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Antigen-specific IgG2 and IgG3 are rarely measured in food allergy clinical trials despite known function in preventing mast cell and basophil activation. Our objective was to determine whether measuring peanut-specific IgG2 and IgG3 levels would correlate with peanut allergy status. Peanut-specific IgG subclasses were measured via ELISA assays in Learning Early About Peanut allergy (LEAP) trial participants at 5 years of age and were correlated with peanut allergy vs peanut sensitization vs non-peanut allergic and peanut consumption vs peanut avoidance. Peanut-specific IgG1, IgG2, IgG3, and IgG4 levels were significantly different between participants with peanut allergy vs peanut sensitization vs non-peanut allergic, and a multivariate logistic regression model and stepwise selection found that IgG1 most closely associated with peanut allergy status. Similarly, all subclasses differentiated those consuming vs those avoiding peanut, but subsequent modeling found that IgG4 most closely associated with consumption status. Amongst the peanut-specific IgG subclasses, IgG1 was the best biomarker for peanut allergy, while IgG4 was the best biomarker for peanut antigen exposure in this highly atopic cohort. Our study did not find added value from evaluating peanut-specific IgG 2 and 3 as biomarkers of peanut allergy, although they did correlate with peanut allergy. Subsequent studies should assess the value of adding IgG subclasses to multivariate models predicting peanut allergy status.

Background: Oral immunotherapy containing peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) (Palforzia [Aimmune Therapeutics, Brisbane, Calif]) for 9 to 12 months resulted in higher tolerated amounts of peanut protein in PTAH-treated individuals aged 4 to 17 years with peanut allergy than in placebo-treated participants. Objective: We aimed to describe additional long-term pooled safety data and changes in peanut sensitization markers from baseline through approximately 5 years of treatment. Methods: The results from 6 clinical trials of PTAH (3 controlled and 3 open-label extension studies [N = 1227]) were pooled, and analysis of safety outcomes and immunologic data was performed. The PTAH doses were administered sequentially as follows: initial dose escalation (dose increased to 6 mg over 2 days), updosing (dose increased every 2 weeks to 300 mg for a minimum of 6 months), and maintenance dosing (300 mg per day). Results: There was a trend toward decreased adverse events (AEs) at years 1 and 2 that was maintained up to 5 years, with 94% of patients experiencing mild or moderate AEs and only 13% discontinuing PTAH use because of AEs overall. Gastrointestinal symptoms were the most commonly reported treatment-related AEs. A downward trend in systemic allergic reactions was also reported. PTAH treatment resulted in reduced levels of peanut-specific IgE after the first year and increased levels of peanut-specific IgG4, with a lowered peanut-specific IgE:IgG4 ratio. A reduction in median peanut skin prick test wheal diameter was observed (11.50 mm at baseline vs 5.75 mm at year 5). Conclusion: Long-term immunomodulation without any new safety signals was reported with PTAH immunotherapy in the largest safety data set and longest treatment duration for oral immunotherapy published to date.