The first investigation of anti-IgE therapy for the management of FA was performed in a double-blind, randomized, dose-ranging (150, 300, or 450 mg of anti-IgE antibodies (TNX-901)) trial in 84 patients, 12 to 60 years of age, with a positive history of peanut allergy. Although the highest TNX-901 dose significantly improved clinical symptoms and increased the threshold dose for peanuts, 25% failed to develop a tolerance to peanuts, suggesting a wide treatment response variability [36]. A subsequent double-blinded, placebo-controlled study was started in children 6 years of age, but discontinued because of safety issues related to pre-omalizumab challenges [37]. An open-label study in 14 adults between 18 and 50 years of age showed a significant increase in the mean tolerated dose of peanut protein (from 80 mg to 5080 mg) after 6 months of omalizumab; however, the administration of antihistamines and epinephrine was required in 10 of the 14 enrolled subjects [38]. To increase the safety of immunotherapy and possibly enhance tolerance development, a combination of anti-IgE therapy and FA-AIT was investigated. Two small double-blind, placebo-controlled food challenge trials in patients (age, 7–25 years) with a peanut [39] or cow’s milk [40] allergy were conducted by using omalizumab in combination with rapid oral food desensitization. During a washout period, participants were generally treated with omalizumab for 2 to 5 months and subsequently continued on treatment until a maintenance dose of OIT was achieved. In the first study, 92% of patients tolerated the challenge, but 46% of children experienced moderate to severe adverse events [39]. In the second trial, 9 out of 11 patients were able to complete dose escalation and only 1.8% of subjects still showed reactions requiring epinephrine [40]. Subsequently, a phase one clinical trial was designed in 25 participants (median age 7 years) with multiple FA. Participants were receiving OIT for up to 5 allergens simultaneously with omalizumab. Anti-IgE therapy was administered for 8 weeks prior to and 8 weeks following the initiation of the OIT protocol. Adverse reactions were reported in 5.3% of subjects. Additionally, 94% of reactions were mild and only one subject experienced a severe reaction requiring epinephrine [23]. Following this, a phase one double-blind, placebo-controlled food challenges study, enrolling patients aged 4–15 years with multiple FA, confirmed that adjunctive omalizumab with OIT provided a safe and rapid desensitization with a lower median rate of adverse events (27% vs. 68%). Interestingly, no serious or severe adverse events were recorded [41].