Continuous and Daily Oral Immunotherapy for Peanut Allergy: Results from a 2-Year Open-Label Follow-On Study

• Published in: The journal of allergy and clinical immunology in practice (Cambridge, MA) Vol. 9; no. 5; p. 1879
• Main Authors: Vickery, Brian P, Vereda, Andrea, Nilsson, Caroline, du Toit, George, Shreffler, Wayne G, Burks, A Wesley, Jones, Stacie M, Fernández-Rivas, Montserrat, Blümchen, Katharina, O'B Hourihane, Jonathan, Beyer, Kirsten, Smith, Alex, Ryan, Robert, Adelman, Daniel C
• Format: Journal Article
• Language: English
• Published: United States 01.05.2021
• Subjects: Administration, Oral; Adolescent; Allergens; Arachis; Child; Desensitization, Immunologic; Double-Blind Method; Humans; Peanut Hypersensitivity - therapy; Desensitization; Allergic reactions; Dosing regimens; Peanut allergy; Oral immunotherapy
• ISSN: 2213-2201
• DOI: 10.1016/j.jaip.2020.12.029

The randomized, controlled PALISADE trial demonstrated the benefit of daily oral immunotherapy with Peanut (Arachis Hypogaea) allergen powder-dnfp (PTAH, formerly AR101) in peanut-allergic children and adolescents. ARC004, the open-label follow-on study to PALISADE, used 5 dosing cohorts to explore PTAH treatment beyond 1 year and alternative dosing regimens in peanut-allergic individuals. Active arm (PTAH-continuing) PALISADE participants who tolerated 300-mg peanut protein at the exit double-blind placebo-controlled food challenge and placebo arm (PTAH-naive) participants could enter ARC004. PTAH-continuing participants were assigned to receive daily (cohorts 1 and 3A) or non-daily (cohorts 2, 3B, and 3C) dosing regimens; PTAH-naive participants were built up to 300 mg/d PTAH, followed by maintenance dosing. At study completion, participants underwent an exit double-blind placebo-controlled food challenge with doses up to 2000 mg peanut protein. Data were assessed using descriptive statistics. Overall, 358 (87.5%) eligible participants (4-17 years) entered ARC004 (PTAH-continuing, n = 256; PTAH-naive, n = 102). Among PTAH-continuing participants, exposure-adjusted adverse event rates were 12.94 to 17.54/participant-year and 25.95 to 42.49/participant-year in daily and non-daily dosing cohorts, respectively; most participants (83%) experienced mild or moderate adverse events. Daily dosing cohorts appeared to have higher desensitization rates than non-daily dosing cohorts. Of all PTAH-continuing cohorts, cohort 3A had the longest daily dosing duration and the highest desensitization rates. Changes in immune markers with PTAH continuation demonstrated ongoing immunomodulation. Outcomes in PTAH-naive participants mirrored those of the PALISADE active arm. Continued daily PTAH treatment beyond 1 year showed sustained safety and efficacy. Ongoing immunomodulation was observed during the second year of treatment.