A randomized, placebo-controlled, dose-ranging study of single-dose omalizumab in patients with H1-antihistamine–refractory chronic idiopathic urticaria

Abstract

Proof-of-concept studies with omalizumab in patients with chronic idiopathic urticaria (CIU) have shown significant decreases in mean urticaria activity scores (UASs). We sought to evaluate the efficacy and safety of omalizumab in patients with CIU who remain symptomatic despite concomitant H(1)-antihistamine therapy. This phase II, prospective, double-blind, placebo-controlled, dose-ranging study investigated omalizumab in patients aged 12 to 75 years in the United States and 18 to 75 years in Germany with a UAS over 7 days (UAS7) of 12 or greater despite antihistamine therapy. Patients were randomized 1:1:1:1 to receive a single subcutaneous dose of 75, 300, or 600 mg of omalizumab or placebo added to a stable dose of H(1)-antihistamine. The primary efficacy outcome was change from baseline to week 4 in UAS7. Patients were followed for an additional 12 weeks to monitor safety. Ninety patients from the United States or Germany were enrolled. Both the 300-mg omalizumab group (-19.9 vs -6.9, P < .001) and the 600-mg omalizumab group (-14.6 vs -6.9, P = .047) showed greater improvement versus the placebo group in UAS7. No meaningful difference was observed for the 75-mg omalizumab group. Similar results were seen for key secondary end points of weekly hive and itch scores. Onset of effect occurred after 1 to 2 weeks. Omalizumab was well tolerated, and the incidence of adverse events was similar across treatment groups. This study demonstrated that a fixed dose of 300 or 600 mg of omalizumab provides rapid and effective treatment of CIU in patients who are symptomatic despite treatment with H(1)-antihistamines.