Randomized, Placebo-Controlled, Multicenter Trial of Egg Oral Immunotherapy in Children: An Analysis of Clinical Tolerance
Year of Publication
Jones, SM; Burks, AW; Wood, RA; Fleischer, DM; Sicherer, SH; Lindblad, RW; Stablein, D; Henning, AK; Vickery, BP; Liu, AH; Scurlock, AM; Shreffler, WG; Plaut, M; Sampson, HA
AAAAI - American Academy of Allergy, Asthma & Immunology
Journal of Allergy and Clinical Immunology Vol. 129, Issue 2, Supplement, Page AB65
RATIONALE: Oral immunotherapy (OIT) has been used to induce clinical desensitization, but no OIT protocols have been evaluated in well controlled trials to assess tolerance induction. METHODS: Egg-allergic children (5-18 y/o) received daily OIT with egg white (n540) or placebo (n515). Initial escalation, build-up, and maintenance (2000 mg) phases were followed by an oral food challenge (OFC) to egg white at 10, 22, and 24 months. Immune mechanisms were evaluated. RESULTS: Fifty-five subjects enrolled; 6/40 (15%) egg OIT and 2/15 (13.3%) placebo subjects withdrew before 24 months. After 10 months of therapy, 0/15 (0%) placebo and 22/40 (55%) egg OIT subjects were desensitized; after 22 months, 30/40 (75%) were desensitized. Egg OIT was then stopped for 6-8 weeks and subjects underwent another OFC; 11/40 (27.5%) egg OIT subjects passed this OFC and were tolerant. Symptoms during year one of dosing were mild-moderate; 75% of 11,860 egg doses and 96% of 4018 placebo doses were symptom-free. Egg OIT treatment led to the following mechanistic changes: basophil activation declined from baseline to 22 months (p<0.001); prick skin test size declined (p50.02); egg-specific IgG4 increased (p<0.001); egg-specific IgE declined (N.S.). Among egg OIT subjects, smaller PST size at 22 months was correlated with desensitization (p50.009) and tolerance (p50.005), as was change from baseline to 22 months (p50.01). CONCLUSIONS: These results establish that egg OIT can induce desensitization in most patients and clinical tolerance in some. Reductions in basophil and mast cell activation and increases in IgG4 antibody indicate effective immunomodulation and may predict desensitization and tolerance.