Omalizumab demonstrated superior efficacy to multiallergen oral immunotherapy (MOIT) for multifood allergy in the intention-to-treat analysis of the OUTMATCH stage 2 randomized clinical trial. However, the advantage narrowed once accounting for treatment discontinuation.¹
Omalizumab (Xolair) received US Food & Drug Administration (FDA) approval in 2024 for reducing allergic reactions, including anaphylaxis, following accidental food exposure, and remains 1 of only 2 approved food allergy therapies alongside a peanut oral immunotherapy (OIT) product: Palforzia, which will be permanently discontinued on July 31, 2026.2,3
Despite widespread clinical use of non-FDA-approved multiallergen OIT formulations, no prior randomized trial had directly compared omalizumab with MOIT.¹ The OUTMATCH stage 2 trial addressed this gap across 10 US academic centers.¹
"There was a very low rate of dropouts in the omalizumab side," trial investigator Robert A. Wood, MD, professor of pediatrics, Johns Hopkins University School of Medicine, told HCPLive at the 2025 American Academy of Allergy, Asthma, & Immunology (AAAAI) meeting in San Diego.4
Omalizumab Efficacy in OUTMATCH Stage 2
OUTMATCH stage 2 enrolled 117 participants (median age, 7 [1-29] years; 64 male [55%]) with allergy to peanuts and ≥ 2 other foods among milk, eggs, wheat, cashews, hazelnuts, or walnuts.¹ Participants completed 16 weeks of open-label omalizumab before randomization to double-blind MOIT with placebo omalizumab or omalizumab with placebo MOIT, followed by 44 weeks of blinded treatment.¹ MOIT was escalated to a goal maintenance dose of 1000 mg per food.¹
The primary end point was cumulative tolerated dose (CTD) of 4044 mg or greater for all 3 foods at the end-of-treatment food challenge.¹ In the intention-to-treat population, omalizumab achieved success in 36% of participants compared with 19% of participants receiving MOIT (odds ratio [OR], 2.6; 95% CI, 1.1-6.3; P =.03).¹ The per-protocol analysis, limited to participants who completed the study, showed no significant difference between arms (OR, 1.2; 95% CI, 0.5-3.3; P =.66).¹
Omalizumab Safety Versus MOIT in Food Allergy
Superiority for omalizumab extended to CTDs of 4044 mg or greater for 2 or more foods (OR, 3.3; 95% CI, 1.5-7.3; P =.002) and for individual foods including peanut (OR, 4.3; 95% CI, 1.9-9.7; P <.001), milk (OR, 6.2; 95% CI, 1.4-27.6; P =.02), and egg (OR, 11.7; 95% CI, 1.9-70.2; P =.004).¹ At a lower threshold relevant to accidental exposure, 72% of participants on omalizumab tolerated 444 mg or more of all 3 allergens compared with 39% of participants on MOIT.¹
Safety findings favored omalizumab across every measured category.¹ Participants receiving MOIT experienced more serious adverse events (31% vs 0%), events leading to discontinuation (22% vs 0%), and events treated with epinephrine (37% vs 7%).¹ Anaphylaxis occurred in 27% of MOIT participants versus 2% in the omalizumab arm, and 3 cases of biopsy-confirmed eosinophilic esophagitis occurred only in the MOIT group.¹
Discontinuation reached 49% in the MOIT arm compared with 12% for omalizumab, and investigators attributed most withdrawals to MOIT-related adverse events rather than a true efficacy gap among treatment completers.¹ A post hoc subgroup analysis suggested participants reaching the full 3000-mg MOIT maintenance dose had greater success rates than those at lower doses (54% vs 24%; P =.13), though the comparison was underpowered.¹
The investigators called for further comparative and cost-benefit research to guide individualized selection between anti-IgE and OIT strategies for multifood allergy.¹
“…although the ITT analysis demonstrated higher rates of treatment success with omalizumab across numerous end points, this difference was largely driven by the high rate of MOIT-related adverse events and study discontinuations rather than a difference in efficacy among those who completed treatment,” investigators concluded. “Both omalizumab and omalizumab-facilitated MOIT represent viable treatment options, each with distinct risk-benefit profiles that must be weighed in the context of individual patient needs and preferences.”
References
Wood RA, Togias A, Burk CM, et al. Treatment of multifood allergy with omalizumab or multiallergen oral immunotherapy: a randomized clinical trial. JAMA Pediatr. Published online July 27, 2026. doi:10.1001/jamapediatrics.2026.2910
With Palforzia® Ending, What’s Next for Peanut Allergy Patients. Allergy & Asthma Network. Published February 19, 2026. Accessed July 28, 2026. https://allergyasthmanetwork.org/news/palforzia-discontinued/
