Target maintenance dose for peanut OIT is 300 mg protein (or less): Pros and cons
Authors: Julia Upton, Arnon Elizur
Journal: Allergy (2024)

The threshold increase provided by a maintenance dose of oral immunotherapy (OIT) is higher than the administered dose and is related to time and dose. High maintenance doses do raise the threshold higher than low doses, but low doses can provide a significant threshold increase. In the POISED study1 including participants aged from 7 to 55 years, maintenance was dropped to from 4000 to 300 mg peanut protein (PP) because it was difficult to persistently consume 4000 mg PP daily. Almost a year later, 37% could still tolerate 4000 mg PP. Such a level of desensitization may be achieved with low maintenance doses by most patients, when we consider subpopulations, such as preschoolers. For example, in a study by Vickery et al.2 a maintenance dose of 300 or 3000 mg PP allowed a desensitization of up to 5000 mg PP in 81% of children (85% in the low-dose and 76% in the high-dose group). Oral immunotherapy may not need to be increased above initially tolerated doses to be effective. Blumchen et al.3 demonstrated that only 125 mg PP provided significant desensitization even for children with initially higher eliciting doses. The POISED study1 also showed that even when patients continue a maintenance dose of 4000 mg PP, peanut allergy is persistent for most people suggesting that long-term routine ingestion is essential for ongoing protection. Low doses may facilitate compliance and reduce the burden of OIT. Extended time on low doses may mitigate side effects. The highest rate of home epinephrine use is in the week after an updose versus the 4th week after as well as during the early updoses (<500 mg PP) versus later higher doses.4 Side effects reduced in POISED after maintenance dosing was changed from 4000 to 300 mg PP. In summary, desensitization to multiples of the maintenance dose occurs for many children and some adults over time. OIT is not typically curative for older children and adults. The OIT dose may not need to exceed the initial tolerated dose. Maintenance with lower doses may allow OIT to be less demanding, be related to less allergic reactions, and thereby reduce barriers to treatment and compliance. A randomized controlled trial of OIT maintenance doses of 30 and 300 mg PP examining efficacy, side effects, and QOL is ongoing.5 To determine the optimal maintenance dose of OIT, there are three factors we need to consider; efficacy, safety, and QOL. Efficacy – the Vickery study demonstrated a comparable high efficacy for both 300 and 3000 mg PP maintenance dose in preschoolers.2 However, actual efficacy might be lower, as most participants were <24 months old, when ~20% spontaneous resolution of peanut allergy is expected. In older patients,1 reducing the maintenance dose from 4000 to 300 mg PP led to a significant reduction in desensitization rates over ~1 year and only 37% could tolerate a cumulative dose of ≥900 mg. Safety—most severe reactions in OIT occur during the initial stages of treatment and to low doses.4 Moreover, in the Vickery study, moderate–severe reactions were significantly more frequent in the low dose compared to the high-dose group.2 It seems, therefore, that a low dose would not significantly reduce adverse reactions. QOL—most patients undergoing OIT view the regular dose as a medicine they must take. A low maintenance dose would likely improve compliance. Such a dose is estimated to provide 95%–99% risk reduction when eating packaged foods contaminated with the allergen, or when eating in restaurants with brief cleaning of utensils6 and can provide sustained protection even in the most unimaginable situations.7 However, if utensils in restaurants are not properly cleaned, the risk reduction of a 300 mg maintenance dose falls by only 63%–91%.6 This might explain why a low maintenance dose (buffer) does not reduce patients' pretherapy anxiety.8 While patients do not want to deliberately eat the allergenic foods, they want to be able to eat outside without constantly having to inquire about allergen content. A low maintenance dose might fit patients with certain comorbidities (i.e., difficult to control asthma) or during specific scenarios (i.e., national crisis),9 but most patients would benefit from a high maintenance dose. A 1200 mg protein maintenance dose might be optimal as it was shown to improve compliance, while enabling free consumption following peanut OIT.10 JU reports research support/grants from Novartis, Regeneron, Sanofi, ALK Abello, DBV Technologies, CIHR, SickKids Food Allergy and Anaphylaxis Program; fees from Pfizer, ALK Abello, Bausch Health, Astra Zeneca, Pharming; she serves as an Associate Editor for Allergy Asthma and Clinical Immunology, is on the Board of Directors of Canadian Society of Allergy and Clinical Immunology, and the Healthcare Advisory Board of Food Allergy Canada, all outside the submitted work. AE does not have any conflicts of interest to disclose.