Is Omalizumab Monotherapy Sufficient in Chronic Spontaneous Urticaria? Clinical Predictors of Treatment Insufficiency in a Cross-Sectional Cohort

Background: Omalizumab is an established third-line therapy for chronic spontaneous urticaria (CSU); however, a substantial proportion of patients require additional treatments despite standard dosing. Identifying clinical predictors of monotherapy insufficiency remains clinically relevant for optimizing treatment strategies. Objective: This paper aims to evaluate the sufficiency of omalizumab monotherapy in CSU patients and to identify clinical and laboratory predictors associated with treatment insufficiency. Methods: This cross-sectional study included 50 CSU patients receiving omalizumab therapy. Demographic characteristics, disease duration, angioedema presence, inducible urticaria, treatment parameters, and laboratory biomarkers were analyzed. Patients were stratified according to omalizumab monotherapy response as sufficient or insufficient. Comparative analyses and logistic regression were performed to determine predictors of treatment insufficiency. Results: Monotherapy response data were available for 48 patients. Omalizumab monotherapy was sufficient in 26 patients (54.2%) and insufficient in 22 patients (45.8%). Body mass index (BMI) was significantly higher in the monotherapy-insufficient group compared with sufficient responders (median 29.05 vs 25.40 kg/m², p = 0.006). Age, sex distribution, disease duration, angioedema presence, inducible urticaria, total IgE levels, inflammatory markers, and thyroid function tests were comparable between groups. Anti-thyroid peroxidase antibody levels were higher in insufficient responders (p = 0.022); however, patient numbers were limited. Most patients received standard 300 mg/month dosing. Dose escalation to 450 - 600 mg was rare and did not result in sufficient disease control in escalated cases. Multivariate logistic regression identified higher BMI as the only independent predictor of omalizumab monotherapy insufficiency. Conclusion: Approximately half of CSU patients required additional therapy despite omalizumab treatment. Elevated BMI was independently associated with monotherapy insufficiency, suggesting a potential impact of adiposity on biologic treatment response. Dose escalation alone may not overcome treatment resistance, underscoring the need for phenotype-driven therapeutic strategies in refractory CSU.