Omalizumab may help treat idiopathic anaphylaxis in patients who failed on prior therapies

Omalizumab may effectively treat idiopathic anaphylaxis in patients without indication of mast cell clonality and who have failed on prior treatments, according to study results published in Annals of Allergy, Asthma & Immunology.

“Anaphylaxis, a potentially life-threatening systemic reaction, is most commonly caused by stinging insects and medications in adults and by foods in children and adolescents. However, in about 13% to 18% of patients, no triggers are identified, and these patients are diagnosed with idiopathic anaphylaxis, [which] can be a manifestation of clonal mast cell disorders such as systemic mastocytosis and monoclonal mast cell activation syndrome; however, evidence of mast cell clonality is absent in most of these patients,” Lauren W. Kaminsky, MD, PhD, researcher in the section of allergy, asthma and immunology in the department of medicine at Penn State College of Medicine, and colleagues wrote.

According to the researchers, patients with idiopathic anaphylaxis may not respond to a combination of high-dose H1- and H2-antihistmaines and mast cell stabilizers, making treatment options limited.

Investigators sought to assess the efficacy of omalizumab (Xolair; Genentech, Novartis) — a humanized monoclonal IgG antibody against IgE — among 35 patients (median age, 36 years; age range, 11-54 years; 70% female) with idiopathic anaphylaxis who received treatment with omalizumab and had no evidence of mast cell clonality. Fourteen of these patients were treated at either Penn State Health or University of Washington/Northwest Asthma & Allergy Center and were identified in a chart review, and 21 were identified from a systematic literature review.

Researchers gathered data on symptoms and treatment and determined response pattern of anaphylaxis. Response pattern to omalizumab defined as complete, partial or no response served as the primary outcome. Secondary outcome was major adverse events to omalizumab.

Median duration of follow-up was 1 year (n = 29).

Results showed the number of idiopathic anaphylaxis episodes before treatment with omalizumab varied from two episodes to several episodes per month. Symptoms of idiopathic anaphylaxis evaluated among patients in the chart review included angioedema in 79% (n = 11), urticaria in 93% (n = 13), flushing in 36% (n = 5), dyspnea or wheezing in 71% (n = 10), gastrointestinal manifestations in 50% (n = 7), pre-syncope or syncope in 50% (n = 7) and hypotension in 43% (n = 6). In addition, 64% of patients (n = 9) had allergic rhinitis, 43% (n = 6) had asthma, 14% (n = 2) had atopic dermatitis and 29% (n = 4) had IgE-mediated food allergy.

Most (63%) patients achieved a complete clinical response to omalizumab, 28.5% had a partial response and three patients (8.5%) did not respond to treatment.

Sixteen patients received an initial dose of 300 mg omalizumab every 4 weeks. Of those 16 patients, 75% achieved a complete clinical response, 19% had a partial response and one patient did not respond to treatment.

Limitations of the study included the small sample size and the inclusion of patients with a physician diagnosis of idiopathic anaphylaxis, with most patients lacking confirmatory studies such as a rise in event-related tryptase level.

“Larger studies are needed to be able to make management recommendations for use of omalizumab for idiopathic anaphylaxis. Additional considerations include extended duration at follow-up after omalizumab start as there may be a delay in onset of action and possibility of dose and/or frequency increases if no response or only partial response to omalizumab is initially achieved,” Kaminsky and colleagues wrote. “The current study provides preliminary results that may serve to inform physicians caring for patients with idiopathic anaphylaxis, especially those unresponsive to high-dose nonsedating antihistamines and those who are steroid-dependent.”