# Improving Safety in Food Allergen-Specific Oral Immunotherapy
## 4 Discussion
The POSEIDON and IMPACT studies have indicated that younger intervention ages correlate with increased tolerability, suggesting that the age of OIT initiation may be a key factor in enhancing safety [38; 46]. A further potential modification to the food oral immunotherapy (F-OIT) protocol involves reducing the maintenance dose of the offending food. Evidence suggests that low-dose OIT can suppress pro-allergic cytokines and basophil activation in children [93]. Reduced maintenance doses have been effectively utilized in single-food studies, such as those involving peanuts, cow's milk, and eggs, demonstrating successful desensitization and sustained unresponsiveness, albeit with limited evidence. In children with severe cow's milk allergy (CMA), transitioning to a lower maintenance dose has resulted in enhanced safety for OIT, and similar outcomes have been observed with low-dose OIT in pediatric patients with peanut allergies [14; 15; 44; 45]. Administering lower maintenance doses could potentially prevent OIT-induced eosinophilic esophagagitis (EoE) and EoE-like conditions associated with OIT, although the supporting evidence is limited. The application of low-dose OIT is currently being explored for multiple food allergens [94]. Maintaining a low dose over an extended duration has further improved patient safety and minimized the occurrence of allergic reactions [34; 44]. Cross-comparisons of daily dosing with various dosing regimens reveal that daily dosing exhibits a superior safety profile [30; 34; 44]. Moreover, OIT utilizing less allergenic food forms, such as baked milk or eggs, may also enhance safety, albeit potentially at the expense of efficacy [20; 31]. For patients with severe food allergies, the safety of OIT can be further enhanced through the utilization of adjuvants, with omalizumab emerging as the most promising candidate among these adjunct therapies. The role of other forms of biologic therapy in improving safety during OIT remains a subject of debate. Despite the observation that children with food allergies may exhibit gut dysbiosis and lower serum levels of vitamin D3 compared to their healthy peers, the use of probiotics and vitamin D3 as adjuncts in OIT has not yielded satisfactory results to date [89; 95]. Collaboration among experts is essential to establishing universal access to validated protocols and standardized products. There remains a pressing need for high-quality evidence regarding optimal maintenance dose frequency and duration, appropriate initiation ages that correlate with individual patient profiles, and the effective use of biologic's tailored to patient characteristics, alongside long-term follow-up and cost-effectiveness analysis. Our proposed measures to enhance the safety of OIT are outlined in Scheme 1. In this review, we aimed to provide a concise overview of the safety of various OIT protocols documented thus far; however, certain limitations must be acknowledged. Notably, there is a dearth of placebo-controlled randomized controlled trials (RCTs), which complicates the estimation of placebo effects in terms of safety, particularly when assessing subjective symptoms reported during OIT. Furthermore, most existing studies primarily focus on the short-term effects of OIT. Additional follow-up investigations beyond the completion of OIT are warranted to evaluate long-term safety, particularly in light of the influence of co-factors such as exercise and infections. The absence of a standardized OIT protocol, coupled with significant disparities among protocols, renders comparisons of efficacy and safety challenging. Additionally, the lack of a uniform methodology for reporting allergic reactions across studies further complicates comparisons. Despite the current limitations, OIT remains a promising approach for managing pediatric food allergies. By optimizing protocols-- tailoring dose, duration, and adjunct therapy to individual patients--we can move toward safer, more effective treatments.