Treatment with omalizumab offers modest protection from allergic reactions to individuals with multiple food allergies, and baseline immunoglobulin E (Ig E) levels are associated with success, based on an exploratory analysis of data from the OUtMATCH study.

Results of OUtMATCH, a double-bind randomized controlled trial, showed significant improvements in food tolerance from baseline to 16-20 weeks after treatment with omalizumab, an anti-IgE antibody, according to R. Sharon Chinthrajah, MD, of Stanford University, Palo Alto, California, and colleagues. Omalizumab was approved by the FDA in February 2024 for the treatment of IgE-mediated food allergy in adults and children aged 1 year or older.

However, in the wake of the approval, better predictive markers beyond oral food challenges are needed to assess posttreatment response, the researchers wrote. The goal of the current study was to identify potential predictors and correlates of therapeutic response to omalizumab, they said.

In a new exploratory analysis, published inThe Journal of Allergy and Clinical Immunology, the researchers examined predictors of response after active omalizumab treatment for individuals with allergies to peanut and other foods including cashew, egg, milk, and walnut. Cumulative tolerated dose (CTD) was included as a continuous variable, as were CTDs of ≥ 444 mg and 1044 mg of allergen protein. These values differ from the original primary outcome data in the OUtMATCH study and more accurately represent accidental exposures in the real world, the researchers explained.

The researchers assessed 13 baseline variables as possible predictors of response, including demographic parameters such as weight, BMI, and presence or absence of other atopic disease; immune parameters such as total IgE, specific IgE, and skin prick test results; and omalizumab dosing and dosing frequency.

The association was expressed as a correlation coefficient (r value) and 

q value (a measure of P value that controls false discovery rate). The study population included 116 individuals with a mean age of 8 years.

Overall, in a multivariate analysis, only a higher total IgE at baseline was a significant predictor of a positive response to omalizumab treatment (for peanut cumulative targeted dose, the r value was 0.25 and the q value was 0.047). Omalizumab treatment every 2 weeks also was associated with higher peanut cumulative targeted dose outcomes in an analysis of peanut only.

No correlation was noted between treatment response and allergy history, allergen-specific IgE, skin prick test results, or basophil activation.

When stratified by multiple food allergies, individuals with allergies to both peanut and milk showed a positive response to omalizumab (r = 0.34; q = 0.003), but peanut allergy concurrent with cashew or walnut allergy was inversely correlated with omalizumab outcomes (r = -0.26; q = 0.042). Additionally, approximately 70% of individuals treated with omalizumab tolerated at least 444 mg and 1044 mg cumulative protein for peanut, egg, milk, and walnut. Fewer participants tolerated these levels of cashew (66% and 49%, respectively).

Although a higher baseline total IgE was the most consistent predictor of successful protection for peanut and other foods, the results should be interpreted with caution, and larger studies are needed to confirm total IgE’s value as a predictor, the researchers emphasized.

Total IgE levels could be used in practice to stratify patients and identify those most likely to succeed with omalizumab; however, total IgE levels fluctuate over time according to exposures and comorbid conditions, they noted. In addition, the results suggest that total IgE is the likely driver of the results for dosing frequency, rather than the reverse, as dosing frequency is generally a function of total IgE, they said.

Looking ahead, the results support the need for more reliable biomarkers to predict response to omalizumab, and the need for oral food challenges to confirm treatment response from higher-level allergen exposures, the researchers concluded.

In the Clinic

The current study provides an important evaluation of biomarkers that may predict response to omalizumab therapy in food-allergic patients, said Aikaterini Anagnostou, MD, director of the Food Immunotherapy Program at Texas Children’s Hospital, Houston, in an interview.

“The authors found that higher pretreatment total IgE levels were consistently associated with therapeutic success across multiple outcomes, whereas more traditional allergy biomarkers, such as skin-prick tests, allergen-specific IgE, and sIgE/tIgE ratios did not reliably differentiate responders from nonresponders,” said Anagnostou, who was not involved in the study.

“Notably, this pattern contrasts with findings from oral immunotherapy studies, where lower baseline total IgE has been associated with better outcomes, particularly sustained unresponsiveness and remission,” Anagnostou told Medscape Medical News. “Taken together, these observations could offer valuable guidance in clinical counseling by helping set expectations for various treatment options based on an individual’s baseline total IgE level,” she said.

The results also suggest the need to identify more patients who could benefit from omalizumab, said Anagnostou. “Patients with total IgE levels above 1850 IU/mL are currently excluded from omalizumab eligibility, yet these may be the individuals in whom the drug could be most effective,” she said. More research is needed to refine clinical understanding of these biomarkers and make progress towards truly personalized care for patients with food allergy, she added.

This study was funded by the National Institute of Allergy and Infectious Diseases, the National Center for Advancing Translational Sciences, the Claudia and Steve Stange Family Fund, Genentech, and Novartis. Chinthrajah disclosed grant support from the Consortium for Food Allergy Research, National Institute of Allergy and Infectious Disease, and Food Allergy Research & Education (FARE); she also disclosed serving as an advisor for Novartis, Intrommune Therapeutics, Phylaxis, Genentech, Latitude, RAPT, Blueprints Therapeutics, and Grow Happy. Chinthrajah also owns stock in Intrommune Therapeutics and Grow Happy. Anagnostou disclosed institutional funding from Novartis, AAFA, Aquestive, and ALK, as well as serving as an advisory board member for Novartis, Genentech, Bryn, ALK, ARS, Aquestive, and consultation/speaker fees for ALK, EPG Health, MJH, Adelphi, DBV Technologies, Genentech, Medscape, ARS, FARE, Innovation Horizons, and Stallergenes.