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Background In our recent clinical trial, the addition of omalizumab to oral immunotherapy (OIT) for milk allergy improved safety, but no significant clinical benefit was detected. Objective We sought to investigate mechanisms by which omalizumab modulates immunity in the context of OIT and to identify baseline biomarkers that predict subgroups of patients most likely to benefit from omalizumab. Methods Blood was obtained at baseline and multiple time points during a placebo-controlled trial of OIT for milk allergy in which subjects were randomized to receive omalizumab or placebo. Immunologic outcomes included measurement of basophil CD63 expression and histamine release and casein-specific CD4 + regulatory T-cell proliferation. Biomarkers were analyzed in relationship to measurements of safety and efficacy. Results Milk-induced basophil CD63 expression was transiently reduced in whole blood samples from both omalizumab- and placebo-treated subjects. However, IgE-dependent histamine release increased in washed cell preparations from omalizumab- but not placebo-treated subjects. No increase in regulatory T-cell frequency was evident in either group. Subjects with lower rates of adverse reactions, regardless of arm, experienced better clinical outcomes. Pre-OIT basophil reactivity positively associated with occurrence of symptoms during OIT, whereas the baseline milk IgE/total IgE ratio correlated with the likelihood of achieving sustained unresponsiveness. A combination of baseline basophil and serologic biomarkers defined a subset of patients in which adjunctive therapy with omalizumab was associated with attainment of sustained unresponsiveness and a reduction in adverse reactions. Conclusions Combining omalizumab therapy with milk OIT led to distinct alterations in basophil reactivity but not T-cell responses. Baseline biomarkers can identify subjects most likely to benefit from adjunctive therapy with omalizumab.

Background Although studies of oral immunotherapy (OIT) for food allergy have shown promise, treatment is frequently complicated by adverse reactions and, even when successful, has limited long-term efficacy because benefits usually diminish when treatment is discontinued. Objective We sought to examine whether the addition of omalizumab to milk OIT reduces treatment-related reactions, improves outcomes, or both. Methods This was a double-blind, placebo-controlled trial with subjects randomized to omalizumab or placebo. Open-label milk OIT was initiated after 4 months of omalizumab/placebo with escalation to maintenance over 22 to 40 weeks, followed by daily maintenance dosing through month 28. At month 28, omalizumab was discontinued, and subjects passing an oral food challenge (OFC) continued OIT for 8 weeks, after which OIT was discontinued with rechallenge at month 32 to assess sustained unresponsiveness (SU). Results Fifty-seven subjects (7-32 years) were randomized, with no significant baseline differences in age, milk-specific IgE levels, skin test results, or OFC results. At month 28, 24 (88.9%) omalizumab-treated subjects and 20 (71.4%) placebo-treated subjects passed the 10-g "desensitization" OFC ( P = .18). At month 32, SU was demonstrated in 48.1% in the omalizumab group and 35.7% in the placebo group ( P = .42). Adverse reactions were markedly reduced during OIT escalation in omalizumab-treated subjects for percentages of doses per subject provoking symptoms (2.1% vs 16.1%, P = .0005), dose-related reactions requiring treatment (0.0% vs 3.8%, P = .0008), and doses required to achieve maintenance (198 vs 225, P = .008). Conclusions In this first randomized, double-blind, placebo-controlled trial of omalizumab in combination with food OIT, we found significant improvements in measurements of safety but not in outcomes of efficacy (desensitization and SU).

Rationale Underutilization of EpiPen® in food-allergic children experiencing anaphylaxis may be attributed to parental discomfort with administration, as measured by lack of parental self-perceived competence and knowledge of proper administration. Methods A written survey was mailed to parents of 360 children ( Results We received 165 completed surveys (46%) with signed consent forms. Anaphylaxis was reported in 42.4% of children (n=70); 8.5% of parents (n=14) had administered EpiPen® to their child. Factors correlating with COMFORT included prior administration of EpiPen® (p=0.009), prior training of EpiPen® use (p=0.006), and COMPETENCE (p Conclusions COMPETENCE directly correlated with increased COMFORT with EpiPen® use, but KNOWLEDGE did not. Physicians should continue to instruct all parents on EpiPen® administration, specifically with a trainer, since this correlated significantly with COMFORT. Other psychological factors, beyond those examined here, may contribute to underutilization of EpiPen®. Future studies should explore these factors.