Epicutaneous immunotherapy for the treatment of peanut allergy in children and young adults

Abstract

Background: Peanut allergy is common, life-threatening, and without therapeutic options. We evaluated peanut epicutaneous immunotherapy (EPIT) by using Viaskin Peanut for peanut allergy treatment.

Objective: We sought to evaluate the clinical, safety, and immunologic effects of EPIT for the treatment of peanut allergy.

Methods: In this multicenter, double-blind, randomized, placebo-controlled study, 74 participants with peanut allergy (ages 4-25 years) were treated with placebo (n = 25), Viaskin Peanut 100 μg (VP100; n = 24) or Viaskin Peanut 250 μg (VP250; n = 25; DBV Technologies, Montrouge, France). The primary outcome was treatment success after 52 weeks, which was defined as passing a 5044-mg protein oral food challenge or achieving a 10-fold or greater increase in successfully consumed dose from baseline to week 52. Adverse reactions and mechanistic changes were assessed.

Results: At week 52, treatment success was achieved in 3 (12%) placebo-treated participants, 11 (46%) VP100 participants, and 12 (48%) VP250 participants (P = .005 and P = .003, respectively, compared with placebo; VP100 vs VP250, P = .48). Median change in successfully consumed doses were 0, 43, and 130 mg of protein in the placebo, VP100, and VP250 groups, respectively (placebo vs VP100, P = .014; placebo vs VP250, P = .003). Treatment success was higher among younger children (P = .03; age, 4-11 vs >11 years). Overall, 14.4% of placebo doses and 79.8% of VP100 and VP250 doses resulted in reactions, predominantly local patch-site and mild reactions (P = .003). Increases in peanut-specific IgG4 levels and IgG4/IgE ratios were observed in peanut EPIT-treated participants, along with trends toward reduced basophil activation and peanut-specific TH2 cytokines.

Conclusions: Peanut EPIT administration was safe and associated with a modest treatment response after 52 weeks, with the highest responses among younger children. This, when coupled with a high adherence and retention rate and significant changes in immune pathways, supports further investigation of this novel therapy.

Keywords: IgE; Peanut hypersensitivity; desensitization; epicutaneous; food allergy; immunotherapy.

Conflict of interest statement

Disclosure of potential conflict of interest: S. M. Jones receives grant support form FARE, Aimmune Technologies, DBV Technologies, the National Peanut Board, and the National Institutes of Health (NIH)/National Institutes of Allergy and Infectious Diseases (NIAID); serves as a consultant for Stallergenes; and receives payment for lectures from the Kansas City Allergy Society, Mercy Children’s Hospital, Riley Children’s Hospital, Southwestern Medical School–Children’s Medical Center, the European Academy of Allergy and Clinical Immunology, the New York Allergy & Asthma Society, the University of Iowa-Seebohm Lectureship in Allergy, and the Iowa Society of Allergy, Asthma & Immunology. S. H. Sicherer receives grant support from the NIAID and FARE and royalties from UpToDate and serves as an Associate Editor of the Journal of Allergy and Clinical Immunology: In Practice. A. W. Burks receives grant funding from the NIH, Wallace Foundation and Food Allergy & Anaphylaxis; serves on the board for FARE, the NIH AITC Review Panel, the NIH HAI Study Section, Stallergenes, the World Allergy Organization, and the American Academy of Allergy, Asthma & Immunology; serves as a consultant for ActoGeniX, Adept Field Solutions, Dow AgroSciences, ExploraMed Development, Genentech, GLG Research, Insys Therapeutics, Merck, Regeneron Pharmaceuticals, Sanofi-Aventis US, SRA International, Valeant Pharmaceuticals North America, and Epiva Biosciences; manuscript preparation from the American Society for Microbiology; and holds stock in Allertein and Mastcell Pharmaceuticals. D. Y. M. Leung receives grant funding from the NIH. R. W. Lindblad receives grant funding from the NIH. P. Dawson receives grant funding from the NIH. A. K. Henning receives grant funding from the NIH. D. Chiang receives grant funding from the NIH. B. P. Vickery receives grant support from the NIAID, is an employee of Aimmune Therapeutics, and holds stock options in Aimmune Therapeutics. R. D. Pesek receives grant funding from the NIH, Kedrion, AstraZeneca, Parrigo Nutritionals, and Danone Research. H. A. Sampson receives grant support from the NIAID and DBV Technologies; serves as a consultant for Allertein therapeutics, Genentech/Roche, Sanofi, Stallergenes, Sanone, and Merck; is a part time employee of DBV Technologies; receives royalties from UpToDate and Elsevier; and received stock from DBV Technologies. R. A. Wood receives grant support from the NIAID, DBVAimmune, Astellas, and HAL-Allergy; serves as a consultant for Stallergenes and Sanofi; and received royalties from UpToDate. The rest of the authors declare that they have no relevant conflicts of interest.

Copyright © 2016 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Figures

FIG 1.

CONSORT diagram. Enrollment and randomization of younger participants aged 4 to less than 6 years was conducted as in the full study population, as indicated. Enrollment was paused after the first 10 participants were enrolled for a predetermined interim DSMB safety review after 35 days (21 days of escalation and 14 days of maintenance) of dosing to ensure tolerability of the study product. Because of completed study enrollment, no further participants in the 4- to less than 6-year-old age range were enrolled after the DSMB review.

FIG 2.

SCD from baseline to the week 52 OFC. A, Analysis by treatment group. B, Analysis by age and treatment group. Top panels represent the 4- to 11-year-old age group. Bottom panels represent the greater than 11-year-old age group. Solid lines represent median values, and hatched lines represent the upper and lower IQR.

FIG 3.

Immune mechanistic assessments over time by treatment group. A, Change in peanut-specific IgE levels over time. No significant differences over time were seen between treatment groups (P = .37). B, Change in peanut-specific IgG4 levels over time. A significant difference over time was seen between treatment groups (P < .0001), with a larger increase noted among the active Viaskin Peanut groups compared with the placebo group. C, Change in the peanut IgG4/IgE ratio over time. A significant difference over time was seen between treatment groups (P < .0001), with a larger increase noted among the active Viaskin Peanut groups compared with the placebo group. Solid lines represent median values, and hatched lines represent the upper and lower IQR.

FIG 4.

SPT results over time by treatment group. No significant difference was noted among treatment groups over time; however, when examined within a treatment group, a decrease in SPT size was noted in the VP250 group (P = .02). Solid lines represent median values, and hatched lines represent the upper and lower IQR.