PMID- 34320250 OWN - NLM STAT- MEDLINE DCOM- 20220408 LR - 20220731 IS - 1398-9995 (Electronic) IS - 0105-4538 (Print) IS - 0105-4538 (Linking) VI - 77 IP - 3 DP - 2022 Mar TI - Open-label follow-on study evaluating the efficacy, safety, and quality of life with extended daily oral immunotherapy in children with peanut allergy. PG - 991-1003 LID - 10.1111/all.15027 [doi] AB - 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. CI - (c) 2021 Aimmune Therapeutics. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. FAU - Fernandez-Rivas, Montserrat AU - Fernandez-Rivas M AUID- ORCID: 0000-0003-1748-2328 AD - Allergy Department, Hospital Clinico San Carlos, IdISSC, Madrid, Spain. FAU - Vereda, Andrea AU - Vereda A AD - Aimmune Therapeutics, London, UK. FAU - Vickery, Brian P AU - Vickery BP AD - Emory University School of Medicine, Atlanta, Georgia, USA. FAU - Sharma, Vibha AU - Sharma V AD - Department of Paediatric Allergy and Immunology, Royal Manchester Children's Hospital, Manchester, UK. FAU - Nilsson, Caroline AU - Nilsson C AD - Clinical Science and Education, Sodersjukhuset, Karolinska Institutet, Sachs' Children and Youth Hospital, Stockholm, Sweden. FAU - Muraro, Antonella AU - Muraro A AD - Food Allergy Referral Centre Veneto Region, Department of Woman and Child Health, Padua University Hospital, Padua, Italy. FAU - Hourihane, Jonathan O'B AU - Hourihane JO AD - Paediatrics and Child Health, Royal College of Surgeons in Ireland, Dublin, Ireland. AD - Infant Centre and Pediatrics and Child Health, University College Cork, and HRB Clinical Research Facility-Cork, Cork, Ireland. FAU - DunnGalvin, Audrey AU - DunnGalvin A AUID- ORCID: 0000-0002-1540-3959 AD - Infant Centre and Pediatrics and Child Health, University College Cork, and HRB Clinical Research Facility-Cork, Cork, Ireland. AD - Department of Pediatrics and Pediatric Infectious Diseases, Sechenov University, Moscow, Russia. FAU - du Toit, George AU - du Toit G AUID- ORCID: 0000-0002-0321-2928 AD - Guy's and St. Thomas' NHS Foundation Trust, London, UK. FAU - Blumchen, Katharina AU - Blumchen K AD - Division of Allergology, Pneumology and Cystic Fibrosis, Department of Children and Adolescent Medicine, Goethe University Frankfurt, Frankfurt, Germany. FAU - Beyer, Kirsten AU - Beyer K AD - Division of Pulmonology, Immunology and Critical Care Medicine, Department of Pediatrics, Charite Universtatsmedizin Berlin, Berlin, Germany. FAU - Smith, Alex AU - Smith A AD - Aimmune Therapeutics, Brisbane, California, USA. FAU - Ryan, Robert AU - Ryan R AUID- ORCID: 0000-0003-0827-3153 AD - Aimmune Therapeutics, London, UK. FAU - Adelman, Daniel C AU - Adelman DC AD - Aimmune Therapeutics, Brisbane, California, USA. AD - Department of Medicine, University of California San Francisco, San Francisco, California, USA. FAU - Jones, Stacie M AU - Jones SM AD - University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, Arkansas, USA. LA - eng SI - ClinicalTrials.gov/NCT03201003 SI - ClinicalTrials.gov/NCT02635776 SI - ClinicalTrials.gov/NCT03292484 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210924 PL - Denmark TA - Allergy JT - Allergy JID - 7804028 RN - 0 (Allergens) RN - 0 (Immunologic Factors) SB - IM MH - Administration, Oral MH - Adolescent MH - Allergens MH - Arachis/adverse effects MH - Child MH - Child, Preschool MH - Desensitization, Immunologic/adverse effects/methods MH - *Food Hypersensitivity/etiology MH - Humans MH - Immunologic Factors MH - *Peanut