Phenotype May Predict Omalizumab Response in Chronic Spontaneous Urticaria

Baseline basophil count and basophil functional phenotype, as identified by histamine release response to anti-immunoglobulin E (IgE), may predict response to omalizumab in patients with chronic spontaneous urticaria, study results in the Journal of Allergy and Clinical Immunology suggest.

The study included 18 adult patients with refractory chronic spontaneous urticaria who received 300 mg omalizumab monthly for a total of 90 days. Participants recorded their daily Urticaria Activity Scores (UAS), which was used to assess urticaria control throughout the study. Researchers also performed clinical assessments via blood sampling at baseline and on days 1, 3, 6, 10, 20, 30, 60, and 90.

The investigators evaluated in vitro histamine release responses to anti-IgE antibody to categorize patients as responders (n=7), nonresponders (n=10), or unclassified (n=1). Responders had at least a 10% release of cellular histamine content, while nonresponders had a less than 10% release. Patients were also classified as basopenic (n=9) or nonbasopenic (n=9). At baseline, the mean UAS on day 7 (UAS-7) was 29, even with the use of antihistamines.

Nonresponders had a significantly greater baseline UAS-7 (33 vs 23; P <.01). Patients who were responders and nonbasopenic had a more rapid and complete improvement in symptoms compared with nonresponders and basopenic patients. These patients also had an average earlier 50% reduction in UAS-7 (12.5 vs 20 days).

Increased anti-IgE mediated basophil histamine release was observed by day 6 across all groups, compared with baseline, but these changes were not associated with improvements in symptoms. Basophil histamine release did not change during treatment in nonresponders who were classified as basopenic.

The investigators observed similar kinetics of the reduction in surface IgE/high-affinity IgE receptor (FcεRI) across all 3 phenotypes. The kinetics were also independent of clinical response timing. In addition, plasmacytoid dendritic cells’ surface IgE/FcεRI decline as well as toll-like receptor 9-induced interferon-α responses did not mirror clinical change in patients.

Limitations of this study included its observational nature, the short follow-up period, and the small sample size.

The investigators concluded that it is unclear why the identified “phenotype is predictive because it doesn’t appear to be related to what is happening to surface IgE or FcεRI,” implying that further research is needed to determine mechanisms underlying the predictive potential.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Johal KJ, Chichester KL, Oliver ET, et al. The efficacy of omalizumab treatment in chronic spontaneous urticaria is associated with basophil phenotypes. J Allergy Clin Immunol. Published online March 10, 2021. doi:10.1016/j.jaci.2021.02.038