Pauline Azzano1, Maxime Paquin2, Alexandra Langlois1, Charles Morin3, Guy Parizeault3, Jonathan Lacombe-Barrios1, Kathryn Samaan1, François Graham2, Louis Paradis4, Anne Des Roches1, Philippe Bégin5. 1. Department of Pediatrics, Section of Allergy and Clinical Immunology, Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada. 2. Department of Medicine, Section of Allergy and Clinical Immunology, Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada. 3. Department of Pediatrics, Hôpital de Chicoutimi, Saguenay, Québec, Canada. 4. 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. 5. 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; Department of Pediatrics, Hôpital de Chicoutimi, Saguenay, Québec, Canada. Electronic address: philippe.begin@umontreal.ca.
Abstract
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 (χ2 = 28.18; P < .0001), whereas the standard dosage per weight and total IgE level used for asthma was not (χ2 = 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 (χ2 = 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.
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 (χ2 = 28.18; P < .0001), whereas the standard dosage per weight and total IgE level used for asthma was not (χ2 = 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 (χ2 = 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.