Peanut allergy (PA) affects approximately 1% to 1.5% of children and adults living in westernized society¹ and is considered a life-long allergy in the vast majority of subjects.^{2, 3} Additionally, peanuts and tree nuts account for 90% of all cases of fatal and near-fatal anaphylaxis to foods.⁴ Strict dietary avoidance and availability of injectable epinephrine are key management tools in the current food allergy guidelines,² and the quest for effective allergen immunotherapy for PA is ongoing.⁵

Epicutaneous immunotherapy (EPIT) has shown promise in animal studies^{6, 7, 8} and in a single pilot study⁹ as a novel future treatment for food allergy. Preclinical studies indicate that allergen applied through EPIT to intact skin does not cross into the circulation but rather activates dendritic cells in the dermal layer of the skin to affect immune activation.⁵ The findings presented in this letter expand the data presented in abstract form¹⁰ to include a comprehensive analysis of the phase 1 study. The purpose of this study was to evaluate the safety and tolerability of peanut EPIT when the new Viaskin Peanut patch (DBV Technologies, Bagneux, France) is applied on intact skin of subjects with PA.

One hundred subjects (n = 80 receiving active treatment; n = 20 receiving placebo treatment) aged 6 to 50 years, including 70 subjects with nonsevere PA (adults: n = 40, age range, 18-50 years; adolescents: n = 20; age range, 12-17 years; and children: n = 10; age range, 6-11 years) and 30 adults with severe PA, were enrolled in a randomized, double-blind, placebo-controlled phase 1b study at 5 clinical sites in the United States (see Table E1 for study sites, Table E2 for inclusion/exclusion criteria, and Table E3 for nonsevere/severe definitions in this article’s Online Repository at www.jacionline.org). Subjects were randomized 4:1 (peanut/placebo) to receive Viaskin Peanut treatment in dosing cohorts at doses of 20, 100, 250, and 500 μg or placebo applied to intact skin of the upper arm or interscapular space of the back at either 24- or 48-hour intervals during a 2-week dosing period with a 1-week follow-up. Subjects were enrolled sequentially, starting with the low-dose Viaskin Peanut patch in the nonsevere adult cohort and then progressing on to the next dose escalation in the nonsevere adult cohorts by using an interactive Web-based response system. Data and Safety Monitoring Board (DSMB) review occurred before progression of dosing at all stages. The nonsevere adult cohorts were completed before progressing to the adolescent and then child dosing cohorts. The adult cohorts with severe PA were enrolled after DSMB review of the nonsevere adult cohorts. The child cohort did not receive the 500-μg dose after DSMB review (see Fig E1 in this article’s Online Repository at www.jacionline.org).

Study visits were scheduled on days 1, 2, 3, 8, and 15 of dosing and on day 22 (7 days after completion of dosing) to assess the safety and tolerability of the study product. Subjects recorded Viaskin application/removal and any patch site symptoms (pruritus, erythema, edema, and urticaria) and severity by using daily diary assessments. Viaskin patch site and atopic dermatitis (AD) scores were assessed by the investigative team at study visits.

The safety and tolerability of peanut EPIT were assessed by means of evaluation for the presence and severity of treatment-emergent adverse events (TEAEs; reactions not at the Viaskin site only) and local treatment-emergent adverse events (L-TEAEs; local Viaskin site only), the severity of those events, any treatment required, and adherence to therapy. Adverse events were coded according to the Medical Dictionary for Regulatory Activities, version 13.0. Data were pooled and summarized by cohort dosing group and analyzed by using χ² or Fisher exact tests to compare the proportion of events between treatment groups.

Table E4 in this article’s Online Repository at www.jacionline.org shows the clinical characteristics of the study population. The majority of subjects were male, non-Hispanic white subjects with a median age of 22 years (range, 6-49 years) and with other atopic diseases, including asthma (63%), allergic rhinitis (45%), and AD/eczema (37%). The mean baseline peanut IgE level was 25.47 kilounits of antibody per liter (kU_A/L; range, 0.71->100 kU_A/L).

Overall, TEAEs were mostly mild and transient, with no differences between treatment groups (Fig 1 and seeFig E2 and Tables E5 and E6 in this article’s Online Repository at www.jacionline.org). For subjects who received Viaskin Peanut, 42 (52.5%) of 80 reported at least 1 TEAE, 41.3% of mild severity and 11.3% of moderate severity. For subjects who received placebo, 9 (45%) of 20 reported at least 1 TEAE, 30% of mild severity and 15% of moderate severity. No severe TEAEs were reported, and 47.5% of Viaskin Peanut–treated subjects and 55% of placebo-treated subjects reported no TEAEs. No reports of severe adverse events or epinephrine use occurred. There were no statistically significant differences in the proportion of subjects reporting TEAEs when comparing the placebo and Viaskin Peanut treatment groups and between subjects with nonsevere and those with severe PA.