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

• Published in: Allergy (Copenhagen) Vol. 78; no. 5; pp. 1307 - 1318
• Main Authors: Logan, Kirsty, Bahnson, Henry T., Ylescupidez, Alyssa, Beyer, Kirsten, Bellach, Johanna, Campbell, Dianne E., Craven, Joanna, Du Toit, George, Clare Mills, E. N., Perkin, Michael R., Roberts, Graham, Ree, Ronald, Lack, Gideon
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.05.2023; John Wiley and Sons Inc
• Subjects: Allergens; Allergies; Arachis; causal inference analysis; Child; Children; Clinical trials; early introduction; Eczema; Food allergies; Humans; hypersensitivity; infancy; Infant; Original; ORIGINAL ARTICLES; patients; peanut allergy prevention; Peanut Hypersensitivity - epidemiology; Peanut Hypersensitivity - prevention & control; peanuts; Pediatrics; protective effect; relative risk; Risk Factors; Risk groups; risk reduction; Statistical analysis; causal inference analysis; early introduction; peanut allergy prevention
• ISSN: 0105-4538; 1398-9995; 1398-9995
• DOI: 10.1111/all.15597

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. An integrated meta‐analysis employing both LEAP (high risk) and EAT (normal risk) individual patient data shows that early introduction of peanut in infancy prevents the development of peanut allergy regardless of presence or severity of eczema, ethnicity and sensitization to peanut. Earlier introduction of peanut before 6 months of age is more effective than later introduction in the prevention of peanut allergy. Causal inference methods accurately estimated the efficacy of this strategy while addressing the problems of poor adherence in the intention‐to‐treat analyses and biases in the per‐protocol analyses.Abbreviations: EAT, enquiring about tolerance; ITT, intention to treat; LEAP, learning early about allergy; PP, per protocol