Until last month, treatment of food allergy outside of academic medical centers was either avoidance or an attempt to desensitize by oral immunotherapy–known by the shorter acronym OIT. Research and increasing use of sublingual (i.e. under the tongue) desensitization–known as SLIT–by some community-based allergists has also gained momentum over the past several years. However, treatment options changed rather dramatically on February 16th, when the FDA approved Xolair, a genetically engineered monoclonal antibody available since 2003, to be used to reduce allergic reactions, including prevention of anaphylactic reactions, from accidental ingestion of small amounts of one food or of multiple foods to which a person is allergic.
To summarize the data from the clinical trial (called OUtMATCH) that compared Xolair with placebo in 177 food allergic children and adolescents:
Effectiveness:
- The headline result is that 67% of those who receive Xolair were able to tolerate at least a single dose of peanut equivalent to ~2 kernels of peanut and a cumulative dose of ~ 4 peanut kernels.
- For other foods, in which 1000 mg were ingested by Xolair-treated patients and the results were also statistically significant from placebo-treated groups:(1) 67% were able to tolerate 2% of the weight of an average-sized egg.(2) 66% were able to tolerate approximately 4 teaspoons of cow’s milk.(3) 41% were able to tolerate approximately 3 cashews.
- Similar results, from 65% to 75%, were seen for walnut, hazelnut and wheat. But these foods did not meet the statistically significant differences from placebo-treated individuals because these foods were not part of the interim analysis for multiple testing.
Safety:
- Other than injection site reactions that were more common in the Xolair-treated group, adverse events were comparable to the placebo-treated group.
- A 1 year-old child who received Xolair had liver enzyme elevations and was withdrawn from the study; however, a complete evaluation determined that Xolair was unlikely to be the cause.
Cautionary Findings:
- Decreasing percentages of food tolerance occurred with higher amounts of food and with additional foods to which a person was allergic. For example, 80% could eat 1044 mg of one food, 69% could tolerate a total of 1044 mg of two foods and 47% could tolerate a total of 1044 mg of three foods.
- When the treatment time was extended from 16-20 weeks to 40-44 weeks, the peanut dose threshold for most Xolair-treated people either remained the same or improved. But, 21% developed a lower threshold for reacting to peanut, which raises a question about how long the Xolair effect lasts with continued use.
- Since the definition of a responder was based on tolerating a specific amount of the food, some patients were left out of being considered responders even though they could tolerate a greater amount of food while on Xolair.
- While there were only three adults in the clinical trial, the FDA agreed to include adults in its approval of Xolair to treat food allergy because the FDA acknowledged the immune system response to a food allergen to be the same regardless of age.
For those who have had moderate to severe allergic reactions to one food or to multiple foods, Xolair is completely reasonable to use to protect from having another reaction. Avoidance, though, must still be practiced. Clinicians have been waiting for over 20 years for Xolair to be approved by the FDA, and for subsequent coverage by insurers, since the proof-of-concept study was published in the New England Journal of Medicine in 2003 and demonstrated effectiveness with a virtually identical monoclonal antibody. When the lead researcher presented the Xolair clinical trial results eight days ago as a late-breaking symposium to a standing-room-only audience at the American Academy of Allergy, Asthma and Immunology annual meeting, more than just a few in the audience stood to applaud afterward. The professional relief now felt in our specialty from not having to only offer the uncertainties of avoidance and the risks of allergic reactions during OIT/SLIT approaches the comforting effect that parents and patients have from Xolair being available.
Parents and patients will need to decide on whether treatment should include (a) an injection every two to four weeks of Xolair at home (after the first three treatments are in a physician’s office because of a 0.2% incidence of anaphylaxis from Xolair), or (b) OIT/SLIT that would entail several months of building up to a tolerated amount that must be ingested most days per week and that has certain restrictions on daily activities to prevent allergic reactions. Xolair treatment only offers protection from unintentional ingestion of small amounts of a food allergen. Xolair treatment, as studied, does not mean that the person can eat as much as one wants; only OIT offers that possibility.
Additionally, one-third of patients overall were not considered to be responders to Xolair according to the prespecified definition of a successful response. The responder percentage was worse than one-third with cashew. Another consideration for parents and patients is that the results in the OUtMATCH trial only established safety with ingesting small amounts of cow’s milk and egg, and these two foods are especially desired to be part of one’s diet. Desensitization and dietary advancement therapy (often referred to as the ‘ladder method’) will still be considerations for those who do not ‘outgrow’ these two food allergies by age 5 or 6.
The use of Xolair for treating food allergy is more than a mere game changer (a compound word that always seemed to me to be a bit trite and overused since its use began in the 1990s). To use the vocabulary of tennis, Xolair’s FDA approval for food allergy would be a set changer. We will find out sometime in late 2024 or in 2025 how the match is decided when stage 2 results of the OUtMATCH trial are known from comparing those who stayed on Xolair with those who were switched to OIT.
Dr. Klein