Omalizumab increases thresholds for reactions in multiple food allergies
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Key takeaways:
- Participants were allergic to peanut and at least two other foods.
- 67% of the treatment group could consume 600 mg of peanut.
- Patients must still practice avoidance and carry epinephrine.
WASHINGTON — Omalizumab increased thresholds for reacting to peanut and other common allergenic foods during accidental exposure, according to a study presented at the American Academy of Allergy, Asthma & Immunology Annual Meeting.
Treatment was tolerable with a safety profile similar to the placebo group, Robert A. Wood, MD, FAAAAI, professor of pediatrics, Johns Hopkins University School of Medicine, said during the presentation.
“Living with food allergy is difficult,” Wood said.
Patients with food allergy must practice constant vigilance, he continued. It also impacts nutrition, quality of life, finances and health care utilization.
“For a time, we’ve relied upon a rather simplistic approach to food allergy,” Wood said, “which is telling our patients to avoid the foods you’re allergic to, and please carry your medication with you for emergency use.”
Currently, the only FDA-approved therapy for food allergy is oral immunotherapy for peanut. Wood said that it may be the best therapy for some patients and provide some level of desensitization, but it also is burdensome and has a high rate of adverse reactions.
“If we could develop something that could address multiple food allergies simultaneously, reduce reactions upon accidental exposure and improve the overall quality of life for patients, this could be a big deal,” Wood said.
“What I really want is more options for our patients,” he said.
Study design, results
The Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen Oral Immunotherapy in Food Allergic Children and Adults (OUtMATCH) phase 3 trial included 177 children (56% boys; median age, 7 years).
“Most of the patients in my clinic don’t just have one food allergy but have multiple food allergies,” Wood said.
Each participant had a history of peanut allergy and allergy to at least two other foods from a protocol-specified list that included cashew (n = 99), milk (n = 62), egg (n = 71), walnut (n = 78), wheat (n = 20) and hazelnut (n = 24). These allergies were confirmed by skin-prick and laboratory testing as well as by oral food challenges.
The cohort had a median total IgE level of 700 IU/mL, with most participants reporting asthma, atopic dermatitis, allergic rhinitis, or all three. Also, the median maximum tolerated doses at baseline were similar for all the foods tested.
The treatment group included 118, and the placebo group included 59. Treatment varied based on weight and total IgE levels, with median doses including 300 mg (58%) every 2 weeks and 225 mg (42%) every 4 weeks.
After 16 to 20 weeks, 67% of the treatment group and 7% of the placebo group could consume 600 mg of peanut protein without dose-limiting symptoms (P < .001). Percentages of participants who could tolerate the other foods included:
- cashew: 41% of the treatment group and 3% of the placebo group (P < .001);
- Egg: 67% of the treatment group and 0% of the placebo group (P < .001);
- milk: 66% of the treatment group and 10% of the placebo group (P < .001);
- walnut: 64% of the treatment group and 13% of the placebo group;
- hazelnut: 65% of the treatment group and 14% of the placebo group; and
- wheat: 75% of the treatment group and 13% of the placebo group.
Median challenge thresholds increased from baseline through 16 to 20 weeks for all seven foods tested for all the participants in the treatment group but not for the participants in the placebo group.
Participants in the treatment group also achieved median post-treatment cumulative thresholds of at least 4,044 mg for six of the foods tested and 444 mg for cashew.
“I think that’s kind of a big deal,” Wood said. “It’s almost a whole egg. It’s 4 oz of milk. Sixteen peanuts. A whole slice of bread if you’re wheat-allergic.”
Further, the researchers noted that the treatment group had higher percentages of participants who could consume each incremental dose in the post-treatment challenges without any dose-limiting symptoms than the placebo group.
Percentages of participants who could consume any one food without adverse effects included 80% at 1,044 mg, 78% at 2,044 mg, 75% at 4,044 mg and 66% at 6,044 mg.
For any two foods, percentages fell to 69%, 66%, 54% and 42% at these dosages. They continued to fall to 47%, 37%, 31% and 24% at these dosages for any three foods.
“We have this rigid definition of success, but it doesn’t necessarily translate completely back to talking to our patients in the clinic,” Wood said. “If someone reacted to peanut or cashew with 3 mg in their baseline challenges and they can tolerate 300 mg in their post-treatment challenge, they’ve got a lot of protection. Their life is very different.”
An open-label extension with continued treatment showed that these challenge thresholds remained the same or increased through 40 to 44 weeks of treatment.
Specifically, challenge thresholds for peanut in the treatment group remained the same for 45%, increased for 34% and fell for 21%. By food, median changes spanned 0 mg to 2,000 mg, and mostly small decreases, the researchers said.
Not all patients experienced success, Wood noted.
“We had 14% who couldn’t get to 30 mg of any food,” Wood said. “As we talk to our patients about this, we need to be aware of these differences in individual patients and in differences potentially between different foods.”
The researchers also found that the caregiver and participant Food Allergy Quality of Life questionnaire scores did not change from baseline through 16 weeks, although there were changes during the open-label extension.
The treatment and placebo groups reported similar incidence and severity of adverse events including treatment-related adverse events, with injection-site reactions more common in the treatment group. Also, the open-label extension did not include any serious adverse events.
