Improvements in eliciting dose across baseline sensitivities following 12 months of epicutaneous immunotherapy (EPIT) in peanut-allergic children aged 4 to 11 years

Several potential approaches to food allergy immunotherapy are either approved for restricted use by the US Food and Drug Administration (FDA), offered outside of a regulatory pathway, or are in various stages of clinical development.1-3 Regardless of the approach, these therapies aim to desensitize patients to peanut while supplementing the current standard of care: vigilant avoidance and readiness to manage allergic reactions from unintended ingestion. [...]qualitative research involving caregivers of peanut-allergic children has indicated that any ED/TD increases may be clinically meaningful and meet preference-sensitive care goals of therapy.7,8 Epicutaneous immunotherapy (EPIT) in peanut-allergic children with a 250-μg peanut patch has been shown to be superior to placebo in desensitizing patients to peanut protein in both phase 2 and 3 clinical trials after 12 months of treatment.3,9 In PEPITES, the pivotal phase 3 EPIT efficacy and safety trial, a statistically significant difference (P < .001) between active versus placebo response was observed in children aged 4 to 11 years using responder criteria requiring patients to move either from an ED of ≤10 to ≥300 mg or from >10 to ≥1000 mg.3 The lower bound of the 95% confidence interval (CI) of the difference between placebo and active response rates (difference between treatment arms 21.7%; 95% CI: 12.4-29.8) narrowly missed a prespecified lower bound threshold of 15% agreed on with the FDA, though this margin holds unclear clinical significance for treating peanut-allergic patients.3 As previously reported, a post hoc analysis of the results demonstrated that 62.6% of participants in the active arm versus 28% in the placebo arm experienced an increased ED at month 12 compared with baseline, whereas 6.7% of active versus 33.9% of placebo subjects experienced a decrease,3 equating to a greater than 4-fold odds of improving with treatment (odds ratio [OR] = 4.3; 95% CI: 2.7-7.0) and greater than 7-fold odds of worsening with placebo (OR = 7.1; 95% CI: 3.8-13.4). [...]although both groups entered the phase 3 trial at similar sensitivities (entry geometric mean ED of 70.4 and 78.1 mg, respectively), at exit, the active group increased in geometric mean ED by nearly 4-fold (282.0 mg), whereas the placebo group remained relatively unchanged (79.3 mg) in the intent-to-treat population. Previously published QRA modeling has suggested that, based on their ED changes in PEPITES, patients in the active arm are p