The Risk Reduction of Accidental Exposure-Related Systemic Allergic Reactions Extrapolated Based on Food Challenge Data After 1 Year of Peanut Oral Immunotherapy

Yu, Shengsheng; Smith, Alex; Hass, Steve; Wu, Eric; Chai, Xinglei; Zhou, Jenny; Ayyagari, Rajeev; Liu, Jun S.; Robison, Dan; Donelson, Sarah M.; Tilles, Stephen

INTRODUCTION: The phase 3 trial PALISADE, comparing peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) oral immunotherapy versus placebo in peanut-allergic children, reported that a significantly higher percentage of PTAH-treated participants tolerated higher doses of peanut protein after 1 year of treatment. This study used PALISADE data to estimate the reduction in the risk of systemic allergic reaction (SAR) after accidental exposure following 1 year of PTAH treatment. METHODS: Participants (aged 4–17 years) enrolled in PALISADE were included. Parametric interval-censoring survival analysis with the maximum likelihood estimation was used to construct a real-world distribution of peanut protein exposure using lifetime SAR history and highest tolerated dose (HTD) from a double-blind, placebo-controlled food challenge conducted at baseline. The SAR risk reduction was extrapolated using the exposure distribution and the HTD were collected at baseline and trial exit for PTAH- and placebo-treated participants. RESULTS: Assuming a maximum peanut protein intake of 1500 mg, participants were estimated to have < 1% probability of ingesting > 0.01 mg during daily life. The mean annual SAR risk at trial entry was 9.25–9.98%. At trial exit, the relative SAR risk reduction following accidental exposure was 94.9% for PTAH versus 6.4% for placebo. For PTAH-treated participants with exit HTD of 600 or 1000 mg without dose-limiting symptoms, the SAR risk reduction increased to 97.2%. The result was consistent in the sensitivity analysis across different parametric distributions. CONCLUSION: Oral immunotherapy with PTAH is expected to result in a substantially greater reduction in risk of SAR following accidental exposure compared to placebo among children with peanut allergy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12325-021-01843-2.