Omalizumab Aids Desensitization to Several Food Allergies

Veronica Hackethal, MD

February 28, 2014

People with multiple food allergies may become desensitized to them safely, using oral immunotherapy (OIT), and treatment with the asthma medication omalizumab (Xolair, Genentech Inc and Novartis Pharmaceuticals Corporation) could shorten this process.

Researchers from Stanford University in California report the results of 2 recent studies in articles published online in Allergy, Asthma & Clinical Immunology.

About 30% of food allergic children have multiple food allergies, according to the authors. OIT consists of administering small amounts of allergen, followed by escalating doses over time to induce desensitization.

The first study, published online January 15, by Philippe Bégin, MD, from the Allergy, Immunology, and Rheumatology Division, Stanford University, and colleagues was a proof-of-concept, single-site safety trial. Allergies were confirmed using skin prick tests, food-specific immunoglobulin E (IgE) levels, and double-blind placebo-controlled food challenges with peanut, other nut, sesame, dairy, and egg allergens. Participants with only peanut allergy received single-allergen mono-OIT, whereas those with multiple allergies received up to 5 allergens in a multi-OIT mix customized to their allergy profile. There were 3 phases: initial escalation day, home dosing with biweekly hospital visits for dose escalation to a goal of 4000 mg per allergen, and maintenance. Participants recorded home reactions in symptom diaries.

Of 40 total participants aged 4 to 46 years, 15 had peanut-only allergies and 25 had multiple allergies. There were no significant differences between groups in rates of reaction per dose (P = .31). The multi-OIT group reached maintenance at a median of 85 weeks, or 14 weeks later than the mono-OIT group (P < .005). Most reactions were mild, with abdominal pain being most frequent. Two participants from each group experienced severe reactions requiring epinephrine.

Limitations include the inability to prove tolerance, which requires that participants demonstrate nonresponsiveness on allergen challenge at an extended time after stopping their maintenance dose. The study was also limited by lack of randomization and by the inability to look at cross-reactivity in multiallergic participants.

"[T]his phase 1 study demonstrates that it is possible and feasible to test the effect of multi food allergen therapy simultaneously, rather than performing single immunotherapy in sequence for patients, a process that could take many years for patients who are multi-sensitized to food allergens," the authors conclude.

Omalizumab May Speed Desensitization

The second study, published online February 20, also by Dr. Bégin and colleagues, looked at shortening the time course of multi-OIT, using adjunctive treatment with omalizumab, an IgE immunomodulatory drug. Omalizumab likely increases the threshold for adverse reactions to food allergens, the authors explain, which could allow for higher starting doses as well as faster dose escalation.

The study was a single-site, open-label safety trial. Participants received multi-OIT with up to 5 allergens (cow's milk, egg, peanut, other nuts, grains, and sesame seeds) customized to their allergy profile. In addition, they received omalizumab injections 8 weeks before and 8 weeks after starting multi-OIT. Initial dose escalations occurred in a closely monitored hospital environment. The highest tolerated in-hospital dose determined the patients' starting daily home dose. Participants returned biweekly for dose escalation, with a goal of reaching a 4000-mg daily dose for each allergen. Escalation protocols were adapted to individual tolerances. Home reactions were recorded in symptom diaries.

The study included 25 total participants (median age, 7 years) with at least 2 food allergies documented with skin prick tests, IgE serum levels, and double-blind placebo-controlled food challenges. At initiation, 19 participants tolerated maximal dose escalation to 1250 mg per allergen. The remaining 6 patients began initial home doses at their highest tolerated doses.

Maintenance dose was reached at a median of 18 weeks, or 67 weeks earlier than participants in the earlier multi-OIT trial without omalizumab. Most (94%) reactions were mild, with only a single severe reaction requiring self-administered epinephrine.

Similar to the earlier multi-OIT without omalizumab trial, this study was also limited in its ability to demonstrate tolerance. In addition, customization of OIT regimens to each participant could have hindered comparison of specific food allergies. Finally, high total serum IgE levels are sometimes found in patients with multiple food allergies, but no participants had high total serum IgE, limiting the ability to determine optimal omalizumab dosing for such patients.

The authors mention several potential benefits of rush OIT therapy using adjunctive omalizumab. The high cost of omalizumab treatment could potentially be offset by savings incurred by fewer visits to achieve maintenance. The additional cost of school and work absenteeism during additional visits needed for multi-OIT without omalizumab is also a consideration.

"In this phase 1 safety study, we have shown that participants allergic to multiple foods were safely and rapidly desensitized to up to five food allergens simultaneously, using a rush OIT protocol with concomitant treatment with omalizumab," the authors emphasize.

The authors have disclosed no relevant financial relationships.

Allergy Asthma Clin Immunol. Published online January 15 and February 20, 2014. First study full text, Second study full text


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