Open-label follow-on study evaluating the efficacy, safety, and quality of life with extended daily oral immunotherapy in children with peanut allergy.


Journal

Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028

Informations de publication

Date de publication:
03 2022
Historique:
received: 08 12 2020
accepted: 09 07 2021
pubmed: 29 7 2021
medline: 9 4 2022
entrez: 28 7 2021
Statut: ppublish

Résumé

The benefit of daily administration of Peanut (Arachis hypogaea) Allergen Powder-dnfp (PTAH)-formerly AR101-has been established in clinical trials, but limited data past the first year of treatment are available. This longitudinal analysis aimed to explore the impact of continued PTAH therapeutic maintenance dosing (300 mg/day) on efficacy, safety/tolerability, and food allergy-related quality of life. We present a subset analysis of PALISADE-ARC004 participants (aged 4-17 years) who received 300 mg PTAH daily for a total of ~1.5 (Group A, n = 110) or ~2 years (Group B, n = 32). Safety assessments included monitoring the incidence of adverse events (AEs), accidental exposures to food allergens, and adrenaline use. Efficacy was assessed by double-blind, placebo-controlled food challenge (DBPCFC); skin prick testing; peanut-specific antibody assays; and Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM) scores. Continued maintenance with PTAH increased participants' ability to tolerate peanut protein: 48.1% of completers in Group A (n = 50/104) and 80.8% in Group B (n = 21/26) tolerated 2000 mg peanut protein at exit DBPCFC without dose-limiting symptoms. Immune biomarkers showed a pattern consistent with treatment-induced desensitization. Among PTAH-continuing participants, the overall and treatment-related exposure-adjusted AE rate decreased throughout the intervention period in both groups. Clinically meaningful improvements in FAQLQ and FAIM scores over time suggest a potential link between increased desensitization as determined by the DBPCFC and improved quality of life. These results demonstrate that daily PTAH treatment for peanut allergy beyond 1 year leads to an improved safety/tolerability profile and continued clinical and immunological response.

Sections du résumé

BACKGROUND
The benefit of daily administration of Peanut (Arachis hypogaea) Allergen Powder-dnfp (PTAH)-formerly AR101-has been established in clinical trials, but limited data past the first year of treatment are available. This longitudinal analysis aimed to explore the impact of continued PTAH therapeutic maintenance dosing (300 mg/day) on efficacy, safety/tolerability, and food allergy-related quality of life.
METHODS
We present a subset analysis of PALISADE-ARC004 participants (aged 4-17 years) who received 300 mg PTAH daily for a total of ~1.5 (Group A, n = 110) or ~2 years (Group B, n = 32). Safety assessments included monitoring the incidence of adverse events (AEs), accidental exposures to food allergens, and adrenaline use. Efficacy was assessed by double-blind, placebo-controlled food challenge (DBPCFC); skin prick testing; peanut-specific antibody assays; and Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM) scores.
RESULTS
Continued maintenance with PTAH increased participants' ability to tolerate peanut protein: 48.1% of completers in Group A (n = 50/104) and 80.8% in Group B (n = 21/26) tolerated 2000 mg peanut protein at exit DBPCFC without dose-limiting symptoms. Immune biomarkers showed a pattern consistent with treatment-induced desensitization. Among PTAH-continuing participants, the overall and treatment-related exposure-adjusted AE rate decreased throughout the intervention period in both groups. Clinically meaningful improvements in FAQLQ and FAIM scores over time suggest a potential link between increased desensitization as determined by the DBPCFC and improved quality of life.
CONCLUSIONS
These results demonstrate that daily PTAH treatment for peanut allergy beyond 1 year leads to an improved safety/tolerability profile and continued clinical and immunological response.

Identifiants

pubmed: 34320250
doi: 10.1111/all.15027
pmc: PMC9293305
doi:

Substances chimiques

Allergens 0
Immunologic Factors 0

Banques de données

ClinicalTrials.gov
['NCT03201003', 'NCT02635776', 'NCT03292484']

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

991-1003

Informations de copyright

© 2021 Aimmune Therapeutics. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

