# Improving Safety in Food Allergen-Specific Oral Immunotherapy
## 3 Food Allergen Immunotherapy
### Pennut Oral Immunotherapy  
Peanut allergy is a significant concern, particularly among children, due to its potential to cause severe and life-threatening reactions. It is estimated that the prevalence of allergic reactions to peanuts lies at around 2% [35]. These facts have led to allergen-specific immunotherapy for peanuts becoming the most researched approach for peanut allergy treatment and food allergen-specific immunotherapy in general [36]. Different OIT protocols vary in terms of the initial dose, the rate of dose escalation, and the maintenance dose [4]. Some protocols start with very low doses (e.g., 0.1 mg of peanut protein) and increase gradually [37; 38], while others begin with higher initial doses or an initial dose that is determined after performing OFC [39]. The rate of escalation can also vary, with some protocols increasing the dose weekly, every two weeks, or monthly. Maintenance doses are categorized into either low-dose or high-dose groups, with only one protocol utilizing an intermediate maintenance dose [40]. The comparison data between the peanut OIT studies are shown in Table 3.  
The first double-blind RCT on peanut allergy was conducted by [PERSON] in 2011, involving a small group of children with peanut allergies. All children treated with OIT achieved desensitization to a cumulative dose of 5 g of peanut protein, experiencing only mild clinical symptoms during the build-up phase. The patients with severe anaphylaxis were excluded from this trial [41]. In a STOP II study, RCT was performed in children 7-16 years with immediate reactions after peanut ingestion; this involved a positive double-blind placebo-controlled food challenge (DBPCFC) with a maintenance dose of 800 mg of peanut protein. The ARs in most participants were mild [39]. These first RCTs were conducted with peanut flour [37; 39; 41]. In addition to conventional food forms, commercially standardized food products were used for this purpose [42; 43; 44; 45]. \begin{table}
\begin{tabular}{l l l l l l l l l l} \hline \hline
**Reference** & **Design** & **Sample** & \begin{tabular}{l} **Participants** \\ **Characteristic** \\ \end{tabular}  & \begin{tabular}{l} **Form of** \\ **Allergen** \\ \end{tabular}  & **Duration** & \ \begin{tabular}{l} **Maintenance** \\ **Dose** \\ \end{tabular}  & **Efficacy** & **Safety** \\ \hline \multirow{4}{*}{ \begin{tabular}{} \end{tabular}  } & \multirow{4}{*}{RCT} & \multirow{4}{*}{146 (12-48 m)} & Positive & \multirow{4}{*}{12 months} & & \multirow{4}{*}{300 mg} & & AE: mild to moderate & 75.5\%, systemic 2\%, \\  & &  
\begin{table}
\begin{tabular}{l l l l l l l l l l} \hline \hline  
The study conducted by [PERSON] et al., two studies by [PERSON] et al., and a survey by [PERSON] used commercial products in studies, all with a maintenance dose of 300 mg [42; 43; 44; 45]. The ARC001 and PALISADE studies were conducted in patients positive for DBPCFC of 143 mg peanut protein and 100 mg peanut protein. ARs were high among the treatment group even though the rate of ARs between the treatment group and placebo group differed only regarding serious ARs, which were rare (4.3% vs. 0.8%) [42; 43]. The open-label follow-on studies conducted by [PERSON] et al. (ARC004) and [PERSON] et al. both used the same commercial product in a maintenance dose of 300 mg, but, in patients negative to DBPCFC, in a dose of 300 mg of peanut proteins [44; 45]. The study by [PERSON] randomized the patients according to the dosing schedule, showing that the rate of ARs was lower in patients using maintenance doses every day compared to the different maintenance dosing regimens. The prolonged exposure to the maintenance dose led to a decrease in ARs, still with significant immunomodulation and desensitization [44]. The IMPACT trial was performed with peanut flour and had a higher level of peanut protein in the maintenance dose, with 71% of patients developing desensitization, of whom 21% were SU. Peanut OIT in children younger than four years old was linked to increased desensitization and SU [38].