Efficacy of Second-Line Treatments in Chronic Urticaria Refractory to Standard Dose Antihistamines

PURPOSE: The prevalence of chronic urticaria (CU) is increasing worldwide, and it imposes a major burden on patients. Few studies have evaluated the efficacy of second-line treatments of CU, particularly for patients being considered for costly third-line treatments such as omalizumab. We compared the efficacy and safety of second-line treatments of CU refractory to standard doses of nonsedating H(1)-antihistamines (nsAHs). METHODS: This 4-week, prospective, randomized, open-label trial divided patients into 4 treatment groups: 4-fold updosing of nsAHs, multiple combination of 4 nsAHs, switching to other nsAHs, and adjunctive H(2)-receptor antagonist. The clinical outcomes included urticaria control status, symptoms, and rescue medication use. RESULTS: This study included 109 patients. After 4 weeks of second-line treatment, urticaria was well-controlled, partly controlled, and uncontrolled in 43.1%, 36.7%, and 20.2% of patients, respectively. Complete control of CU was achieved in 20.4% of patients. Among the patients with high-dose nsAHs, the proportion with well-controlled status was higher compared to the patients who received standard doses (51.9% vs. 34.5%, P = 0.031). No significant difference was observed in the proportion of well-controlled cases between the updosing and combination treatment groups (57.7% vs. 46.4%, P = 0.616). However, increasing the dose of nsAHs 4-fold was associated with a higher rate of complete symptom control compared to multiple combination treatment with 4 nsAHs (40.0% vs. 10.7%, P = 0.030). Logistic regression analysis confirmed the higher efficacy of updosing of nsAHs for complete control of CU compared to the other treatment strategies (odds ratio, 0.180; P = 0.020). CONCLUSIONS: In patients with CU refractory to standard doses of nsAHs, both updosing of nsAHs 4-fold and multiple combination treatment with 4 nsAHs increased the rate of well-controlled cases without causing significant adverse effects. Updosing of nsAHs is more effective for complete CU control than combination treatment.