Références

Expert Rev Mol Diagn. 2004 May;4(3):273-9
pubmed: 15137895
Immunol Allergy Clin North Am. 2015 Feb;35(1):45-59
pubmed: 25459576
J Allergy Clin Immunol. 2016 Apr;137(4):1128-1137.e1
pubmed: 26806049
J Allergy Clin Immunol Pract. 2019 Feb;7(2):479-491.e10
pubmed: 30423449
J Allergy Clin Immunol. 2011 Mar;127(3):603-7
pubmed: 21093026
Allergy. 2007 Aug;62(8):857-71
pubmed: 17590200
Clin Pediatr (Phila). 2011 Nov;50(11):1045-51
pubmed: 21685213
Allergy. 2010 May;65(5):630-5
pubmed: 19845570
Allergy. 2020 Nov;75(11):2920-2935
pubmed: 32438514
Allergy. 2017 Aug;72(8):1133-1147
pubmed: 28058751
J Allergy Clin Immunol. 2008 Jul;122(1):139-44, 144.e1-2
pubmed: 18602570
N Engl J Med. 2012 Jul 19;367(3):233-43
pubmed: 22808958
Allergy. 2009 Aug;64(8):1209-17
pubmed: 19210345
JAMA Netw Open. 2019 Jan 4;2(1):e185630
pubmed: 30646188
Clin Exp Allergy. 2009 Jan;39(1):127-37
pubmed: 19016799
J Allergy Clin Immunol Pract. 2019 Sep - Oct;7(7):2241-2249
pubmed: 31051271
Allergy. 2014 Aug;69(8):992-1007
pubmed: 24816523
Lancet. 2019 Oct 19;394(10207):1437-1449
pubmed: 31522849
J Allergy Clin Immunol. 2014 Nov;134(5):1016-25.e43
pubmed: 25174862
Pediatrics. 2018 Dec;142(6):
pubmed: 30455345
Clin Exp Allergy. 2010 Mar;40(3):476-85
pubmed: 20210816
Sci Transl Med. 2017 Aug 2;9(401):
pubmed: 28768806
N Engl J Med. 2018 Nov 22;379(21):1991-2001
pubmed: 30449234
World Allergy Organ J. 2020 Sep 18;13(8):100455
pubmed: 33005286
Allergy. 2022 Mar;77(3):991-1003
pubmed: 34320250
Lancet Child Adolesc Health. 2020 Oct;4(10):728-739
pubmed: 32702315
J Allergy Clin Immunol Pract. 2021 May;9(5):1879-1889.e14
pubmed: 33359589
J Allergy Clin Immunol Pract. 2017 Mar - Apr;5(2):363-368.e2
pubmed: 28017626

Auteurs

Montserrat Fernandez-Rivas (M)

Allergy Department, Hospital Clinico San Carlos, IdISSC, Madrid, Spain.

Andrea Vereda (A)

Aimmune Therapeutics, London, UK.

Brian P Vickery (BP)

Emory University School of Medicine, Atlanta, Georgia, USA.

Vibha Sharma (V)

Department of Paediatric Allergy and Immunology, Royal Manchester Children's Hospital, Manchester, UK.

Caroline Nilsson (C)

Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Sachs' Children and Youth Hospital, Stockholm, Sweden.

Antonella Muraro (A)

Food Allergy Referral Centre Veneto Region, Department of Woman and Child Health, Padua University Hospital, Padua, Italy.

Jonathan O'B Hourihane (JO)

Paediatrics and Child Health, Royal College of Surgeons in Ireland, Dublin, Ireland.
Infant Centre and Pediatrics and Child Health, University College Cork, and HRB Clinical Research Facility-Cork, Cork, Ireland.

Audrey DunnGalvin (A)

Infant Centre and Pediatrics and Child Health, University College Cork, and HRB Clinical Research Facility-Cork, Cork, Ireland.
Department of Pediatrics and Pediatric Infectious Diseases, Sechenov University, Moscow, Russia.

George du Toit (G)

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

Katharina Blumchen (K)

Division of Allergology, Pneumology and Cystic Fibrosis, Department of Children and Adolescent Medicine, Goethe University Frankfurt, Frankfurt, Germany.

Kirsten Beyer (K)

Division of Pulmonology, Immunology and Critical Care Medicine, Department of Pediatrics, Charité Universtãtsmedizin Berlin, Berlin, Germany.

Alex Smith (A)

Aimmune Therapeutics, Brisbane, California, USA.

Robert Ryan (R)

Aimmune Therapeutics, London, UK.

Daniel C Adelman (DC)

Aimmune Therapeutics, Brisbane, California, USA.
Department of Medicine, University of California San Francisco, San Francisco, California, USA.

Stacie M Jones (SM)

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

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH