SAN FRANCISCO – Oral immunotherapy bested sublingual immunotherapy for pediatric milk allergies in the first head-to-head comparison of the two desensitization techniques.
"The results are quite striking in that we found that both groups had significant increases in the amount of milk they could tolerate, but the oral immunotherapy group had a far greater increase," said senior investigator Dr. Robert A. Wood, professor of pediatrics and chief of the division of allergy and immunology at Johns Hopkins Children’s Center, Baltimore, Md.
However, oral therapy – in which powdered milk extract is put in food and taken as a daily treatment – had more frequent adverse events.
Twelve girls and eighteen boys aged 6-17 years participated in the trial. At baseline, they reacted to less than half a teaspoon of milk and had a median baseline milk-IgE of 37.8 kUa/L, with a range 1.1-572 kUa/L.
Ten randomized to sublingual therapy were gradually escalated to maintenance doses of 7 mg of milk extract per day placed under their tongues, held for a few minutes, then swallowed.
Ten children in the oral group were gradually escalated to daily maintenance doses of 1,000 mg, ten others to 2,000 mg.
One girl dropped out because she had a severe eczema flair, but the others reached the maintenance dose and completed milk challenges.
After 3 months of maintenance, children in the sublingual group tolerated a median of 940 mg of milk – a little less than an ounce – with a range of 40-8,140 mg.
Children in the 1,000 mg oral group tolerated a median of 6,140 mg with a range of 2,540-8,140 mg. Those in the 2,000 mg group tolerated 8,140 mg of milk with a range of 4,140-8,140 mg. The findings were statistically significant.
Six children in the sublingual group repeated the challenge at 14 months; one tolerated 8,000 mg, but the rest tolerated less than 1,000 mg and were switched to oral therapy, Dr. Wood said.
Skin prick tests decreased and milk-IgG4 increased in all the groups. Milk-IgE decreased only after oral immunotherapy. Milk-IgE or milk-IgG4 did not predict food challenge outcomes.
Dr. Wesley Burks
Side effects were similar between the sublingual and oral groups, but more severe in the oral groups. Antihistamines were needed with only about 1% of the sublingual doses, but with 18% of the oral doses. Epinephrine was used twice during sublingual therapy but four times during oral therapy.
Oral therapy’s greater side effects didn’t surprise coinvestigator Dr. Wesley Burks, chief of the division of pediatric allergy and immunology at Duke University Medical Center, Durham, N.C.
"In general, oral has more side effects." In immunotherapy trials, "about 15% of children cannot tolerate the procedure at all. They have too many [gastrointestinal] symptoms," he said.
Although promising, Dr. Wood noted the results are preliminary.
His study, as well as immunotherapy trials for peanuts and other allergens, have "very small numbers where we are trying to figure out the right doses and right way to do it. We are hopeful in the next few years we will be comfortable enough with the approach to be able to do some larger studies," he said.
Dr. Wood said he had no relevant financial disclosures. Dr. Burks disclosed that he is a consultant for Actogenix, Dannon, Intelliject, McNeil Nutritionals, Novartis, Schering-Plough (now part of Merck), and Nutricia. He is a minority stockholder in Allertein Therapeutics and Mast Cell Pharmaceuticals Inc.