Omalizumab for the Treatment of Multiple Food Allergies

Abstract

Background: Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy.

Methods: In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose-limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension.

Results: Of the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 67% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group.

Conclusions: In persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT03881696.).

Figure 1.. Successful Consumption of Prespecified Threshold Dose at Week 16.

Shown are the percentages of participants in the two groups who consumed the prespecified threshold doses without dose‑limiting symptoms during food challenges at the end of the first stage of the trial; these food challenges were started at week 16 and were conducted during separate visits spanning up to a 4‑week period. The prespecified threshold dose of peanut protein was a single dose of at least 600 mg; for cashew, egg, milk, walnut, hazelnut, and wheat protein, the prespecified threshold was a single dose of at least 1000 mg. The 95% confidence intervals for the differences were calculated with the use of exact unconditional confidence limits. The P values for the primary and key secondary end points are unadjusted, two‑sided values derived from Fisher’s exact test.

Figure 2.. Successful Consumption of Prespecified Secondary End-Point Doses at Week 16.

Shown are the percentages of participants in the two groups who consumed the prespecified threshold doses and the cumulative doses without dose‑limiting symptoms. The 95% confidence intervals for each group were calculated with the use of exact confidence limits, which are based on a score statistic. The food challenges at the end of the first stage of the trial were started at week 16 and were conducted during separate visits spanning up to a 4‑week period.

Figure 3.. Successful Consumption of Multiple Foods at Prespecified Secondary End-Point Doses at Week 16.

Shown are the percentages of participants who consumed prespecified doses and cumulative doses of at least two foods and of all three foods without dose-limiting symptoms. The 95% confidence intervals for each group were calculated with the use of exact confidence limits, which are based on a score statistic. The food challenges at the end of the first stage of the trial were started at week 16 and were conducted during separate visits spanning up to a 4-week period.