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Efficacy and safety of oral immunotherapy in children aged 1-3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study.

التفاصيل البيبلوغرافية
العنوان: Efficacy and safety of oral immunotherapy in children aged 1-3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study.
المؤلفون: Jones SM; Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, AR, USA. Electronic address: jonesstaciem@uams.edu., Kim EH; Departments of Medicine and Pediatrics, University of North Carolina, Chapel Hill, NC, USA., Nadeau KC; Department of Pediatrics and Sean N Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, CA, USA., Nowak-Wegrzyn A; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pediatrics, New York University Langone Health, New York, NY, USA., Wood RA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Sampson HA; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Scurlock AM; Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, AR, USA., Chinthrajah S; Department of Pediatrics and Sean N Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, CA, USA., Wang J; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Pesek RD; Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, AR, USA., Sindher SB; Department of Pediatrics and Sean N Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, CA, USA., Kulis M; Departments of Medicine and Pediatrics, University of North Carolina, Chapel Hill, NC, USA., Johnson J; Rho Federal Systems Division, Durham, NC, USA., Spain K; Rho Federal Systems Division, Durham, NC, USA., Babineau DC; Rho Federal Systems Division, Durham, NC, USA., Chin H; Rho Federal Systems Division, Durham, NC, USA., Laurienzo-Panza J; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Yan R; The Immune Tolerance Network, San Francisco, CA, USA., Larson D; The Immune Tolerance Network, Bethesda, MD, USA., Qin T; The Immune Tolerance Network, Bethesda, MD, USA., Whitehouse D; The Immune Tolerance Network, San Francisco, CA, USA., Sever ML; Rho Federal Systems Division, Durham, NC, USA., Sanda S; The Immune Tolerance Network, San Francisco, CA, USA., Plaut M; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Wheatley LM; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Burks AW; Departments of Medicine and Pediatrics, University of North Carolina, Chapel Hill, NC, USA.
مؤلفون مشاركون: Immune Tolerance Network
المصدر: Lancet (London, England) [Lancet] 2022 Jan 22; Vol. 399 (10322), pp. 359-371.
نوع المنشور: Journal Article; Multicenter Study; Randomized Controlled Trial
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: England NLM ID: 2985213R Publication Model: Print Cited Medium: Internet ISSN: 1474-547X (Electronic) Linking ISSN: 01406736 NLM ISO Abbreviation: Lancet Subsets: MEDLINE
أسماء مطبوعة: Publication: 2004- : London : Elsevier
Original Publication: London : J. Onwhyn
مواضيع طبية MeSH: Desensitization, Immunologic*, Allergens/*administration & dosage , Arachis/*immunology , Peanut Hypersensitivity/*prevention & control, Administration, Oral ; Allergens/immunology ; Child ; Child, Preschool ; Double-Blind Method ; Female ; Humans ; Immune Tolerance ; Male ; Peanut Hypersensitivity/immunology ; Treatment Outcome
مستخلص: Background: For young children with peanut allergy, dietary avoidance is the current standard of care. We aimed to assess whether peanut oral immunotherapy can induce desensitisation (an increased allergic reaction threshold while on therapy) or remission (a state of non-responsiveness after discontinuation of immunotherapy) in this population.
Methods: We did a randomised, double-blind, placebo-controlled study in five US academic medical centres. Eligible participants were children aged 12 to younger than 48 months who were reactive to 500 mg or less of peanut protein during a double-blind, placebo-controlled food challenge (DBPCFC). Participants were randomly assigned by use of a computer, in a 2:1 allocation ratio, to receive peanut oral immunotherapy or placebo for 134 weeks (2000 mg peanut protein per day) followed by 26 weeks of avoidance, with participants and study staff and investigators masked to group treatment assignment. The primary outcome was desensitisation at the end of treatment (week 134), and remission after avoidance (week 160), as the key secondary outcome, were assessed by DBPCFC to 5000 mg in the intention-to-treat population. Safety and immunological parameters were assessed in the same population. This trial is registered on ClinicalTrials.gov, NCT03345160.
Findings: Between Aug 13, 2013, and Oct 1, 2015, 146 children, with a median age of 39·3 months (IQR 30·8-44·7), were randomly assigned to receive peanut oral immunotherapy (96 participants) or placebo (50 participants). At week 134, 68 (71%, 95% CI 61-80) of 96 participants who received peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 who received placebo met the primary outcome of desensitisation (risk difference [RD] 69%, 95% CI 59-79; p<0·0001). The median cumulative tolerated dose during the week 134 DBPCFC was 5005 mg (IQR 3755-5005) for peanut oral immunotherapy versus 5 mg (0-105) for placebo (p<0·0001). After avoidance, 20 (21%, 95% CI 13-30) of 96 participants receiving peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 receiving placebo met remission criteria (RD 19%, 95% CI 10-28; p=0·0021). The median cumulative tolerated dose during the week 160 DBPCFC was 755 mg (IQR 0-2755) for peanut oral immunotherapy and 0 mg (0-55) for placebo (p<0·0001). A significant proportion of participants receiving peanut oral immunotherapy who passed the 5000 mg DBPCFC at week 134 could no longer tolerate 5000 mg at week 160 (p<0·001). The participant receiving placebo who was desensitised at week 134 also achieved remission at week 160. Compared with placebo, peanut oral immunotherapy decreased peanut-specific and Ara h2-specific IgE, skin prick test, and basophil activation, and increased peanut-specific and Ara h2-specific IgG4 at weeks 134 and 160. By use of multivariable regression analysis of participants receiving peanut oral immunotherapy, younger age and lower baseline peanut-specific IgE was predictive of remission. Most participants (98% with peanut oral immunotherapy vs 80% with placebo) had at least one oral immunotherapy dosing reaction, predominantly mild to moderate and occurring more frequently in participants receiving peanut oral immunotherapy. 35 oral immunotherapy dosing events with moderate symptoms were treated with epinephrine in 21 participants receiving peanut oral immunotherapy.
