Real-World Effectiveness, Corticosteroid-Sparing Effects, and Exploratory Immunological Correlates of Omalizumab...

Background/Objectives: Hospitalized patients with acute urticaria often present with rapid symptom progression, severe pruritus, angioedema, and a high risk of short-term relapse. Systemic glucocorticoids provide rapid anti-inflammatory control but raise concerns about cumulative exposure and adverse effects. This real-world study evaluates whether adding omalizumab to systemic glucocorticoids improves efficacy, safety, and steroid-sparing outcomes and explores associated immunological correlates. Methods: This retrospective cohort study evaluated the real-world, off-label use of omalizumab as add-on therapy in hospitalized patients with acute urticaria treated between 2023 and 2026. We compared UAS7 scores, itch VAS, resolution times, the primary efficacy outcome of complete remission within 7 days, the key secondary efficacy outcome of recurrence within 14 days, corticosteroid exposure, adverse events, and immune-inflammatory markers. Propensity score matching (PSM) was used to reduce imbalances in measured baseline covariates, and a multivariable exploratory model with LASSO regression identified factors linked to short-term outcomes. Results: A total of 73 patients met the eligibility criteria and were included in the study, including 39 patients who received conventional glucocorticoid-centered therapy and 34 patients who received additional omalizumab. Measured baseline characteristics were generally comparable, although imbalances remained in sex and selected leukocyte measures. The combination group showed faster UAS7 and VAS declines from Day 1, with widening differences at Days 3, 7, and 14. Combination therapy shortened the time to wheal and angioedema resolution, achieved a 7-day complete remission rate of 82.9% vs. 53.3%, and reduced 14-day recurrence to 17.1% vs. 40.0%. Total corticosteroid exposure and tapering duration were significantly reduced, with lower incidences of overall adverse events, gastrointestinal discomfort, and hyperglycemia. The exploratory model identified elevated neutrophil counts as a risk factor for poorer outcomes, while combination therapy was associated with reduced risk (bootstrap-corrected AUC 0.812, Brier score 0.126). Conclusions: In hospitalized patients with acute urticaria, adding omalizumab to systemic glucocorticoids is associated with faster symptom relief, lower short-term recurrence, reduced steroid exposure, and a better short-term safety profile. This combination may benefit selected patients with severe disease and angioedema, though prospective validation is warranted.