Randomized Trial of Milk Oral Immunotherapy: Fixed Low-Dose vs Escalation to Medium-Dose.

Abstract

The optimal oral immunotherapy (OIT) protocol following low-dose desensitization remains unclear. To compare the efficacy and safety of fixed low-dose versus escalation to medium dose for severe cow's milk allergy. This study included children who had a positive oral food challenge (OFC) to 3 mL of milk before initiating OIT, had continued low-dose OIT targeting 3 mL for a minimum of 1 year, and subsequently failed OFC with 25 mL. They were randomized (32 children each) into "fixed-dose group; 3-mL target (99-mg protein)" or "dose-escalation group; 25-mL target (825-mg protein)." Short-term unresponsiveness to 25 mL was assessed using the OFC at 1 and 2 years after the 2-week avoidance. The fixed-dose group versus the dose-escalation group had the following characteristics, respectively: median age (9.2 vs 9.1 years), history of anaphylaxis (94% vs 100%), milk-specific IgE level (19.9 vs 27.0 kU_A/L), and period from OIT initiation (2.0 vs 1.8 years). The rates of achieving 25 mL short-term unresponsiveness were 31% and 28% at 1 year and 47% and 44% at 2 years, respectively (P > .99). The total symptom frequency per OIT dose was 0.9% versus 3.8% in the first year, and 0.8% versus 2.0% in the second year (P < .001), and anaphylaxis was 0.01% versus 0.06% in the first year. Milk-, casein-, α-lactalbumin-, and β-lactoglobulin-specific IgE levels decreased from baseline at 2 years in both groups (P < .001). The fixed low-dose OIT protocol following low-dose desensitization provides comparable efficacy and improved safety compared with dose escalation.