Treatment of Multifood Allergy With Omalizumab or Multiallergen Oral Immunotherapy: A Randomized Clinical Trial

Food allergy is common, affecting up to 8% to 10% of children and adults. Treatment options include oral immunotherapy (OIT) and omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody.

To compare omalizumab with OIT for the treatment of patients with multifood allergy.

This was a double-blind, placebo-controlled, randomized clinical trial comparing omalizumab with omalizumab-facilitated multiallergen OIT (MOIT) in participants who completed stage 1 of the Omalizumab as Monotherapy and as Adjunct Therapy to Multiallergen OIT in Children and Adults With Food Allergy (OUTMATCH) trial, which led to the approval of omalizumab. The setting comprised 10 academic centers across the US. Included in this analysis were individuals aged 1 to 55 years with an allergy to peanuts and at least 2 other foods (milk, eggs, wheat, cashews, hazelnuts, walnuts). Eligibility was based on oral food challenge thresholds, requiring dose-limiting symptoms to cumulative doses of 144 mg or less of protein for peanuts and 444 mg or less for nonpeanut allergens. Data were analyzed from October 2024 to February 2026.

Participants were randomized to receive MOIT with placebo omalizumab or omalizumab with placebo MOIT. All received 16 weeks of open-label omalizumab; at week 8, active or placebo MOIT was initiated and escalated to goal doses of 1000 mg per food. At week 16, participants transitioned to blinded omalizumab or placebo injections for 44 weeks.

The primary end point was cumulative tolerated dose (CTD) of 4044 mg or greater for all 3 foods. Predefined secondary end points included CTDs of 1044, 2044, 4044, 6044, or 8044 mg for 1, 2, or all 3 foods.

A total of 117 participants (median [IQR] age, 7 [1-29] years; 64 male [55%]) were randomized to receive active MOIT (n = 58) or active omalizumab (n = 59). A total of 30 participants (51%) receiving active MOIT and 51 (88%) receiving active omalizumab completed the study. In the intention-to-treat (ITT) analysis, omalizumab was superior to MOIT (21 of 58 [36%] vs 11 of 59 [19%]; odds ratio, 2.6; 95% CI, 1.1-6.3; P = .03), with no differences in per-protocol analyses. Omalizumab superiority for CTDs of 4044 mg or greater was also demonstrated for 2 or more foods and for several individual foods. More participants taking active MOIT experienced adverse events (serious adverse events in 18 of 59 [31%] vs 0%; events leading to discontinuation in 13 of 59 [22%] vs 0%; events treated with epinephrine (22 of 59 [37%] vs 4 of 58 [7%]).

Although the ITT analysis found a higher rate of treatment success in those receiving omalizumab compared with MOIT, results suggest that the difference was largely driven by the high rate of study discontinuation in the participants treated with MOIT, mostly related to adverse events.