Effect of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Ingestion Among Children With Peanut Allergy

Abstract

IMPORTANCE There are currently no approved treatments for peanut allergy. OBJECTIVE To assess the efficacy and adverse events of epicutaneous immunotherapy with a peanut patch among peanut-allergic children. DESIGN, SETTING, AND PARTICIPANTS Phase 3, randomized, double-blind, placebo-controlled trial conducted at 31 sites in 5 countries between January 8, 2016, and August 18, 2017. Participants included peanut-allergic children (aged 4-11 years [n = 356] without a history of a severe anaphylactic reaction) developing objective symptoms during a double-blind, placebo-controlled food challenge at an eliciting dose of 300 mg or less of peanut protein. INTERVENTIONS Daily treatment with peanut patch containing either 250 μg of peanut protein (n = 238) or placebo (n = 118) for 12 months. MAIN OUTCOMES AND MEASURES The primary outcome was the percentage difference in responders between the peanut patch and placebo patch based on eliciting dose (highest dose at which objective signs/symptoms of an immediate hypersensitivity reaction developed) determined by food challenges at baseline and month 12. Participants with baseline eliciting dose of10mgorlesswererespondersiftheposttreatmentelicitingdosewas300mgormore;participants with baseline eliciting dose greater than 10 to 300 mg were responders if the posttreatment eliciting dose was 1000 mg or more. A threshold of 15% or more on the lower bound of a 95% CI around responder rate difference was prespecified to determine a positive trial result. Adverse event evaluation included collection of treatment-emergent adverse events (TEAEs). RESULTS Among 356 participants randomized (median age, 7 years; 61.2% male), 89.9% completed the trial; the mean treatment adherence was 98.5%. The responder rate was 35.3% with peanut-patch treatment vs 13.6% with placebo (difference, 21.7% [95% CI, 12.4%-29.8%; P < .001]). The prespecified lower bound of the CI threshold was not met. TEAEs, primarily patch application site reactions, occurred in 95.4% and 89% of active and placebo groups, respectively. The all-causes rate of discontinuation was 10.5% in the peanut-patch group vs 9.3% in the placebo group. CONCLUSIONS AND RELEVANCE Among peanut-allergic children aged 4 to 11 years, the percentage difference in responders at 12 months with the 250-μg peanut-patch therapy vs placebo was 21.7% and was statistically significant, but did not meet the prespecified lower bound of the confidence interval criterion for a positive trial result. The clinical relevance of not meeting this lower bound of the confidence interval with respect to the treatment of peanut-allergic children with epicutaneous immunotherapy remains to be determined.

Development of a novel Ara h 2 hypoallergen with no IgE binding or anaphylactogenic activity

“…17 Hence other routes of application (oral, sublingual, and epicutaneous) were developed, but these approaches require further studies to prove their safety and long-term efficacy. [18][19][20] Several designs of hypoallergenic Ara h 2 derivatives were tested in vitro and in animals to produce safe vaccine components. 7,12,33 These studies aimed to elucidate the contribution of either linear or conformational epitopes of Ara h 2 to IgE binding and effector cell activation.…”

“…18 Sublingual and epicutaneous immunotherapies represent promising approaches, but further studies regarding long-term effectiveness and safety are required. 19,20 Ara h 2, the most important peanut allergen, is an essential component of any vaccine for patients with peanut allergy. Therefore hypoallergenic Ara h 2 mutants with removed B-cell but retained T-cell epitopes are candidates for future immunotherapeutics.…”

Recent developments and highlights in food allergy

“…It showed 21.6% more responders using EPIT than placebo, which was significant with very good safety data; however, the trial missed the predetermined lower confidence boundary of a 15% difference and was therefore considered negative. 152,153 Given the adverse reactions experienced with OIT, adjunctive treatments are being investigated as has recently been reviewed. [154][155][156][157] Adjunctive therapies being investigated include TLR4 agonists, TLR9 agonists, nanoparticles encapsulating peanut allergen, Chinese herbal medicine (food allergy herbal formula [FAHF-2]), probiotics, biologicals including omalizumab, anti-histamines, and leukotriene receptor antagonists.…”

Long-term sublingual immunotherapy for peanut allergy in children: Clinical and immunologic evidence of desensitization

“…6,7 Both oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT) strategies have advanced to late-stage clinical trials and review by the US Food and Drug Administration for use in treating peanut allergy. 8,9 However, OIT might have potential limitations in terms of safety and ease of administration, and EPIT might be limited in its ability to generate clinically meaningful immunologic changes. Sublingual immunotherapy (SLIT) could represent a viable alternative for patients because of its simple route of administration and the good overall safety and efficacy seen in smaller trials.…”