@article{0ca156604ee24fe897ff52c7a6a2a73e,
title = "Early introduction of peanut reduces peanut allergy across risk groups in pooled and causal inference analyses",
abstract = "Background: The Learning Early About Peanut allergy (LEAP) study has shown the effectiveness of early peanut introduction in prevention of peanut allergy (PA). In the Enquiring About Tolerance (EAT) study, a statistically significant reduction in PA was present only in per-protocol (PP) analyses, which can be subject to bias. Objective: The aim of this study was to combine individual-level data from the LEAP and EAT trials and provide robust evidence on the bias-corrected, causal effect of early peanut introduction. Method: As part of the European Union-funded iFAAM project, this pooled analysis of individual pediatric patient data combines and compares effectiveness and efficacy estimates of oral tolerance induction among different risk strata and analysis methods. Results: An intention-to-treat (ITT) analysis of pooled data showed a 75% reduction in PA (p <.0001) among children randomized to consume peanut from early infancy. A protective effect was present across all eczema severity groups, irrespective of enrollment sensitization to peanut, and across different ethnicities. Earlier age of introduction was associated with improved effectiveness of the intervention. In the pooled PP analysis, peanut consumption reduced the risk of PA by 98% (p <.0001). A causal inference analysis confirmed the strong PP effect (89% average treatment effect relative risk reduction p <.0001). A multivariable causal inference analysis approach estimated a large (100%) reduction in PA in children without eczema (p =.004). Conclusion: We demonstrate a significant reduction in PA with early peanut introduction in a large group of pooled, randomized participants. This significant reduction was demonstrated across all risk subgroups, including children with no eczema. Furthermore, our results point to increased efficacy of the intervention with earlier age of introduction.",
keywords = "causal inference analysis, early introduction, peanut allergy prevention",
author = "Kirsty Logan and Bahnson, {Henry T.} and Alyssa Ylescupidez and Kirsten Beyer and Johanna Bellach and Campbell, {Dianne E.} and Joanna Craven and {du Toit}, George and {Clare Mills}, {E. N.} and Perkin, {Michael R.} and Graham Roberts and {van Ree}, Ronald and Gideon Lack",
note = "Funding Information: The main components of this analysis were funded by the European Union (Integrated Approaches to Food Allergen and Allergy Risk Management (iFAAM), Grant Agreement No: 312147). The EAT Study was jointly funded by the UK Food Standards Agency (FSA, contract code T07051) and the Medical Research Council (MRC, grant MC_G1001205). Additionally, we would like to thank the Davis Foundation. The skin‐related aspects of the EAT study were supported by the UK National Institute for Health Research (NIHR). The LEAP Study was supported by grants from the National Institute of Allergy and Infectious Diseases (NO1‐AI‐15416, UM1AI109565 and HHSN272200800029C); Food Allergy Research and Education; the Medical Research Council and Asthma UK; the United Kingdom Department of Health, through a National Institute for Health Research comprehensive Biomedical Research Centre award to Guy's and St. Thomas's NHS Foundation Trust, in partnership with King's College London and King's College Hospital NHS Foundation Trust; the National Peanut Board; and the United Kingdom Food Standards Agency. Funding Information: HB reports grants from the National Institute of Allergy and Infectious Diseases (NIAID, NIH) and consulting fees from DBV Technologies, outside the submitted work. KB reports institutional grants from the European Union during the conduct of the study and lecture fees from Aimmune, Allergopharma, Bencard, Danone/Nutrica, Infectopharm, Meda Pharma/Mylan, Nestle, ThermoFisher as well as consulting fees from Aimmune, ALK, Bausch & Lomb, Bencard, Danone/Nutrica, DBV, Hipp, Hycor, Infectopharm, Mabylon, Meda Pharma/Mylan, Nestle, Novartis, outside the submitted work. DEC receives a part‐time salary from the DBV Technologies as VP Clinical Development and Medical Affairs, receives institutional funding from the National Health and Medical Research Council of Australia and is on the Advisory Board of AllerGenis. The BEAT study was supported by the Ilhan Food Allergy Foundation and the Children's Hospital at Westmead Allergy and Immunology Research Fund. GdT reports grants from the National Institute of Allergy and Infectious Diseases (NIAID, NIH), Food Allergy & Research Education (FARE), MRC & Asthma UK Centre, UK Dept of Health through NIHR, Action Medical Research and National Peanut Board. Scientific Advisory Board member Aimmune, investigator on pharma‐sponsored allergy studies (Aimmune and DBV Technologies), shareholder in DBV technologies, and scientific advisor to Aimmune, DBV and Novartis. ENM reports grants from European Union, during the conduct of the study; grants from Reacta Biotech Ltd, other from Reacta Biotech Ltd, outside the submitted work. In addition, ENM has a patent Patents pending and Founder shares in Reacta Biotech Ltd. GR reports a grant from the European Union during the conduct of the study. RvR reports grants from the Dutch Science Foundation, Health Holland and the European Commission, during the conduct of the study; consultancy for HAL Allergy BV, Citeq BV and Angany Inc., speaker's fees from HAL Allergy BV and ThermoFisher Scientific, outside the submitted work. GL reports grants from the National Institute of Allergy and Infectious Diseases (NIAID, NIH), Food Allergy & Research Education (FARE), MRC & Asthma UK Centre, UK Dept of Health through NIHR, National Peanut Board (NPB), UK Food Standards Agency (FSA), Action Medical Research, the Davis Foundation during the conduct of the study; shareholder in DBV Technologies and Mighty Mission Me, scientific advisor for Novartis, Sanofi‐Genyzme, Regeneron, ALK‐Abello, outside the submitted work. No other disclosures were reported. Publisher Copyright: {\textcopyright} 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.",
year = "2022",
doi = "https://doi.org/10.1111/all.15597",
language = "English",
journal = "Allergy: European Journal of Allergy and Clinical Immunology",
issn = "0105-4538",
publisher = "Wiley-Blackwell",
}