Multicenter, randomized, double-blind, placebo-controlled clinical trial of vital wheat gluten oral immunotherapy.

BACKGROUND: Wheat is a common food allergen that can cause anaphylaxis. OBJECTIVE: We sought to determine the efficacy and safety of vital wheat gluten (VWG) oral immunotherapy (OIT). METHODS: After baseline double-blind, placebo-controlled food challenge (DBPCFC), 46 patients with wheat allergy (median age, 8.7 years; range, 4.2-22.3 years) were randomized 1:1 to low-dose VWG OIT or placebo, with biweekly escalation to 1445 mg of wheat protein (WP). After a year 1 DBPCFC, active subjects continued low-dose VWG OIT for another year and underwent a year 2 DBPCFC and, if passed, a subsequent off-therapy DBPCFC. Placebo-treated subjects crossed over to high-dose VWG OIT (maximum, 2748 mg of WP). RESULTS: The median baseline successfully consumed dose (SCD) was 43 mg of WP in both groups. At year 1, 12 (52.2%) of 23 low-dose VWG OIT-treated and 0 (0%) of 23 placebo-treated subjects achieved the primary end point of an SCD of 4443 mg of WP or greater (P < .0001); median SCDs were 4443 and 143 mg, respectively. At year 2, 7 (30.4%) of 23 low-dose VWG OIT-treated subjects were desensitized to an SCD of 7443 mg of WP; 3 (13%) achieved sustained unresponsiveness 8 to 10 weeks off therapy. Among placebo-treated subjects who crossed over to high-dose VWG OIT, 12 (57.1%) of 21 were desensitized after 1 year (median SCD, 7443 mg of WP; nonsignificant vs low-dose VWG OIT). At year 1, skin prick test responses and wheat- and omega-5 gliadin-specific IgE levels did not differ between groups; the low-dose VWG OIT median specific IgG4 level was greater than placebo (wheat, P = .0005; omega-5 gliadin, P = .0001). Year 1 SCDs correlated with wheat-specific (rho = 0.55, P = .0003) and omega-5 gliadin-specific (rho = 0.51, P = .001) IgG4 levels in all subjects. Among 7822 low-dose VWG OIT doses in year 1, 15.4% were associated with adverse reactions: 0.04% were severe, and 0.08% subjects received epinephrine. Among 7921 placebo doses, 5.8% were associated with adverse reactions; none were severe. CONCLUSIONS: Low- and high-dose VWG OIT induced desensitization in about one half of the subjects after 1 year of treatment. Two years of low-dose VWG OIT resulted in 30% desensitization, and 13% had sustained unresponsiveness.