicting patients at higher risk of food dosing reactions after weaning off omalizumab.