Rasika Mathias, PhD: Detailing the LEAP Study

Data from 3 peanut oral immunotherapy (OI) trials supported the hypothesis that age, baseline characteristics and human leukocyte antigen (HLA) genetics may support the mechanism of antigen recognition fundamental to driving immune responses related to allergy protection and risk.

The LEAP study, which utilized findings from the POISED and IMPACT studies, was presented this weekend at the American Academy of Allergy, Asthma & Immunology Annual Meeting (AAAAI) 2022.

In an interview with HCPLive, Rasika Mathias, PhD, Division of Allergy and Immunology at Johns Hopkins University, spoke of the strength of the LEAP study and the association between the HLA allele and peanut allergy.

“When we think about genetics of peanut allergy and food allergy in general, the environment plays such a critical role that we've sort of been hampered a little in prior genetic studies for food allergy and peanut allergy in that the environments not adequately measured or included in these genetic evaluations,” Mathias said. “So, LEAP has just been a phenomenal opportunity, because it's a clinical trial setting.”

In the consumption arm of the LEAP study, the HLA locus was considered a risk factor for peanut allergy. When Mathias and colleagues considered this particular allele in the avoidance group, they found it was also related to peanut allergy risk in participants in that group as well.

“The HLA story here for this particular allele is not just a general peanut protein presentation piece, but really it's specific for the Rh2 component,” Mathias said. “We were able to validate that with sort of this linear expansion and epitope spreading to Rh2 specifically. Without leap, I don't know that we'd be in this particular discovery.”

With the data they had on the association of HLA and peanut allergy, Mathias and investigators then turned to the POISED and IMPACT studies to determine if individuals who had carrier status responded better to peanut intervention methods.

“In both the clinical trials, we see some really strong evidence that that may indeed be true,” Mathias said. “In POISED, the carriers are more likely to develop sustained unresponsiveness as opposed to the non-carriers, but we also see this for tolerance. In IMPACT, we see it quite prominently for desensitization. That odds ratio for protective is above 5, which is really quite compelling, right? It's a pretty strong effect that you go on to being desensitized much better if you're a carrier.”

Considering the 2 oral immunotherapy trials featured pediatric patients populations, with IMPACT specifically including children 48 month and younger, Mathias noted that investigators are continuing to determine if age plays a role in peanut allergy risk and sensitization.

“I think there's promise for us to start to build a deeper interrogation on genetics both from a food allergy risk perspective to identify those that are potentially at the greatest risk for allergy and therefore earlier interventions, but also modeling these genetics in response to it and potentially evaluating across different kinds of immunotherapy even beyond oral could be a great model for us to follow up,” Mathias said.