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


Journal

The journal of allergy and clinical immunology. In practice
ISSN: 2213-2201
Titre abrégé: J Allergy Clin Immunol Pract
Pays: United States
ID NLM: 101597220

Informations de publication

Date de publication:
05 2021
Historique:
received: 18 09 2020
revised: 24 11 2020
accepted: 10 12 2020
pubmed: 29 12 2020
medline: 25 5 2021
entrez: 28 12 2020
Statut: ppublish

Résumé

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.

Sections du résumé

BACKGROUND
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.
OBJECTIVE
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
Continued daily PTAH treatment beyond 1 year showed sustained safety and efficacy. Ongoing immunomodulation was observed during the second year of treatment.

Identifiants

pubmed: 33359589
pii: S2213-2198(20)31361-1
doi: 10.1016/j.jaip.2020.12.029
pii:
doi:

Substances chimiques

Allergens 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1879-1889.e13

Commentaires et corrections

Type : CommentIn
Type : ErratumIn

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Brian P Vickery (BP)

Emory University School of Medicine, Atlanta, Ga.

Andrea Vereda (A)

Aimmune Therapeutics, London, United Kingdom.

Caroline Nilsson (C)

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

George du Toit (G)

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

Wayne G Shreffler (WG)

Massachusetts General Hospital, Boston, Mass.

A Wesley Burks (AW)

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

Stacie M Jones (SM)

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

Montserrat Fernández-Rivas (M)

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

Katharina Blümchen (K)

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

Jonathan O'B Hourihane (J)

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

Kirsten Beyer (K)

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

Aikaterini Anagnostou (A)

Texas Children's Hospital, Main Hospital, Houston, Texas.

Amal H Assa'ad (AH)

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Moshe Ben-Shoshan (M)

McGill University Health Centre - Montreal Children's Hospital, Montreal, Quebec, Canada.

J Andrew Bird (JA)

Children's Medical Center, Dallas, Texas.

Tara F Carr (TF)

Banner University of Arizona Medical Center, Tucson, Ariz 647.

Warner W Carr (WW)

Allergy & Asthma Associates of Southern California dba Southern California Research, Mission Viejo, Calif.

Thomas B Casale (TB)

University of South Florida, Asthma, Allergy & Immunology Clinical Research Unit, Tampa, Fla.

Hey Jin Chong (HJ)

Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pa.

Christina E Ciaccio (CE)

Comer Children's Hospital, Chicago, Ill.

Morna J Dorsey (MJ)

University of California, San Francisco, San Francisco, Calif.

Stanley M Fineman (SM)

Atlanta Allergy & Asthma Clinic, PA, Marietta, Ga.

Stephen B Fritz (SB)

Idaho Allergy and Research, Eagle, Idaho.

Alexander N Greiner (AN)

Allergy & Asthma Medical Group and Research Center, San Diego, Calif.

Leon S Greos (LS)

Colorado Allergy and Asthma Centers, PC, Denver, Colo.

Frank C Hampel (FC)

Central Texas Health Research, New Braunfels, Texas.

Maria Dolores Ibáñez (MD)

Hospital Clínico San Carlos, Hospital Universitario Niño Jesús, Alergology Department, Madrid, Spain.

David K Jeong (DK)

Virginia Mason Medical Center, Seattle, Wash.

Douglas T Johnston (DT)

Clinical Research of Charlotte, Charlotte, NC.

Rita Kachru (R)

UCLA Medical Center, Santa Monica, Santa Monica, Calif.

Edwin H Kim (EH)

University of North Carolina at Chapel Hill CTRC, Chapel Hill, NC.

Bruce J Lanser (BJ)

National Jewish Health, Denver, Colo.

Stephanie A Leonard (SA)

Rady Children's Hospital San Diego, San Diego, Calif.

Mary C Maier (MC)

Baker Allergy, Asthma and Dermatology Research Center, LLC, Portland, Ore.

Lyndon E Mansfield (LE)

Western Sky Medical Research, El Paso, Texas.

Antonella Muraro (A)

Azienda Ospedaliera di Padova e UOSD Allergie Alimentari, Padova, Italy.

Jason A Ohayon (JA)

Triple A Lab, Hamilton, Ontario, Canada.

Joanna N G Oude Elberink (JNG)

University Medical Center Groningen, Department of Internal Medicine, Division of Allergology, Groningen, Netherlands.

Daniel H Petroni (DH)

Asthma Inc. Clinical Research Center, Seattle, Wash.

Jacqueline A Pongracic (JA)

Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Ill.

Jay M Portnoy (JM)

Children's Mercy on Broadway, Kansas City, Mo.

Rima Rachid (R)

Boston Children's Hospital, Boston, Mass.

Ned T Rupp (NT)

National Allergy and Asthma Research, LLC, N. Charleston, SC.

Georgiana M Sanders (GM)

Michigan Medicine, Michigan Clinical Research Unit, Ann Arbor, Mich.

Hemant P Sharma (HP)

Children's National Medical Center, Washington, DC.

Vibha Sharma (V)

Central Manchester University Hospitals NHS Foundation Trust, Royal Manchester Children's Hospital, Manchester, United Kingdom.

Ellen R Sher (ER)

Atlantic Research Center, LLC, Ocean, NJ.

Lawrence Sher (L)

Peninsula Research Associates, Inc., Rolling Hills Estates, Calif.

Sayantani B Sindher (SB)

Sean N. Parker Center for Allergy and Asthma Research, LPCH at El Camino Hospital, Mountain View, Calif.

Dareen Siri (D)

Sneeze, Wheeze, & Itch Associates, LLC, Normal, Ill.

Jonathan M Spergel (JM)

The Children's Hospital of Philadelphia, Philadelphia, Pa.

Aline B Sprikkelman (AB)

University Medical Center Groningen, Beatrix Children's Hospital, Department of Pediatric Pulmonology & Allergology, Groningen, Netherlands.

Gordon L Sussman (GL)

Gordon Sussman Clinical Research, Inc., Toronto, Ontario, Canada.

Marina Tsoumani (M)

Manchester University NHS Foundation Trust eWythenshawe Hospital, Manchester, United Kingdom.

Pooja Varshney (P)

Specially for Children Allergy, Asthma, and Immunology Clinic, Austin, Texas.

Girish Vitalpur (G)

Indiana University North Hospital, Riley Children's Specialists, Carmel, Ind.

Julie Wang (J)

Icahn School of Medicine at Mount Sinai, Clinical Research Unit, New York, NY.

William H Yang (WH)

Ottawa Allergy Research Corporation, Ottawa, Ontario, Canada.

José Manuel Zubeldia (JM)

Hospital General Universitario Gregorio Marañón, Alergology Department, Madrid, Spain.

Alex Smith (A)

Aimmune Therapeutics, Brisbane, Calif.

Robert Ryan (R)

Aimmune Therapeutics, London, United Kingdom.

Daniel C Adelman (DC)

Aimmune Therapeutics, Brisbane, Calif; Department of Medicine, University of California San Francisco, San Francisco, Calif. Electronic address: dadelman@aimmune.com.

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