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Early age peanut oral immunotherapy is safe and effective at achieving desensitization in 27 pediatric patients with peanut allergy

Pediatric Allergy and Immunology2024Vol. 35(11), pp. e14273–e14273

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Jonathan A. Hemler, Samantha Minnicozzi, Anne Carey, Karen Braden, Kelly Boyd

Abstract

IgE-mediated food allergy continues to affect a large proportion of the population, approximately 8% of children, and has major impacts on quality of life.1 Peanut allergy affects 2% of all children and is the leading cause of emergency room visits for anaphylactic reactions among all food allergens.2 Only 20% of patients naturally outgrow peanut allergy over time.3, 4 For patients with confirmed peanut allergy despite early introduction, several studies show that peanut oral immunotherapy started early in life is safe and effective at desensitization5-7 and there is a potential “window of opportunity” to achieve disease remission.8 However, additional real-world clinical data are needed to demonstrate if these desirable outcomes are truly achievable with early age peanut oral immunotherapy (epOIT).9 This study examines both the effectiveness and safety of peanut OIT in children less than 3 years old at epOIT start in a real-world academic clinical setting and was approved under University of Virginia School of Medicine Approved Protocol (IRB #24604). Inclusion criteria for this study include children ages 6 months to less than 3 years old who were prospectively recruited into an epOIT cohort from October 2020 to October 2023 at the University of Virginia Pediatric Allergy clinic. A clinical history of physician-diagnosed peanut allergy plus a positive peanut skin prick test (≥3 mm above negative control) and/or serum-specific IgE (≥0.35 kU/L) OR no clinical history and a peanut skin prick test (SPT) ≥8 mm (based on current NIH guidelines).10 Children with a history of severe anaphylaxis defined as the need for ICU admission and/or neurological or cardiovascular compromise, or severe/unstable asthma were excluded. Children with an Arah2 value >100 kU/L were also excluded. After thoroughly discussing all potential side effects, including the risk of severe allergic reactions and eosinophilic esophagitis, and signing written informed consent, epOIT was initiated at a dose of 14 mg peanut protein per day during an initial dose escalation day. Patients returned to clinic every 2 weeks for up-dosing and observed for 1 h, following a standard protocol of 11 additional up-dose visits to a goal maintenance dose of 500 mg peanut protein daily. Patients were evaluated at each visit for any symptoms suggestive of eosinophilic esophagitis and allergic reactions. Families were instructed to give the dose at home at the same time each day, preferably 3 h before bedtime, avoid exercise for 3 h after dosing, halve the dose for up to 3 days during intercurrent febrile illness if needed, and to contact the clinic if they missed more than 3 days of dosing. If patients had undergone a peanut oral food challenge (OFC) and reacted, their OIT starting dose was adjusted to one step below the highest amount tolerated during the food challenge without symptoms, and up-dosing proceeded from that point. Store bought Original PB2 Powder® was used as the primary peanut protein vehicle mixed with a liquid or puree the child enjoyed eating (applesauce, yogurt, etc.) and doses measured out proportionally according to the protocol. Families were offered the opportunity to switch to an equivalent amount of Reese's Pieces® or Peanut Butter M&Ms®, if developmentally appropriate, once the seventh up-dose step (250 mg peanut protein) was achieved. After continuing maintenance dosing for at least 1 year, participants were repeat skin and serum IgE tested and underwent an OFC to 6000 mg peanut protein at the supervising allergist's discretion. One patient was excluded from starting epOIT due to an Arah2 value of 332 ku/L. A total of 30 patients were recruited into the epOIT protocol with a median age at enrollment of 14 months [IQR 10–22 months]. Baseline patient characteristics at epOIT start are reported in Table 1. Eight patients started peanut OIT following a failed peanut food challenge at one step below the highest tolerated amount without symptoms. Three patients dropped out during the build-up phase. Two were lost to follow-up due to one moving out of state and another unable to come to clinic every 2 weeks for up-dosing due to parental work obligations. One patient dropped out due to an allergic reaction consistent with anaphylaxis (hives, lip angioedema, and new-onset cough) to his starting OIT dose of 14 mg peanut protein at home. IM epinephrine was not administered, and they did not go to the emergency