A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy

Abstract

Background Orally administered, food-specific immunotherapy appears effective in desensitizing and potentially permanently tolerizing allergic individuals. Objective We sought to determine whether milk oral immunotherapy (OIT) is safe and efficacious in desensitizing children with cow’s milk allergy. Methods Twenty children were randomized to milk or placebo OIT (2:1 ratio). Dosing included 3 phases: the build-up day (initial dose, 0.4 mg of milk protein; final dose, 50 mg), daily doses with 8 weekly in-office dose increases to a maximum of 500 mg, and continued daily maintenance doses for 3 to 4 months. Double-blind, placebo-controlled food challenges; end-point titration skin prick tests; and milk protein serologic studies were performed before and after OIT. Results Nineteen patients, 6 to 17 years of age, completed treatment: 12 in the active group and 7 in the placebo group. One dropped out because of persistent eczema during dose escalation. Baseline median milk IgE levels in the active (n = 13) versus placebo (n = 7) groups were 34.8 kUa/L (range, 4.86–314 kUa/L) versus 14.6 kUa/L (range, 0.93–133.4 kUa/L). The median milk threshold dose in both groups was 40 mg at the baseline challenge. After OIT, the median cumulative dose inducing a reaction in the active treatment group was 5140 mg (range 2540-8140 mg), whereas all patients in the placebo group reacted at 40 mg (P = .0003). Among 2437 active OIT doses versus 1193 placebo doses, there were 1107 (45.4%) versus 134 (11.2%) total reactions, with local symptoms being most common. Milk-specific IgE levels did not change significantly in either group. Milk IgG levels increased significantly in the active treatment group, with a predominant milk IgG4 level increase. Conclusions Milk OIT appears to be efficacious in the treatment of cow’s milk allergy. The side-effect profile appears acceptable but requires further study.

Previously undescribed grass pollen antigens are the major inducers of T helper 2 cytokine-producing T cells in allergic individuals

“…Secondly, induction of PUTGAspecific Tregs or Th1 cells may help in the regulation, through bystander mechanisms (26), of Th2 responses directed against known TG allergens present in the same pollen particle. Thirdly, the regulation of PUTGA-specific Th2 responses may also result in downstream regulation of IgE and induction of blocking IgG antibody responses to known TG allergens, a hallmark of specific immunotherapy (SIT) treatment (27,28). Finally, induction of PUTGA-specific Th1 or Treg cells may lead to PUTGA-specific IgG production, which may interfere with IgE-induced mediator release and other immediate-type reactions by mechanisms such as steric hindrance, competition for antigen binding, and inhibitory signaling through FcγRIIB (29,30).…”

Food Allergy and the Oral Immunotherapy Approach

“…Similarly, in food allergies treated with OIT protocols for milk, egg, and peanut, decreases in the serum levels of sIgE, SPTs, BATs and increase of allergen-specific IgG4 after 3-6 months of treatment have been reported (Table 2). However, in two OIT protocols for milk allergy no differences were observed in the serum levels of sIgE (Pajno et al 2010;Skripak et al 2008) (Table 2). Specifically, in the study of Skripak et al (2008) twenty children were studied in a double blind and placebo assay, with a success rate of 92 % upon OIT to milk in the active group (13 patients).…”

“…However, in two OIT protocols for milk allergy no differences were observed in the serum levels of sIgE (Pajno et al 2010;Skripak et al 2008) (Table 2). Specifically, in the study of Skripak et al (2008) twenty children were studied in a double blind and placebo assay, with a success rate of 92 % upon OIT to milk in the active group (13 patients). Equally, Pajno et al (2010) carried out a double blind and placebocontrolled trial for OIT to milk, in 30 children obtained a 76 % of tolerance upon OFC in the active group (15 patients).…”

Oral immunotherapy for the treatment of food allergy

“…9,11,22,23,31,[36][37][38][39] This is probably due to differences in escalation protocols, allergens, selection of participants and use of prophylactic medication. Most reported symptoms tend to be local pruritus or abdominal pain which are mostly mild and can generally be controlled with anti-histamine prophylaxis or anti-leukotriene medication.…”