Clinical and Immunological Determinants of Time to Open Oral Food Challenge-Confirmed Tolerance in Children With IgE-Mediated Food Allergy: A Retrospective Cohort Study.

BACKGROUND

The timing of tolerance acquisition in childhood IgE-mediated food allergy is clinically important but has been less well studied than persistence as a binary outcome. We examined clinical and immunological determinants of time to open oral food challenge (OFC)-confirmed tolerance.

METHODS

This retrospective cohort study included 157 children with physician-established IgE-mediated food allergy evaluated at a tertiary pediatric allergy clinic between January 2023 and July 2026. Time zero was defined as elimination-diet initiation; tolerance was defined exclusively by a successful supervised open OFC. One mutually exclusive index allergen was assigned to each child and used consistently to define the time-to-tolerance outcome. Kaplan-Meier analysis and parametric accelerated failure time models were used. The log-logistic model, adjusted for index allergen and the prespecified clinical and immunological covariates, was selected for multivariable analysis and internally validated using 1,000 bootstrap resamples.

RESULTS

Of 157 children, 120 achieved OFC-confirmed tolerance and 37 were right-censored. The mutually exclusive index-allergen distribution was hen's egg (n=103), cow's milk (n=35), tree nut (n=16), other food (n=2), and fish (n=1). In the index-allergen-adjusted log-logistic AFT model, food-induced anaphylaxis (adjusted TR 2.13, 95% CI 1.34-3.36; P=0.001), allergic rhinitis (adjusted TR 1.80, 95% CI 1.26-2.55; P=0.001), and each 10-fold increase in total IgE (adjusted TR 1.54, 95% CI 1.20-1.98; P<0.001) were associated with a longer time to tolerance. Tree-nut index allergy was also associated with longer time to tolerance than hen's egg (adjusted TR 2.74, 95% CI 1.19-6.29; P=0.018), although this estimate was based on few tolerance events.

CONCLUSIONS

Previous food-induced anaphylaxis, allergic rhinitis, higher total IgE, and index food type were associated with the timing of open OFC-confirmed tolerance in children with IgE-mediated food allergy. Routine quantitative IgG, IgA, and IgM measures were not independently associated with tolerance timing.