Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- Explain that immunotherapy for kids’ milk allergy may be far more effective with oral rather than sublingual dosing.
- Note that the children’s reactions to oral dosing required treatment more often with antihistamines or with inhaled beta-agonists, but there was no difference in the rate of reactions requiring epinephrine.
- Note that any form of immunotherapy for food allergies remains investigational and may not reach routine clinical practice for years yet.
SAN FRANCISCO — Immunotherapy for kids’ milk allergy may be far more effective with oral rather than sublingual dosing — although at the cost of more severe adverse events, researchers found in the first head-to-head comparison of therapy.
Oral immunotherapy allowed 60% (nine of 15) of the children with previously severe reactions to dairy to drink a full 8 oz cup of milk without problems during treatment, but only one of the ten on sublingual immunotherapy could pass the same desensitization challenge (P<0.01).
The study by Corinne Keet, MD, of John’s Hopkins Children’s Center in Baltimore, and colleagues was reported here at the American Academy of Allergy, Asthma & Immunology meeting.
Keets’s group also reported that oral doses of powdered milk given with food didn’t cause more symptoms overall than a liquid extract held under the tongue (25% versus 29% of doses caused symptoms).
But the children’s reactions to oral dosing required treatment more often with antihistamines (11% versus 1%) or with inhaled beta-agonists (1% versus 0.1%).
The most serious reactions requiring epinephrine, though, were equally uncommon at less than 0.1% for both groups.
It came as no surprise that oral immunotherapy carried more adverse effects, noted coauthor a. Wesley Burks, MD, of Duke University Medical Center, at a press conference where the study results were discussed.
The overall evidence suggests that about 15% of children cannot tolerate oral immunotherapy right from the start, largely due to gastrointestinal side effects, Burks pointed out.
But the lack of any options to treat food allergy aside from avoidance and symptom management makes the evidence on efficacy for oral immunotherapy “exciting and encouraging, though very preliminary,” added another study coauthor Robert Wood, MD, of Johns Hopkins, who also spoke at the press conference.
Hugh a. Sampson, MD, of the Mt. Sinai School of Medicine in New York City, who was not involved in the study, agreed that oral immunotherapy looks most promising to treat kids who can’t tolerate eating raw or baked forms of a food.
“It’s nice to finally tell patients that we may be able to do something other than take things away from them,” he said at the press conference. “That’s very exciting.”
All agreed, though, that any form of immunotherapy for food allergies remains investigational and may not reach routine clinical practice for years yet.
One question is whether the desensitization shown in the studies will produce a truly permanent tolerance to the food off treatment, Burks told attendees at a separate session at the conference.
All the immunotherapy studies show that threshold for an allergic reaction rises while on treatment, albeit with large variability among individuals in the degree of improvement, he noted.
In the study Keet presented, “after 18 months of therapy with oral immunotherapy, most subjects are desensitized but not truly tolerant,” she cautioned.
The study included 30 children ages 6 to 16 who could tolerate a median of only 100 mg (less than half a teaspoon) of milk at baseline on food challenge.
The entire study group began on sublingual immunotherapy and then were randomized to either continued daily sublingual dosing, escalated to reach 7 mg (about 1/20th of a teaspoon) of a milk extract liquid held in the mouth for a few minutes before swallowing — or to switch to daily oral immunotherapy with a goal of 1,000 mg or 2,000 mg of a nonfat dry milk powder swallowed immediately.
After 15 months of maintenance therapy, eight of the nine oral immunotherapy-group kids who passed the full desensitization food challenge and stopped daily treatments remained tolerant of milk after one week off therapy, as did the one child in the sublingual group who passed the food challenge at 15 months.
After six weeks off maintenance, only five in the oral therapy group and one in the sublingual group continued to be able to drink a glass of milk without reaction (P=0.23).
This suggested most kids wouldn’t be truly tolerant after 15 months at the doses tested, Keet noted.
However, even those who failed the challenges reacted at a higher dose threshold than before, she told the audience. the lowest level tolerated at six weeks off oral immunotherapy was 2,540 mg — far above what even the most tolerant child in the study could handle at baseline.
Immunoglobulins, skin prick testing, and other mechanistic studies affirmed greater response with oral immunotherapy than with sublingual immunotherapy, although without evidence of intrinsic basophil desensitization.
Keet reemphasized, though, that despite the promising results, more study is needed to translate the results to the clinic.
Keet reported having no conflicts of interest to disclose.
Burks reported consulting for McNeil Nutritionals and Novartis; being on an advisory board or expert panel for Nutricia and Dannon co. Probiotics; being a minority stockholder in Allertein and Mast Cell; and recieving research funding from the NIH, Food Allergy Initiative, Food Allergy and Anaphylaxis Network, Food Allergy Project, and the Wallace Research Fund.
Wood reported advisory board and grant relationships with the Food Allergy and Anaphylaxis Network and the NIH.
Sampson reported being a shareholder with Herbal Springs and consultant with Genentech.