Using data from food challenges to inform management of food-allergic consumers: a systematic review with individual participant data meta-analysis

ABSTRACT: Background Eliciting doses (e.g. ED01 or ED05 values, the amount of allergen expected to cause objective symptoms in 1% and 5% of the allergic population) are increasingly used to inform allergen labelling and clinical management. These values are generated from food challenge, but the frequency of anaphylaxis to these low levels of allergen exposure and their reproducibility is unknown. Objective To determine (i) the rate of anaphylaxis to low level peanut exposure, and (ii) the reproducibility of reaction thresholds (and anaphylaxis) at food challenge. Methods Systematic review and individual participant data (IPD) meta-analysis of studies reporting ≥50 peanut-allergic individuals reacting to peanut at double-blind, placebo-controlled food challenges (DBPCFC), published between January 2010 and September 2020. Risk of bias was assessed using National Institute for Clinical Excellence methodological checklists. Results Nineteen studies were included (total 3151 participants, 534 who subsequently underwent a further peanut challenge). At IPD meta-analysis, 4.5% (95%CI 1.9-10.1%) of individuals reacted to ≤5mg peanut protein with anaphylaxis (moderate heterogeneity [I2=57%]). Intra-individual thresholds varied by up to 3-log, although this was limited to a ½-log change in 71.2% (95%CI 56.2-82.6%). 2.4% (95%CI 1.1-5.0%) of patients initially tolerated 5mg peanut protein but then reacted to this dose at subsequent challenge (low heterogeneity, I2=16%); none had anaphylaxis. Conclusion Around 5% of individuals reacting to an ED01 or ED05 level of exposure to peanut might have anaphylaxis to that dose. This equates to 1 and 6 anaphylaxis events per 2500 patients exposed to an ED01 or ED05 dose (respectively) in the broader peanut-allergic population.