department. The remaining 27 patients all successfully achieved maintenance dosing, 90% of the cohort. EpOIT was overall very well-tolerated with over half of patients reporting no adverse events and 40% reporting hives or other rash only, managed with oral cetirizine or diphenhydramine (Table 2). After completion of at least 1 year of maintenance dosing, eight patients whose skin and serum testing had sufficiently decreased to a level deemed appropriate by the supervising allergist to attempt a peanut OFC, underwent challenge to a cumulative dose of 6000 mg peanut protein. All eight patients passed this challenge and were instructed to freely eat peanut in their diets ad lib. After 5 months of maintenance therapy, a ninth patient accidentally ate ~3000 mg of peanut protein (about 40 Reese's Pieces®) at home with no reaction; therefore, an exit OFC was not performed. There have been no reports of peanut allergy recurrence among these nine patients (Figure 1). No patients reported symptoms concerning for eosinophilic esophagitis, and none were referred for endoscopic evaluation. In this real-world, unblinded, prospective case series, epOIT was safe and highly effective at achieving desensitization with the vast majority of patients able to reach maintenance dosing with minimal adverse effects. Of note, the overall cohort is relatively young (median age of 14 months at time of epOIT start) compared to several prior studies in this age group, which may explain this outcome.8 Other possibilities include selection criteria favoring patients with less severe allergy; however, the study team did not intentionally select patients with clinical histories suggestive of this, and only excluded patients based on the exclusion criteria noted above. Interestingly, eight patients were able to successfully pass a peanut food challenge after at least 1 year of maintenance therapy. Table S1 compares median baseline skin and serum testing to testing at time of exit peanut OFC for these eight children who passed this challenge. Interestingly, the SPT demonstrated a highly statistically significant difference in size from baseline compared to exit OFC while serum peanut IgE, total IgE, and Arah2 values did not. This is likely because the serum values were relatively low to start with at epOIT initiation, as well as the small sample size. Our study has several weaknesses including being a single center, small real-world clinical case series and not a randomized, double-blind placebo-controlled clinical trial. The study also did not utilize double-blind placebo-controlled food challenges (DBPCFCs) as the gold standard evaluation for demonstrating changes in tolerated peanut protein dose thresholds. Sustained unresponsiveness was also not assessed due to not utilizing DBPCFCs. Despite these limitations, this study has several important implications. First, it adds to the existing literature that shows infant and preschool age epOIT is easy to perform in a real-world, busy clinical setting, and families are very compliant with this therapy. Second, young children undergoing epOIT experience minimal adverse effects during build-up and maintenance dosing, findings similar to other studies of peanut OIT completed in this age group.5-7 Lastly, approximately one-third of our cohort started on epOIT that reached maintenance dosing now tolerate peanut ad lib. This demonstrates the need for large multi-center placebo-controlled clinical trials enrolling young children that can help answer the crucial question of whether epOIT is potentially disease modifying. Jonathan Hemler: Writing – original draft; writing – review and editing; conceptualization; investigation; methodology; project administration; funding acquisition; data curation; supervision; formal analysis; validation. Samantha Minnicozzi: Writing – review and editing; investigation; conceptualization; supervision; methodology. Anne Carey: Investigation; conceptualization; methodology; writing – review and editing. Karen Braden: Conceptualization; investigation; methodology; writing – review and editing; supervision. Kelly Boyd: Methodology; conceptualization; investigation; writing – review and editing; formal analysis; data curation; validation. The authors would like to acknowledge Sierra Dinsmore, MA and Kassidy Knight, RN, BSN for their outstanding care of our peanut oral immunotherapy patients presented in this article. Dr. Hemler and Karen Braden receive funding from Food Allergy Research and Education (FARE), which supported this work. None. Research performed under University of Virginia School of Medicine Approved Protocol (IRB #24604). The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1111/pai.14273. Table S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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