Impact of participant baseline factors on exposure-adjusted incidence of treatment-related adverse events during peanut oral immunotherapy.

Abstract

Background: Oral immunotherapy (OIT) causes frequent treatment-related adverse events (AE), particularly during dose-escalation, which can cause treatment withdrawal.

Objective: We aimed to determine whether patient characteristics influenced the frequency of treatment-related AEs during dose escalation.

Methods: Data was obtained from a multicentre, randomised trial (PPOIT-003), involving 201 children aged 1-10 years who received probiotic peanut oral immunotherapy (PPOIT), peanut oral immunotherapy alone (OIT) or placebo. Frequency of AE was expressed as 'exposure-adjusted incidence rate' (EAIR). Multivariable Poisson regression models with interaction terms were used to explore whether baseline participant factors modified the effect of treatment on EAIR of treatment-related AEs during dose escalation.

Results: EAIR of AE in PPOIT and OIT groups were 3-fold higher compared to placebo, with no difference between PPOIT and OIT (PPOIT vs placebo: rate ratio (RR)=3.62 [95% CI 2.92-4.48] p<0.001; OIT vs placebo: RR=3.62 [2.93-4.48] p<0.001; PPOIT vs OIT: RR=1.00 [0.90-1.10] p=0.98). Older children (≥6 years) and females had a higher EAIR in all treatment groups. Allergic sensitivity and pre-existing allergic conditions modified the effect of treatment on EAIR (likelihood ratio test all p<0.001). Children with SPT≥15mm, peanut sIgE≥40kU/L, reaction dose threshold <320mg peanut protein, or history of asthma, allergic rhinitis or anaphylaxis were more likely to report frequent treatment-related AEs when receiving PPOIT or OIT, but not placebo.

Conclusion: Children with higher allergic sensitivity or allergic comorbidities are more likely to experience frequent treatment-related adverse events during peanut OIT dose escalation, and may benefit from more intensive monitoring and support to optimise treatment success.