Omalizumab may be associated with a higher rate of treatment success compared with omalizumab-facilitated multiallergen oral immunotherapy among patients with multifood allergy in an intention-to-treat analysis of a randomized clinical trial.
Investigators conducted stage 2 of the multicenter, double-blind, placebo-controlled OUTMATCH trial at 10 US academic centers. Patients aged 1 to 55 years were eligible if they had a peanut allergy and allergy to at least 2 additional study foods: milk, eggs, wheat, cashews, hazelnuts, or walnuts. Eligibility required dose-limiting symptoms during oral food challenges at a single dose of 100 mg or less of peanut protein or 300 mg or less of each nonpeanut allergen, corresponding to cumulative doses of 144 mg and 444 mg, respectively. The patients were excluded if they exhibited poorly controlled or severe asthma, history of life-threatening anaphylaxis to participant-specific foods, history of eosinophilic gastrointestinal disease, or recent food or other immunomodulatory therapy.
A total of 117 participants were randomly assigned to omalizumab-facilitated multiallergen oral immunotherapy (MOIT) or omalizumab with placebo MOIT. They underwent 16 weeks of open-label treatment with omalizumab; active or placebo MOIT began at week 8. The participants then received blinded omalizumab or placebo injections for another 44 weeks. Active MOIT was escalated toward a maximum maintenance dose of 1,000 mg per food.
The primary endpoint was a cumulative-tolerated dose of at least 4,044 mg for each of 3 foods without dose-limiting symptoms. The participants who withdrew prior to the final food challenges were classified as treatment failures. In the intention-to-treat analysis, 36% of participants receiving omalizumab met the primary endpoint vs. 19% receiving MOIT. The per-protocol analysis among participants who completed stage 2 did not show a statistically significant difference between groups.
Overall, 88% of the participants receiving omalizumab completed the study vs. 51% receiving MOIT. Most discontinuations in the MOIT group were associated with adverse events, serious adverse events, or MOIT-associated symptoms.
In a post hoc analysis, 72% of the participants receiving omalizumab vs. 39% receiving MOIT tolerated at least 444 mg of all 3 allergens. At the predefined secondary 8,044-mg threshold, 24% vs. 10% tolerated all 3 foods, respectively. The corresponding per-protocol analyses did not show statistically significant differences between groups.
Serious adverse events occurred in 31% of those receiving MOIT vs. 0% receiving omalizumab. Overall, adverse events treated with epinephrine occurred in 37% vs. 7%, respectively, and adverse events leading to treatment discontinuation occurred in 22% vs. 0%. Three cases of biopsy-confirmed eosinophilic esophagitis occurred in the active MOIT group. Under the study protocol, epinephrine administered for reactions related to MOIT or placebo MOIT dosing, omalizumab or placebo injections, or unintentional allergen exposures was classified as a serious adverse event; epinephrine administered during oral food challenges was not.
The investigators noted several limitations, including a smaller-than-planned sample after stage 1 enrollment ended early following evidence of omalizumab efficacy and subsequent US Food and Drug Administration approval. They also noted that their selection of the primary endpoint may have been overly optimistic. Most of the additional endpoints favored omalizumab and none favored MOIT, including in the per-protocol population. The investigators noted that participants with multifood allergies and low baseline cumulative tolerated doses may not be representative of the broader population with food allergy.
“Both omalizumab and omalizumab-facilitated MOIT represent viable treatment options, each with distinct risk-benefit profiles that must be weighed in the context of individual patient needs and preferences,” wrote lead study author Robert A. Wood, MD, of the Department of Pediatrics at Johns Hopkins University School of Medicine, and colleagues.
The study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Advancing Translational Sciences, Genentech, and Novartis. Full disclosures of the study authors can be found in the study.
Source: JAMA Pediatrics