Hypersensitivity/diagnosis/etiology/therapy MH - Quality of Life PMC - PMC9293305 OTO - NOTNLM OT - desensitization OT - food allergy OT - oral immunotherapy OT - peanut allergy OT - quality of life COIS- Montserrat Fernandez-Rivas reports consultancies for Aimmune Therapeutics, DBV, Novartis, SPRIM; research funding from European Commission, MINECO and ISCIII of Spanish government; speakers bureau for ALK, Allergy Therapeutics, Diater, Fundacion SEAIC, GSK, HAL Allergy, Thermo Fisher Scientific. Andrea Vereda is an employee and stockholder of Aimmune Therapeutics. Brian P Vickery reports advisory board/consultant: Aimmune Therapeutics, AllerGenis, FARE, Reacta; site investigator: Aimmune Therapeutics, DBV, Genentech, Regeneron; research grants: FARE, NIAID. Vibha Sharma reports speaker fees from Aimmune Therapeutics outside the submitted work. Caroline Nilsson reports grants to institution and advisory board fees from Aimmune Therapeutics and Novartis and speakers fees from MEDA, ALK, Thermo Fisher, GSK. Antonella Muraro reports personal fees from DVB Technologies, Aimmune, Nestle-Purina, Nestle Health Institute, Mylan, and Nutricia outside the submitted work. Jonathan O'B. Hourihane reports advisory board fees, Aimmune Therapeutics; speakers bureau, Aimmune Therapeutics, DBV Technologies, Nutricia, Mead Johnson; grants to institution/research funding, and clinical trials within past 2 years, Aimmune Therapeutics, DBV Technologies. Audrey DunnGalvin reports personal fees from Aimmune Therapeutics and DBV Technologies outside the submitted work. George du Toit reports research grants to institution and advisory board fees from Aimmune Therapeutics. Katharina Blumchen reports consulting for Aimmune Therapeutics, DBV Technologies, Bencard Allergie, HAL Allergy; speakers bureau for Aimmune Therapeutics, DBV Technologies, HAL Allergy, Nutricia, Thermo Fisher Scientific, ALK, Allergopharma, Nestle; and conducting clinical trials for Aimmune Therapeutics, DBV Technologies, and Hipp. Kirsten Beyer reports advisory board/consulting fees from Aimmune Therapeutics, ALK, Bausch & Lomb, Bencard, Danone, DBV, Hycor, Infectopharm, Mabylon, Meda Pharma, Mylan, Nestle; speakers bureau for Aimmune Therapeutics, Allergopharma, Bencard, Danone, Di-Text, Hammer und Rall Media, Infectopharm, Meda Pharma, Med Update, Nestle, Nutricia; and research grants from Aimmune, ALK, Danone, DBV, Good Mills, Hipp, Hycor, Infectopharm, Nutricia, ThermoFisher, VDI. Alex Smith is an employee and stockholder of Aimmune Therapeutics. Robert Ryan an employee and stockholder of Aimmune Therapeutics. Daniel C. Adelman was an employee and stockholder of Aimmune Therapeutics at the time of the development of this work. He has patents pending for the following: US 16/542,198; PCT/US2019/046706; US 16/721,805; PCT/US2019/067634. Stacie M. Jones reports advisory board fees, Aimmune Therapeutics, FARE; personal fees, DBV Technologies; clinical trials grants, Aimmune Therapeutics, DBV Technologies, Astellas, Sanofi, Regeneron, FARE, Genentech, and NIH-NIAID. EDAT- 2021/07/29 06:00 MHDA- 2022/04/09 06:00 PMCR- 2022/07/18 CRDT- 2021/07/28 17:29 PHST- 2020/12/08 00:00 [received] PHST- 2021/07/09 00:00 [accepted] PHST- 2021/07/29 06:00 [pubmed] PHST- 2022/04/09 06:00 [medline] PHST- 2021/07/28 17:29 [entrez] PHST- 2022/07/18 00:00 [pmc-release] AID - ALL15027 [pii] AID - 10.1111/all.15027 [doi] PST - ppublish SO - Allergy. 2022 Mar;77(3):991-1003. doi: 10.1111/all.15027. Epub 2021 Sep 24.