Phenomenon of early and late response in chronic urticaria: analysis of complete symptom control durability and pathways to optimize therapy for exacerbations after omalizumab discontinuation

BACKGROUND: Chronic urticaria is a heterogeneous disease where anti-IgE therapy with omalizumab is the standard of care for antihistamine-resistant cases. However, variability in response timing and high relapse rates after drug withdrawal require objective biomarkers to optimize treatment duration and reduce pharmacological burden.

AIM: To evaluate the impact of early vs. late clinical response phenotypes on total treatment duration and post-withdrawal symptom control retention based on real-world data, and to provide a scientific rationale for omalizumab retreatment as a steroid-sparing strategy.

METHODS: A retrospective single-center study analyzed 50 patients with severe chronic urticaria across 84 omalizumab treatment episodes (300 mg every 4 weeks). Early response was defined as complete disease control (UAS7 = 0 and UCT = 16) at months 2 and 3. Relapse-free duration, systemic corticosteroid requirement, and baseline biomarkers were evaluated.

RESULTS: Early response was recorded in 32 episodes (40.5%), and late response in 47 (59.5%). Median relapse-free duration after withdrawal did not differ between early and late responders: 2.00 vs. 3.00 months (p = 0.256). However, early responders required significantly fewer injections: 8.00 vs. 12.00 (p < 0.001). Post-withdrawal exacerbations were severe in 70.0% of cases. Early response associated with higher baseline total IgE (226.00 vs. 89.20 IU/mL; p = 0.011) and lymphocyte counts (2.67 × 10⁹/L vs. 2.04 × 10⁹/L; p = 0.019). Long-term drug-free remission (>12 months) occurred in 34.5% of patients (n = 29) and correlated with lower baseline total IgE (55.50 vs. 150.00 IU/mL; p = 0.049), higher Systemic Immune-inflammation Index (637.40 vs. 466.08; p = 0.031), and higher platelet-to-lymphocyte ratios (131.07 vs. 120.66; p = 0.031). Logistic regression models were developed to estimate early response and long-term remission probabilities.

CONCLUSION: The speed of achieving symptom control during omalizumab therapy does not affect relapse-free duration after drug withdrawal. The identified biomarker inversion phenomenon supports a personalized approach: short intermittent steroid-sparing courses for early responders and extended therapy for patients with an autoimmune endotype.