Early introduction of peanut reduces peanut allergy across risk groups in pooled and causal inference analyses.

Kirsty Logan, Henry T Bahnson, Alyssa Ylescupidez, Kirsten Beyer, Johanna Bellach, Dianne E Campbell, Joanna Craven, George Du Toit, E N Clare Mills, Michael R Perkin, Graham Roberts, Ronald van Ree, Gideon Lack

Journal: Allergy 2023;78(5):1307-1318

PMID: 36435990

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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.

Address: Department of Women and Children's Health, School of Life Course and Population Sciences, King's College London, London, UK.; Immune Tolerance Network, Benaroya Research Institute, Seattle, Washington, USA.; Charité Universitätsmedizin Berlin, Berlin, Germany.; Children's Hospital at Westmead, Westmead, New South Wales, Australia.; School of Biological Sciences, Division of Infection, Immunity and Respiratory Medicine, Manchester Academic Health Science Centre, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK.; The Population Health Research Institute, St George's University of London, London, UK.; University of Southampton and Southampton NIHR Biomedical Research Centre, Southampton, UK.; Departments of Experimental Immunology and of Otorhinolaryngology, Amsterdam University Medical Centers, Amsterdam, Netherlands.

DOI: 10.1111/all.15597