SAN FRANCISCO - Off-label pretreatment with the biologic drug omalizumab enabled relatively rapid oral desensitization to milk allergy in a pilot study of 11 children.
One patient who dropped out of the study after 1 day of desensitization was later diagnosed as having abdominal migraines. Among the remaining 10 patients, 9 tolerated desensitization to a dose of 2,000 mg/day of powdered milk within 7-10 weeks. These nine children then passed a double-blind, placebo-controlled food challenge at weeks 24-27 and have since been consuming 8-12 ounces of milk in their daily diets at home, Dr. Kari C. Nadeau said at the meeting.
Responses to desensitization were seen within 7-11 weeks, compared with 15-16 weeks in previous studies of protocols for oral desensitization to food allergy, reported Dr. Nadeau of Stanford (Calif.) University, and her associates.
The study recruited patients at Stanford and at Children's Hospital, Boston, who had a history of acute reactions to cooked and uncooked milk, mean wheal sizes of 22 mm after skin testing, mean milk-specific IgE measurements of 98 kU/L, and mean total IgE measurements of 701 kU/L. Patients averaged 10 years in age.
For 9 weeks they took omalizumab (Xolair), an anti-IgE monoclonal antibody drug that is approved to treat patients 12 years or older with moderate-to-severe persistent allergic asthma that is insufficiently controlled by inhaled corticosteroids.
Then, in 1 day they underwent a "rush" desensitization to oral doses of 1,000 mg of milk powder, to a cumulative dose of 2,000 mg. Seven patients passed the 1-day desensitization.
From weeks 9 to 16, they continued on omalizumab and the dose of powdered milk was increased weekly under supervision in the medical centers.
Patients stopped taking omalizumab at week 16 but continued taking a maintenance dose of 2,000 mg/day of powdered milk at home, with regular clinic visits for assessments.
Nine of the remaining 10 patients reached an oral daily dose of 2,000 mg of powdered milk (the primary end point) by week 20, and the 10th patient tolerated a dose of 1,200 mg/day.
Nine patients passed a double-blind, placebo-controlled food challenge to up to 3,000 mg of milk and a cumulative dose of 7,200 mg at weeks 24-27. The day after passing the double-blind food challenge, the nine patients began tolerating 8-12 ounces of milk per day in their diet, including ice cream, pizza, and yogurt, Dr. Nadeau said.
Dr. Dale T. Umetsu of Harvard Medical School, Boston, who was the principal investigator in the study, said in an interview that the combination of omalizumab and oral desensitization "allowed us to move relatively quickly in increasing the dose of milk from a very small dose to a very large maintenance dose of milk."
At some point during the study, each of the 11 patients developed a reaction to the milk, and most had 10-11 reactions over the course of the study. Patients have been followed for up to 52 weeks.
The children received a mean of 209 milk doses each. Among the 2,301 total doses, 41 (2%) generated reactions, most of which were mild. Epinephrine was administered for three of the reactions. Most reactions consisted of pruritus, urticaria, or abdominal pain, all of which were treatable, Dr. Nadeau said.
Among 29 reactions with mild symptoms, 14 occurred on the rush-desensitization day, 10 occurred during the weekly dose-escalation phase, and 5 happened during the maintenance phase.
Among eight reactions with moderate symptoms, five occurred on the rush desensitization day, one occurred during the weekly dose-escalation phase, and two occurred during the maintenance phase.
The four reactions with severe symptoms included one patient with tongue swelling and another with disseminated urticaria on the rush-desensitization day, one patient with severe abdominal pain during the weekly dose-escalation phase, and one patient with vomiting during the maintenance phase.
The results of this pilot study need to be confirmed in larger, placebo-controlled, phase II trials that also should identify the optimal dose of omalizumab and subsets of patients with food allergies who might be most likely to benefit from this approach, Dr. Nadeau said. "I don't think this is ready for prime time," she said. "This is a wonderful potential cure for food allergies, but it takes a lot of potential work to get there."
There are no approved treatments for food allergy other than avoiding the offending foods and keeping self-injectable epinephrine handy to treat reactions.
This study appears to be the first to combine omalizumab with oral desensitization for food allergy. Previous studies of oral desensitization regimens have reported success rates of 37%-47%, she said.