The recommended dose of omalizumab for the treatment of chronic spontaneous urticaria (CSU) is 300 mg every 4 weeks, but there is no recommendation for patients who do not benefit from this dose. Our aim is to present the experiences on the use of doses of omalizumab higher than those recommended for CSU patients and to propose a protocol for updosing. This was a retrospective analysis of patients treated with omalizumab for CSU from 2 urticaria centers in Istanbul and Barcelona. The weekly urticaria activity score and/or the Urticaria Control Test (UCT) were used to monitor response. In Barcelona, a stepwise updosing regimen was preferred (450 mg first, then increasing to 600 mg), while in Istanbul, direct updosing to 600 mg was chosen. In Istanbul, 81 (88%) patients were treated with 300 mg, while 11 (12%) received 600 mg of omalizumab. In Barcelona, 7 (8.8%), 45 (56.3%), 17 (21.3%), and 11 (13.8%) patients received 150, 300, 450, and 600 mg of omalizumab, respectively. Urticaria control was achieved in 82.6% of the patients with 300 mg and in 8.7% of the patients with 600 mg in Istanbul, while it was achieved with 150 mg in 10%, with 300 mg in 48.8%, with 450 mg in 16.3%, and with 600 mg in 6.3% of the patients in Barcelona. In total, 123 (71.5%) patients responded to 150–300 mg and 26 (15.1%) to 450–600 mg. When responders to 150–300 mg (n = 123) were compared with responders to 450–600 mg (n = 26), BMI was found to be higher, and pre-omalizumab UCT was found to be lower in patients receiving updosed omalizumab (p = 0.029). Baseline data of the patients, especially BMI and pre-oma UCT, might be useful to determine if the patient will require higher doses of omalizumab. We recommend a stepwise approach starting from 450 mg and then updosing to 600 mg in CSU patients who do not respond or partially respond to 300 mg of omalizumab after 3–6 months of treatment.

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