Dupilumab Improves Desensitization Outcomes in OIT, With Sayantani Sindher, MD

The COMBINE trial, presented as a late breaker at the 2026 American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting in Philadelphia, found that adding dupilumab to omalizumab-facilitated multi-allergen oral immunotherapy (OIT) improved desensitization outcomes and reduced gastrointestinal adverse events.

However, it did not significantly increase sustained unresponsiveness. This begs the question: How should clinicians counsel patients about expectations for desensitization versus sustained responsiveness?

“I'm always trying to figure out how to apply sustained unresponsiveness data to the patient sitting in front of me,” investigator Sayantani Sindher, MD, clinical associate professor of medicine at Stanford University, told HCPLive during the meeting. “When you have a patient in front of you as an individual, it's really hard to [figure] out, ‘Okay, are you going to be someone who will achieve sustained unresponsiveness versus not? ‘ In my outpatient care, I don't take them off of [therapy for] a long period of time. If they do miss many days or months of treatment, I will bring them back in and do observed dosing to get them right back on track. Until we have biomarkers available that can predict sustained unresponsiveness, it is not something I'm able to readily apply in my outpatient clinical care practice.”

The randomized COMBINE trial enrolled 108 individuals with multiple food allergies (peanut plus 1 or 2 additional allergens) and investigated whether dupilumab could improve outcomes during omalizumab-assisted OIT. Participants first received omalizumab for 8 weeks, after which they received OIT with either dupilumab or placebo from weeks 8 through 32. All therapies were discontinued at week 32, and sustained unresponsiveness was evaluated at week 44 using double-blind, placebo-controlled food challenges.

Although the trial’s primary endpoint, sustained unresponsiveness to ≥1043 mg of peanut protein, was not statistically different between groups, results suggested potential benefits with dupilumab. Sustained unresponsiveness was achieved in 39% of patients receiving omalizumab plus OIT and 55% of those receiving dupilumab plus OIT (P =.16).

Secondary findings showed improvements in desensitization and tolerability with the addition of dupilumab. By week 32, 92% of patients receiving dupilumab tolerated the highest tested allergen dose (4043 mg) during food challenge compared with 63% of those receiving OIT without dupilumab (adjusted P =.013). Investigators also reported fewer gastrointestinal symptoms and treatment withdrawals in the dupilumab group.

Despite encouraging signals, Sindher emphasized that translating combination biologic strategies into routine practice requires consideration of real-world factors such as insurance coverage and drug costs.

“In clinical trials, we have funding to obtain the drugs. In the outpatient world, it all goes through insurance, and access is a big deal,” Sindher said. “The cost of it is… something we have to think through before… we start using it.”

Future analyses of the COMBINE trial are exploring immune mechanisms underlying treatment responses, including assessments of B cells, T cells, and basophil activation. Sindher said these efforts may help identify patient subgroups most likely to benefit from combination biologic approaches and inform more personalized strategies for managing food allergy.

“What we need is a much better understanding of why it works,” Sindher said. “Who is the population it works best for, and also who is the population it doesn't work for? Once we have better predictive biomarkers or algorithms that help us phenotypically cluster these patients, it'll be really hard to know when to use these biologics…Many of our food allergic kids and adults also have many other atopic conditions [such as asthma, eczema, seasonal allergies, eosinophilic esophagitis] …Having different biologics approved for some of these indications that may also help for food allergy would really help us address multiple atopic conditions with just one drug.”

A relevant disclosure for Sindher includes Genentech USA.

References

1. Sindher S, Long A, Garcia-llorett M, et al. The addition of dupilumab enhances desensitization and reduces gastrointestinal symptoms in omalizumab-facilitated multi-allergen oral immunotherapy in the COMBINE trial. Journal of Allergy and Clinical Immunology. 2026;157(2):AB415. doi:https://doi.org/10.1016/j.jaci.2025.12.917

2. Sindher S. Dupilumab Reduces GI Symptoms During Multi-Allergen OIT, With Sayantani Sindher, MD. HCPLive. Accessed on March 12, 2026. Published on March 5, 2026. https://www.hcplive.com/view/dupilumab-reduces-gi-symptoms-multi-allergen-oit-sayantani-sindher-md