Predicting Responses to Omalizumab in Antihistamine-Refractory Chronic Urticaria: A Real-world Longitudinal Study

Background Treating chronic urticaria (CU) unresponsive to H1-antihistamines (H1AHs) is challenging, and the real-world effectiveness of omalizumab remains unclear. Objective To evaluate the real-world effectiveness of omalizumab, optimal response assessment timing, and predictive factors. Methods Initially, 5,535 CU patients on ≥ 20 mg loratadine daily for ≥ 6 months (Jan 2007-Aug 2021) were screened; 386 patients receiving ≥ 6 months of omalizumab add-on treatment and were assessed for > 2 years. Predictors of treatment responses to omalizumab add-on therapy for anti-histamine refractory CU patients were identified using a generalized linear model. Results In our retrospective cohort, omalizumab treatment showed cumulative response rates of 55.2% at 3 months, 71.0% at 6 months, and 81.4% at 9 months for H1AH-refractory CU patients. Longitudinal responses to omalizumab treatment revealed three distinct clusters: favorable (cluster 1, n=158), intermediate (cluster 2, n=143), and poor responses (cluster 3, n= 85). Subjects were categorized based on achieving a complete response within 3 months, identifying 213 early responders, 117 late responders, and 56 nonresponders. The initial dose of omalizumab differed significantly among the three clusters. Low total IgE (<40 kU/L) predicted non-response (OR=3.10, P=0.018). Early responders were associated with a higher initial omalizumab dose (≥300 mg, OR=2.07, P=0.016), higher basophil counts (OR=2.0, P=0.014), total IgE levels exceeding 798 kU/L (OR=0.37, P=0.047), and lower platelet-to-lymphocyte ratio (OR=0.50, P=0.050). Conclusion Real-world data reveal three distinct clusters for omalizumab treatment responses, confirm low serum total IgE (<40 kU/L) as a predictor of nonresponse, and identify potential biomarkers, including IgE, basophils, and PLR for early responders.