A new phase II trial, dubbed COMBINE, suggests that a sequential treatment of biologics may help improve the tolerability of multi-allergen oral immunotherapy (mOIT), particularly by reducing gastrointestinal (GI) side effects that often lead patients to abandon treatment. Specifically, adding dupilumab (Dupixent) after an initial course of omalizumab (Xolair) was associated with fewer GI symptoms, though it did not significantly improve the study’s primary long-term efficacy endpoint.
The study, presented at the American Academy of Allergy, Asthma & Immunology annual meeting, focused on the “tolerability barriers” that limit mOIT success. GI symptoms—such as vomiting, abdominal pain, and diarrhea—are a common challenge during immunotherapy. In this trial, GI symptoms dropped to 0.013 events per OIT dose with dupilumab, compared to 0.033 in the placebo group, suggesting that dupilumab’s IL-4/IL-13 blockade may help patients better tolerate treatment.
The multicenter trial involved 108 patients with an average age of 12.4 years, all of whom had a confirmed peanut allergy and at least one additional food allergy. Participants were divided into three groups to evaluate different combinations of omalizumab, dupilumab, and placebo. The primary endpoint was the ability to tolerate a peanut protein challenge at week 44, after biologic treatments had been discontinued.
Regarding efficacy, results were mixed. During the active desensitization phase at week 32, patients receiving the second biologic were more likely to tolerate higher doses of allergens (92% vs 63%). However, this advantage diminished after treatment stopped, and the week-44 primary endpoint was only numerically improved with dupilumab, without reaching statistical significance. As Tina Sindher, MD, noted, the benefits appeared to “equalize” once treatment was withdrawn.
Safety and tolerability findings stood out. Adverse event–related withdrawals occurred in the placebo group but not among those receiving dupilumab, reinforcing its potential role in helping patients stay on therapy. Researchers noted that a subset of patients—possibly around 20%—experience persistent GI symptoms during OIT, and these individuals may benefit most from additional biologic support.
Cecilia Berin, PhD, highlighted that elevated levels of type 2 cytokines such as IL-4 and IL-13 have been linked to treatment failure, suggesting a path toward more personalized care. Identifying “high-type 2” patients early could help clinicians determine who is most likely to benefit from adding dupilumab to their treatment regimen.
While the study was limited by its sample size and lack of statistical significance for the primary endpoint, researchers remain optimistic. The findings suggest that while dupilumab may not be a universal solution for improving long-term outcomes, it could play an important role in making multi-allergen immunotherapy more tolerable—and therefore more achievable—for certain patients.
