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

Nandinee Patel, Daniel C Adelman, Katherine Anagnostou, Joseph L Baumert, W Marty Blom, Dianne E Campbell, R Sharon Chinthrajah, E N Clare Mills, Bushra Javed, Natasha Purington, Benjamin C Remington, Hugh A Sampson, Alexander D Smith, Ross A R Yarham, Paul J Turner

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Eliciting doses (EDs) (eg, ED01 or ED05 values, which are the amounts of allergen expected to cause objective symptoms in 1% and 5% of the population with an allergy, respectively) are increasingly being used to inform allergen labeling and clinical management. These values are generated from food challenge, but the frequency of anaphylaxis in response to these low levels of allergen exposure and their reproducibility are unknown.

OBJECTIVE: Our aim was to determine (1) the rate of anaphylaxis in response to low-level peanut exposure and (2) the reproducibility of reaction thresholds (and anaphylaxis) at food challenge.

METHODS: We conducted a systematic review and individual participant data meta-analysis of studies that reported at least 50 individuals with peanut allergy reacting to peanut at double-blind, placebo-controlled food challenge (DBPCFC) and were published between January 2010 and September 2020. Risk of bias was assessed by using National Institute for Clinical Excellence methodologic checklists.

RESULTS: A total of 19 studies were included (covering a total of 3151 participants, 534 of whom subsequently underwent further peanut challenge). At individual participant data meta-analysis, 4.5% (95% CI, 1.9% to 10.1%) of individuals reacted to 5 mg or less of peanut protein with anaphylaxis (moderate heterogeneity [I2 = 57%]). Intraindividual thresholds varied by up to 3 logs, although this variation was limited to a half-log change in 71.2% (95% CI, 56.2% to 82.6%) of individuals. In all, 2.4% (95% CI, 1.1% to 5.0%) of patients initially tolerated 5 mg of peanut protein but then reacted to this dose at subsequent challenge (low heterogeneity [I2 = 16%]); none developed anaphylaxis.

CONCLUSION: Around 5% of individuals reacting to an ED01 or ED05 level of exposure to peanut might develop anaphylaxis in response 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 population of individuals with peanut allergy.

Original languageEnglish
Pages (from-to)2249-2262
JournalThe Journal of allergy and clinical immunology
Issue number6
Early online date9 Feb 2021
Publication statusPublished - 1 Jun 2021


  • Eliciting dose
  • oral food challenge
  • peanut allergy
  • precautionary allergen labeling
  • thresholds


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