Repeated Relapse-Retreatment Cycles After Omalizumab Withdrawal in Chronic Spontaneous Urticaria: A Real-World Study.

Background/Objectives: Relapse after omalizumab withdrawal is common in chronic spontaneous urticaria (CSU), but patients requiring repeated treatment re-initiation across successive withdrawal cycles remain poorly characterized. This study aimed to characterize patients with repeated relapse requiring omalizumab re-initiation and to determine whether routinely available baseline parameters could distinguish them from other patients with CSU. Methods: This retrospective, single-center study included 46 adults with CSU who achieved disease control with standard-dose omalizumab after an initial 6-month course. Patients were evaluated during a fixed 12-month period following the first withdrawal. Repeated omalizumab re-initiation was defined as relapse requiring re-initiation within 12 weeks after withdrawal on at least two occasions. Baseline clinical and laboratory characteristics were compared between groups, and multivariable logistic regression was performed. Results: Twenty-nine patients (63.0%) met the criteria for repeated omalizumab re-initiation. Baseline disease activity, angioedema, atopic status, autoimmune thyroid disease, previous systemic corticosteroid use, total immunoglobulin E (IgE), anti-thyroid peroxidase antibody (anti-TPO), C-reactive protein (CRP), eosinophil and basophil counts, and inflammatory indices did not differ significantly between the repeated-treatment and comparison groups. Vitamin B12 was the only laboratory parameter showing a significant between-group difference in univariable analysis (259 vs. 335 pg/mL; p = 0.034); however, this association was not retained after multivariable adjustment. None of the variables included in the multivariable model were independently associated with repeated omalizumab re-initiation. Conclusions: Repeated relapse requiring omalizumab re-initiation across successive withdrawal cycles was common during the 12-month observation period. Routinely available baseline clinical and laboratory parameters did not reliably distinguish patients who developed this relapse-retreatment pattern. These findings highlight the difficulty of predicting repeated retreatment requirements from conventional baseline assessments and support further prospective investigation of individualized withdrawal and step-down strategies in patients who develop recurrent relapse-retreatment cycles.