Omalizumab markedly alters the risk/benefit ratio for milk oral immunotherapy

Published Online: November 12, 2015

Cow’s milk allergy (CMA) is the most common food allergy in young children, with an estimated prevalence of 2-3%. While the mainstay of treatment remains avoidance, which is difficult given the ubiquitous nature of milk, oral immunotherapy (OIT) is under investigation for the treatment of various food allergies, with overall encouraging results. Although studies of oral immunotherapy (OIT) for food allergy have shown promise, treatment is frequently complicated by adverse reactions forcing 10-20% patients to discontinue therapy due to adverse reactions, and even when successful, has limited long-term efficacy as benefits usually diminish when treatment is discontinued. In this study, we examined whether the addition of omalizumab to milk OIT (MOIT) could reduce treatment-related reactions and/or improve the degree of protection.

In an article recently published in The Journal of Allergy and Clinical Immunology (JACI), Sampson and colleagues describe their recently completed double-blind placebo-controlled trial of milk oral immunotherapy (MOIT) in milk-allergic subjects randomized to receive omalizumab or placebo in addition to MOIT.  MOIT was initiated after 4 months of omalizumab/placebo with escalation to maintenance over a 22 - 40 week period, followed by daily maintenance dosing through month-28. At month-28, omalizumab was discontinued and subjects were challenged with milk to determine if they were desensitized. Those tolerating 10 gm of milk protein in the oral food challenge (OFC) continued OIT for another 8 weeks, after which OIT was discontinued and the patients were re-challenged at month-32 to determine whether they had achieved more long-term protection, i.e. sustained unresponsiveness (SU).

Overall 57 milk-allergic patients (7 – 32 years) were enrolled and randomized to receive either omalizumab or placebo, with no significant baseline differences in their age, milk-specific IgE, skin test results, or threshold dose for allergic reactivity in the OFC.  There was no significant difference in the number of omalizumab-treated subjects or placebo-treated subjects passing the 10g “desensitization” OFC at 28 months (p=0.11).  In addition there was no significant difference in SU between the groups at month-32; SU was demonstrated in 48.1% in the omalizumab group and 35.7% in the placebo group (p=0.42).  However, adverse reactions were markedly reduced during OIT escalation in omalizumab subjects for the percent of doses per subject provoking adverse symptoms (2.1% versus 16.1%; p=0.0005), dose-related reactions requiring treatment (0.0% versus 3.8%, p=0.0008), and doses required to achieve maintenance (198 versus 225; p=0.008).

In this first randomized double-blind placebo-controlled trial of omalizumab in combination with food OIT, omalizumab was found to provide marked, significant improvements in measurements of safety, but not in outcomes of efficacy (desensitization and SU). Most subjects could be desensitized to a high dose (10g) of milk protein over the 24 month period, but about half lost this protection following an 8 week period of avoidance. While the prospects for the treatment of food allergy are on the horizon, more research is needed to develop strategies to maintain sustained unresponsiveness.  

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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