Safety of peanut (Arachis hypogaea) allergen powder-dnfp in children and teenagers with peanut allergy: Pooled summary of phase 3 and extension trials.


Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
06 2022
Historique:
received: 22 02 2021
revised: 09 12 2021
accepted: 20 12 2021
pubmed: 1 1 2022
medline: 9 6 2022
entrez: 31 12 2021
Statut: ppublish

Résumé

Peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; previously known as AR101) is a daily oral immunotherapy approved to mitigate allergic reactions after accidental peanut exposure in peanut-allergic individuals aged 4-17 years. We sought to comprehensively summarize the PTAH safety profile for up to ∼2 years of treatment. Safety and adverse event (AE) data from participants aged 4-17 years from 3 controlled, phase 3 and 2 open-label extension trials were pooled and assessed. Of the 944 individuals receiving ≥1 PTAH dose, median exposure was ∼49 weeks; most participants experienced ≥1 treatment-related AE (TRAE; n = 853; 90.4%). A total of 829 participants experienced TRAEs with a maximum severity of mild (497, 52.6%) or moderate (332, 35.2%); 24 participants (2.5%) experienced TRAEs graded as severe. Overall, 80 participants (9.5%) discontinued as a result of AEs; most experienced gastrointestinal symptoms and discontinued during the first 6 months. When adjusted for exposure, AEs and TRAEs occurred at a rate of 76.4 and 58.7 events per participant-year of exposure (PYE), respectively, during updosing; AEs and TRAEs decreased to 23.0 and 14.2, respectively, during 300 mg maintenance. Overall, exposure-adjusted rates of systemic allergic reactions were 0.12 events/PYE (mild), 0.11 events/PYE (moderate), and 0.01 events/PYE (severe [anaphylaxis]). The safety profile of PTAH was consistent across trials, manageable, and improved over time. AEs were predominantly mild to moderate, and all grades declined in frequency with continued treatment. These data can be used to facilitate shared decision-making discussions with patients and families considering treatment with PTAH.

Sections du résumé

BACKGROUND
Peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; previously known as AR101) is a daily oral immunotherapy approved to mitigate allergic reactions after accidental peanut exposure in peanut-allergic individuals aged 4-17 years.
OBJECTIVE
We sought to comprehensively summarize the PTAH safety profile for up to ∼2 years of treatment.
METHODS
Safety and adverse event (AE) data from participants aged 4-17 years from 3 controlled, phase 3 and 2 open-label extension trials were pooled and assessed.
RESULTS
Of the 944 individuals receiving ≥1 PTAH dose, median exposure was ∼49 weeks; most participants experienced ≥1 treatment-related AE (TRAE; n = 853; 90.4%). A total of 829 participants experienced TRAEs with a maximum severity of mild (497, 52.6%) or moderate (332, 35.2%); 24 participants (2.5%) experienced TRAEs graded as severe. Overall, 80 participants (9.5%) discontinued as a result of AEs; most experienced gastrointestinal symptoms and discontinued during the first 6 months. When adjusted for exposure, AEs and TRAEs occurred at a rate of 76.4 and 58.7 events per participant-year of exposure (PYE), respectively, during updosing; AEs and TRAEs decreased to 23.0 and 14.2, respectively, during 300 mg maintenance. Overall, exposure-adjusted rates of systemic allergic reactions were 0.12 events/PYE (mild), 0.11 events/PYE (moderate), and 0.01 events/PYE (severe [anaphylaxis]).
CONCLUSION
The safety profile of PTAH was consistent across trials, manageable, and improved over time. AEs were predominantly mild to moderate, and all grades declined in frequency with continued treatment. These data can be used to facilitate shared decision-making discussions with patients and families considering treatment with PTAH.

Identifiants

pubmed: 34971646
pii: S0091-6749(21)02740-8
doi: 10.1016/j.jaci.2021.12.780
pii:
doi:

Substances chimiques

Allergens 0
Emollients 0
Powders 0

Types de publication

Clinical Trial, Phase III Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2043-2052.e9

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Kari R Brown (KR)

Aimmune Therapeutics, a Nestlé Health Science company, Brisbane, Calif. Electronic address: kbrown@aimmune.com.

James Baker (J)

Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, Mich.

Andrea Vereda (A)

Aimmune Therapeutics, a Nestlé Health Science company, London, United Kingdom.

Kirsten Beyer (K)

Charité Universitãtsmedizin Berlin, Berlin, Germany.

A Wesley Burks (AW)

Department of Pediatrics, University of North Carolina Food Allergy Initiative, Division of Allergy, Immunology and Rheumatology, University of North Carolina at Chapel Hill, Chapel Hill, NC.

George du Toit (G)

Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.

Jonathan O'B Hourihane (J)

Paediatrics and Child Health, Royal College of Surgeons in Ireland, Dublin, Ireland.

Stacie M Jones (SM)

University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, Ark.

David Norval (D)

Aimmune Therapeutics, a Nestlé Health Science company, London, United Kingdom.

Adrian Dana (A)

Aimmune Therapeutics, a Nestlé Health Science company, Brisbane, Calif.

Wayne Shreffler (W)

Massachusetts General Hospital, Boston, Mass.

Brian P Vickery (BP)

Emory University School of Medicine, Atlanta, Ga.

Thomas Casale (T)

University of South Florida, Tampa, Fla.

Ben Skeel (B)

Aimmune Therapeutics, a Nestlé Health Science company, London, United Kingdom.

Daniel Adelman (D)

Aimmune Therapeutics, a Nestlé Health Science company, Brisbane, Calif; Department of Medicine, University of California San Francisco, San Francisco, Calif.

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Classifications MeSH