Precision Allergy Thresholds With Accurate immunotherapy Selection -Clinical Core

Icahn School Of Medicine At Mount Sinai, New York NY

Investigators

Linked publications & trials

Abstract

SUMMARY - Clinical Core In the US, peanut allergy affects approximately 2.2% of children, 1.8% of adults, and can be potentially fatal, life-long, and has adverse impacts on quality of life. A commercial oral immunotherapy (OIT) for peanut allergy using low milligram doses has been FDA approved for children 4-17 years of age. This costly product was tested on children who reacted to a 143 mg cumulative dose of peanut or less (low threshold) during an oral food challenge (OFC) and aims for a maximum treatment dose of 300 mg, an amount similar to one large peanut kernel. Studies suggest that more than half of the peanut allergy population has a threshold above that which was used for testing the commercial peanut OIT product, a high threshold phenotype. Our current AADCRC has completed enrollment for a study evaluating OIT for this high threshold group where subjects are treated with home-measured peanut butter. Our preliminary results suggest that this is an easy-to-treat group with few side effects and high success rates, including persistent desensitization when therapy is interrupted. These observations inform a clinical need to determine Precise Allergy Thresholds With the purpose of Accurate immunotherapy Selection (PATHWAYS), which is the foundation for this Clinical Core. Determination of threshold allows personalized therapy for children with a low threshold to receive commercial OIT and those with a high threshold to receive home measured peanut at much lower expense. Importantly, we do not understand why some children have a difficult to treat phenotype, severe reactions, or a particular threshold, and we do not know why or how responses to immunotherapy differ across severity and threshold. Projects 1 (ROSETTA) and 2 (IMPALA) in our AADCRC will determine novel transcriptomic and immune processes across these phenotypes to characterize endotypes, elucidate mechanisms, inform precision care, and identify opportunities for novel therapeutics. Within the PATHWAYS Clinical Core, subjects who will benefit from threshold determination for clinical purposes will undergo double-blind, placebo-controlled OFCs with skin testing and serial blood sampling during the OFC for research purposes, along with determination of reaction severity and response to OIT treatment (given for clinical purposes off study). The PATHWAYS Clinical Core is designed to provide samples and data across the threshold and severity spectrum, for both primary and validation studies being undertaken in ROSETTA and IMPALA. We will build upon our stellar track record of successful biosampling in our current AADCRC, where we obtained blood at all time points in 97.5% of 310 OFCs at 100% of the required volume. The clinical data and biosamples from PATHWAYS will fuel the novel investigations of the ROSETTA and IMPALA research projects. Our integrated program will enrich mechanistic understandings, advance personalized medicine, and identify new therapeutic targets.