“Omalizumab is a very safe drug,” Wood said, although he noted that it carries a warning for anaphylaxis. “It is a real issue. We need to be aware of it. And it has special implications in terms of how we administer the drug.”
Patients will need to receive the first three doses in a medically supervised environment because of this risk, Wood said. After that, he said, most patients can continue with home administration.
Conclusions, next steps
Based on these findings, the researchers said that omalizumab could provide levels of protection that would be more than sufficient for protecting patients against developing reactions from the amounts of food that they typically would encounter in accidental exposures, even if they have multiple food allergies.
The researchers characterized these totals as larger than a whole nut, a bite of a baked good or a sip of milk, which would be sufficient for day-to-day protection regardless of the food allergy.
But when omalizumab is used as monotherapy, the researchers cautioned, patients would still require ongoing dosing and avoidance of the foods that they are allergic to, and they would need to continue to carry epinephrine as well.
Still, the researchers said, 16 weeks of treatment substantially increased threshold reactivity to levels that would provide protections from accidental exposure to multiple food allergens.
Wood also acknowledged that questions remain, but the researchers will investigate them in later stages of the study. For example, how can physicians predict how individual patients will respond to treatment?
“We don’t have any good predictors yet,” Wood said.
A second paper will explore predictors and correlates of response, he said, although this first study surprisingly indicated that patients with higher IgE did better with omalizumab.
“That keeps standing out in all of the different models we’re setting up with the statisticians right now,” Wood said.
The researchers also will compare dosing every 2 weeks against dosing every 4 weeks, in addition to the impact that treatment with omalizumab will have on OIT compared with omalizumab treatment alone.
“We are sorry we don’t have the answer for your patients tomorrow,” Wood said. “But we have gallons of blood in the freezer, and really, really smart collaborators are looking at this from a mechanistic standpoint and a statistical standpoint.”
Looking further ahead, the researchers will explore whether patients will be able to begin eating allergenic foods beyond accidental doses.
“The truth is, we can introduce foods,” Wood said. “There may be something beyond that will never actually achieve an FDA label but may be very important to our patients.”
Perspective
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Omalizumab works by blocking IgE antibodies and, therefore, reduces the likelihood for moderate to severe allergic reactions. It must be continued indefinitely to continue to provide protection.
Children and adults with food allergies who take omalizumab would be safer in classrooms, restaurants and many other settings where there is a risk for cross-contamination or accidental exposure.
Since omalizumab acts in a way that is not allergen-specific, patients should have the same protection with all IgE-mediated food allergies beyond those specifically included in the OUtMATCH study, such as seafood, sesame and legumes.
Although patients who are on omalizumab may be safer, it is not a cure, so they will still need to avoid their food allergens, and, importantly, they must always carry epinephrine.
Omalizumab also has significant potential to be used in conjunction with OIT to desensitize patients to their allergens. With OIT, patients eat gradually increasing amounts of their food allergen over 6 to 9 months to help build up the body’s tolerance to those foods. Patients who use omalizumab may experience fewer side effects during active OIT treatment.
Food allergy treatment is highly personalized. This is a very exciting option for families that could help them to live life more freely. I encourage patients to discuss all their treatment options with a board-certified allergist.
We are very excited that omalizumab has been formally approved as an option to help manage food allergies. Our patients, especially our teen, college-age and adult patients, are very eager to learn more about this new option.
There has been a lot of speculation in the media about the cost of the drug for this indication. It is important to note that the cost of omalizumab can vary widely depending on the patient’s insurance plan, copays and prescribed treatment plan.
Now that omalizumab has been approved for food allergies, it is likely that more insurance plans will cover some of its cost for food allergy patients. However, FDA approval for a new indication does not always equate to immediate insurance coverage. Patients should contact their insurance plan to understand their specific coverage.
As an anti-IgE monoclonal antibody that works by inhibiting the allergic reaction process, this injectable medication has been used to treat other allergic diseases such as asthma, chronic urticaria and nasal polyps for several years with a high level of safety. This FDA approval paves the way for important insurance coverage for the specific food allergy indication.
Food allergy testing also continues to be a vital part of a complete treatment plan. Patients should not be offered omalizumab without accurate testing, including skin testing, IgE blood testing and OFCs when relevant.
Omalizumab dosing for food allergies will depend on total IgE blood tests and body weight, and it is only available as an injection. The initial doses are given in a doctor’s office, and then it is continued every 2 to 4 weeks.
Also, omalizumab does not work immediately and should not be used to treat allergic reactions. It can take a few doses to provide protection, and it is not proven to provide lasting immune system change once the medication has been stopped, so the treatment does require a long-term commitment.
At Latitude Food Allergy Care, our expert providers are uniquely ready to offer this new option as part of our patients’ personalized treatment plans. We expect to offer this medication as a monotherapy and in conjunction with OIT.
We are hopeful that the second part of this pivotal study, which is expected to be published in August and will evaluate the use of omalizumab as an adjunct for OIT, will help to improve insurance coverage and expand treatment options for our patients. Additionally, we hope that future research will continue to illuminate biomarkers to help best customize treatment options for all food allergy patients.
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Wood RW, et al. Symposium 3570. Presented at: AAAAI Annual Meeting; Feb. 23-26, 2023; Washington, D.C.
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