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

J Allergy Clin Immunol. 2019 Feb;143(2):651-661.e9. doi: 10.1016/j.jaci.2018.08.041. Epub 2018 Oct 30.


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.

Keywords: Wheat allergy; desensitization; food allergy; gluten; oral immunotherapy; oral tolerance; sustained unresponsiveness.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Allergens / immunology
  • Allergens / therapeutic use*
  • Anaphylaxis / immunology
  • Anaphylaxis / prevention & control*
  • Child
  • Child, Preschool
  • Desensitization, Immunologic / methods*
  • Double-Blind Method
  • Female
  • Glutens / immunology
  • Humans
  • Immune Tolerance
  • Male
  • Placebos
  • Treatment Outcome
  • Triticum / immunology
  • Wheat Hypersensitivity / immunology
  • Wheat Hypersensitivity / therapy*
  • Young Adult


  • Allergens
  • Placebos
  • Glutens