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.

FIG 1

Study timeline. Key features and overall timeframe are shown. OFC, Oral food challenge.

FIG 2

Change in milk dose threshold. A, Threshold change in active group (P = .002). B, Threshold change in placebo group (P = .16). Change in threshold after open-label active treatment in the placebo group is also shown in Fig 2, B (from after placebo to after milk OIT). Change in threshold for active versus placebo groups, P = .0003. Orange bars represent medians. MOIT, Milk OIT.

FIG 3

Change in end-point titration skin prick testing. A, Threshold change in active group (P = .03). B, Threshold change in placebo group (P = .03). Change in threshold for active versus placebo groups, P = .54. Orange bars represent medians. MOIT, Milk OIT.

FIG 4

Change in milk-specific IgE levels. Results are shown before milk OIT (MOIT), at maintenance, and after MOIT for the active group (P = .75; A) and placebo group (P = .46; B). Change in threshold for active versus placebo groups, P = .87. Orange bars represent medians.

FIG 5

Change in milk-specific IgG4 levels. Results are shown before milk OIT (MOIT), at maintenance, and after MOIT for the active group (P = .002; A) and placebo group (P = .6; B). Change in threshold for active versus placebo groups, P = .001. Orange bars represent medians.