Methods: After baseline-DBPCFC, 46 wheat-allergic-subjects, median age 8.7 years (range: 4.2-22.3), 78% male, were randomized 1:1 to active-WOIT with high-gluten- wheat-flour or placebo. They escalated bi-weekly to maximum 1445mg wheat protein (WP) followed by year-1-DBPCFC. Active-WOIT-subjects continued an additional year, underwent year-2-DBPCFC, and if passed, off-therapy-DBPCFC. Placebo-subjects crossed-over to 1-year high-dose-active-WOIT, maximum 3870mg WP.
Results: At baseline-DBPCFC, median successfully consumed dose (SCD) was 43mg WP in both groups. At year-1, 12/23(52.2%) WOIT and 0/23(0%) placebo-subjects achieved the primary endpoint (SCD≥4443mg WP, p<0.0001; median SCD 4443mg vs. 143mg, p<0.0001). At year-2, 7/23(30.4%) WOIT-subjects were desensitized (SCD 7443mg WP); 3/23(13.0%) achieved sustained unresponsiveness (SU) 8-10 weeks off-WOIT (SCD 7443mg WP). At crossover-year-1, 14/21(66.7%) High-Dose-Crossover-subjects had SCD > 4443mg WP (non-significant vs. active-WOIT); 12/21(57.1%) were desensitized, median SCD 7443mg. Year-1-skin prick test, wheat- and omega-5-gliadin-sIgE didn’t differ between groups. In WOIT, median-year-1-sIgG4 was greater than placebo: wheat (22.0 vs. 3.05 mgA/L, p=0.0005), omega-5-gliadin (7.34 vs. 0.62 mgA/L, p=0.0001). High-Dose-Crossover-subjects had crossover-year-1 median-wheat-sIgG4 >30mgA/L; omega-5-gliadin-sIgG4, 14.5mgA/L, non-significant vs. WOIT. Year-1-SCD correlated with year-1-wheat (rho=0.56, p=0.0002) and omega-5-gliadin-sIgG4 (0.49, p= 0.002). Among 21,044 WOIT/crossover-doses, 11.2% had adverse reactions; 0.02% severe, 0.05% received epinephrine; non-significant WOIT vs. High-Dose-Crossover. Among 7,922 placebo-doses, 6.0% had adverse reactions; none severe/received epinephrine. Dropouts included: placebo-2, crossover-3, active-WOIT-5.
Conclusions: Lower and high dose-WOIT significantly increased SCD and sIgG4 at year-1 compared to placebo; they weren’t statistically different regarding SCD or dosing symptoms. Two years of lower dose-WOIT achieved 30% desensitization and 13% SU.