Anti-IgE Treatment with Oral Immunotherapy in Multifood Allergic Participants: Results of a Randomized, Double-blinded Control Trial

BACKGROUND: Despite progress in single food oral immunotherapy (OIT), there is little evidence concerning the safety and efficacy of treating individuals with multiple food (multifood) allergies. We conducted a pilot study testing whether anti-IgE (omalizumab) combined with multifood OIT benefitted multifood allergic patients. METHODS: In this blinded, phase 2 clinical trial conducted at Stanford University, 48 participants, aged 4-15 years, with multifood allergies validated by double-blind, placebo-controlled food challenges (DBPCFCs) to their offending foods were block randomized (3:1) to receive multifood OIT to 2-5 foods, together with omalizumab (n=36) or placebo (n=12). Omalizumab or placebo was administered subcutaneously for 16 weeks with OIT starting at week 8; omalizumab or placebo was stopped 20 weeks before exit DBPCFCs (week 36) to determine the primary endpoint: the proportion of participants who passed DBPCFCs to at least 2 of their offending foods. This completed trial is registered with ClinicalTrials.gov, . FINDINGS: At week 36, a significantly greater proportion of the omalizumab (30/36, 83%) vs. placebo (4/12, 33%) participants passed DBPCFCs to 2 g protein for ≥ 2 of their offending foods (odds ratio (OR): 10, 95% confidence interval (CI): 1·8, 58·3, P=0·004). The same individuals also tolerated 4 g protein of ≥ 2 foods (secondary endpoint, P=0·004). A greater proportion of omalizumab (13/17, 77%) vs. placebo (0/5, 0%) participants passed a DBPCFC to 2 g protein for ≥ 4 of their offending foods (OR: 33, 95% CI: 1·9, ∞, P=0·01). All participants completed the study. There were no serious or severe (≥ grade 3) adverse events. INTERPRETATION: In multifood allergic patients, omalizumab improves the efficacy of multifood OIT and enables safe and rapid desensitization. FUNDING: NIH U19 AADCRC and Opportunity Fund, Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Simons Foundation, Myra Reinhard Foundation, FARE Center of Excellence, Department of Pathology, and Department of Pediatrics, Stanford University.