Interpretation: In children with a peanut allergy, initiation of peanut oral immunotherapy before age 4 years was associated with an increase in both desensitisation and remission. Development of remission correlated with immunological biomarkers. The outcomes suggest a window of opportunity at a young age for intervention to induce remission of peanut allergy.
Funding: National Institute of Allergy and Infectious Disease, Immune Tolerance Network.
Competing Interests: Declaration of interests SMJ reports grants from NIH-NIAID, Food Allergy Research & Education (FARE), Aimmune Therapeutic, DBV Technologies, Astellas, Sanofi, Regeneron, and Genentech; and personal fees from FARE, EMMES Corporation, and Aimmune Therapeutics. EHK reports personal fees from DBV Technologies, Aimmune Therapeutics, AllerGenis, Ukko, Vibrant America, Allakos, Kenota Health, and Duke Clinical Research Institute; and grants from FARE and the Wallace Research Foundation. KCN reports grants from NIAID, National Heart, Lung, and Blood Institute, National Institute of Environmental Health Sciences, and FARE; other fees from World Allergy Organization and Cour Pharma; other support from Before Brands, Alladapt, Latitude, IgGenix, Immune Tolerance Network (ITN), and NIH clinical research centres; and pending patent applications for inhibition of allergic reaction to peanut allergen using an IL-33 inhibitor (62/647,389), special oral formula for decreasing food allergy risk and treatment for food allergy (62/119,014), basophil activation based diagnostic allergy test (S10-392), granulocyte-based methods for detecting and monitoring immune system disorders (12/686,121), methods and assays for detecting and quantifying pure subpopulations of white blood cells in immune system disorders (12/610,940), mixed allergen compositions and methods for using the same (10/064,936), and microfluidic device and diagnostic methods for allergy testing based on detection of basophil activation (62/767,444). AN-W reports grants from NIH-NIAID, DBV Technologies, Astellas Pharma, and FARE; and grants and personal fees from Nestlé and Nutricia. RAW reports grants from NIAID, Aimmune, Astellas, DBV Technologies, Genentech, Regeneron, and Sanofi; and personal fees from UpToDate. HAS receives funding to his institution for grants from NIH-NIAID; consulting fees from DBV Technologies, N-Fold Therapeutics, and Siolta; and stock options from DBV Technologies and N-Fold Therapeutics. AMS reports grants from NIAID-ITN, FARE, Aimmune, DBV Technologies, Astellas, Sanofi, Regeneron, and Genentech; and personal fees from DBV Technologies. JW reports grants from NIAID and personal fees from DBV Technologies, ALK Abello, Genentech, and UpToDate. SBS reports grants from NIAID, Regeneron, DBV Technologies, Aimmune, Novartis, and Sanofi; and personal fees from AstraZeneca. MK reports grants from NIH and Department of Defence. JJ reports grants from NIAID. KS reports grants from NIH-NIAID. DCB reports grants from NIH-NIAID. HC reports grants from NIH-NIAID. DL reports grants from NIH-NIAID. All other authors declare no competing interests.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
التعليقات: Comment in: Lancet. 2022 Jan 22;399(10322):336-337. doi: 10.1016/S0140-6736(22)00088-5. (PMID: 35065770)
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معلومات مُعتمدة: UL1 TR001111 United States TR NCATS NIH HHS; UM1 AI109565 United States AI NIAID NIH HHS; UM2 AI117870 United States AI NIAID NIH HHS; UL1 TR002489 United States TR NCATS NIH HHS; UL1 TR003107 United States TR NCATS NIH HHS; UL1 TR003142 United States TR NCATS NIH HHS; UL1 TR000424 United States TR NCATS NIH HHS; UL1 TR000067 United States TR NCATS NIH HHS
سلسلة جزيئية: ClinicalTrials.gov NCT03345160
المشرفين على المادة: 0 (Allergens)
تواريخ الأحداث: Date Created: 20220123 Date Completed: 20220209 Latest Revision: 20240709
رمز التحديث: 20240709
مُعرف محوري في PubMed: PMC9119642
DOI: 10.1016/S0140-6736(21)02390-4
PMID: 35065784
قاعدة البيانات: MEDLINE
الوصف
تدمد:1474-547X
DOI:10.1016/S0140-6736(21)02390-4