Spectrum and Impact of Reported Side Effects of Omalizumab in Patients With Chronic Urticaria: A Long-Term Multicentre Real-World Study

Abstract

Background: Chronic urticaria (CU) treatment with omalizumab is considered safe in short-term studies. Large real-world studies focusing on the long-term safety of omalizumab and associated factors are lacking. We aimed to investigate the spectrum of reported side effects in omalizumab-treated CU patients in a large long-term daily practice cohort. Methods: A multinational multicentre retrospective study was conducted at 14 specialised urticaria centres (UCAREs), including all CU patients ever treated with omalizumab until centre-specific data lock. The prevalence of patient-reported side effects was assessed. Results: A total of 1859 patients were included, of which 32.9% (n = 612) reported side effects during omalizumab treatment with a wide range across centres (0%–75.5%). Fatigue (15.8%, n = 293), headache (11.6%, n = 215) and flu-like symptoms (9.3%, n = 172) were most common. No events suggestive of anaphylaxis and no new notably prevalent side effects were reported. Hair loss was reported by 2.9% (n = 53/1859) of patients, leading to treatment adjustment in 21.1% (n = 8/38 with sufficient data). Patients who reported side effects were more often female (78.3% vs. 68.6%, p < 0.001), had worse disease control prior to omalizumab (Urticaria Control Test, UCT, 4.0 vs. 6.0, p < 0.001), and lower fast response (Weekly Urticaria Activity Score, UAS7, < 7 or UCT > 11 within 4 weeks, 42.6% vs. 59.5%, p < 0.001) and complete/good response rates (UAS7 < 7 or UCT > 11 at end of treatment, 72.3% vs. 84.4%, p < 0.001) compared to patients without side effects. While only 2.4% (n = 44/1859) of patients discontinued treatment due to side effects, 5.5% (n = 100/1859) and 12.8% (n = 238/1859) of patients reporting side effects with insufficient (UAS7 ≥ 7 or UCT 3–11 at end of treatment) and complete/good response, respectively, remained on omalizumab. Conclusions: The safety and tolerability of omalizumab was confirmed. Notably, the wide variation in reported side effects across centres suggests that differences in awareness influence reporting. Hair loss was more prevalent than described before, warranting extra attention. Side effects were more often reported in patients whose characteristics suggest reduced effectiveness of omalizumab, possibly related to a negative association with omalizumab and suggesting increased disease burden. Availability of new therapies might increase the impact of side effects on treatment decisions, not only in omalizumab-refractory patients but potentially even among good responders. © 2025 Elsevier B.V., All rights reserved.