**2. Pivotal phase III trials with omalizumab in patients with CSU**

The first successful use of omalizumab for CU was reported by Boyce in 2006 [8]. The 3 essential phase III multicenter, randomized, double-blinded studies that led to the FDA indication for CSU were the ASTERIA I [9] and II [10], and GLACIAL [11] trials. These trials included a total of 733 patients on omalizumab 75, 150, or 300 mg at 4-week intervals and 242 patients were allocated in the placebo groups. Clinical efficacy of omalizumab in randomized controlled trials including these 3 pivotal trials are summarized in **Table 1**.

ASTERIA I was a 40-week trial included patients receiving either omalizumab 75 mg, omalizumab 150 mg, omalizumab 300 mg, or placebo given in 4-week intervals for a 24-week treatment period with 16 weeks of follow-up [9]. The patients who had failed H1 antihistamine treatment at licenced doses were enrolled. All 3 doses of omalizumab met their primary efficacy endpoint of a reduction in weekly itch severity score (ISS) at 12 weeks compared with baseline (−6.46 with omalizumab 75 mg, −6.66 with omalizumab 150 mg, and − 9.40 with omalizumab 300 mg). The omalizumab 300 mg group achieved the minimally important difference in weekly ISS at a significantly shorter duration compared with the other omalizumab doses. However, urticaria symptoms returned to placebo levels after omalizumab was discontinued in all treatment groups during the follow-up period.

ASTERIA II was a 28-week trial that included 12 weeks of therapy with either omalizumab 75 mg, 150 mg, or 300 mg, or placebo in 4-week intervals with a 16-week follow-up period [10]. The patients having already failed treatment with approved doses of H1 antihistamines were included. The group of omalizumab 75 mg was failed to show significant difference in weekly ISS at 12 weeks compared with the placebo group. The omalizumab 150 mg and 300 mg groups reached significance for their primary end point of a mean change from baseline in weekly ISS at 12 weeks (−8.1 with omalizumab 150 mg and − 9.8 with omalizumab 300 mg), as compared with placebo. The proportion of patients who had complete symptom control was 16%, 22%, 44%, and 5% for omalizumab 75 mg, 150 mg, 300 mg, and placebo groups, respectively. During the 16-week follow-up period, the ISS for all omalizumab doses increased to levels similar to those of the placebo group.

GLACIAL trial included patients who had failed H1 antihistamines at up to 4 times the approved doses in addition to approved doses of leukotriene receptor antagonists or H2 antihistamines [11]. These patients were given either omalizumab 300 mg or placebo every 4 weeks for 24 weeks followed by a 16-week observation period. The weekly ISS at week 12 compared with baseline was significantly improved in the omalizumab 300 mg group compared with placebo (−8.6 with omalizumab 300 mg). All the other secondary efficacy end points also met


*The Use of Omalizumab in Chronic Urticaria: Available Data and Future Aspects of Anti-IgE… DOI: http://dx.doi.org/10.5772/intechopen.97226*


#### **Table 1.**

*Clinical efficacy of omalizumab in randomized controlled trials.*

significance for the omalizumab group including change in weekly urticaria activity score (UAS7), Dermatology Life Qualirty Index, and proportion of patients who were itch and hive free. As with both ASTERIA trials, the effects of omalizumab appeared not to be permanent, and weekly ISS increased to placebo levels after discontinuing omalizumab treatment.

24 W

Recently, several systematic analyses based on various randomized controlled trials [9–19] to evaluate the effects of omalizumab for patients with CSU have been reported [3, 20–22]. These systematic reviews have provided high-quality of evidence on that omalizumab is effective in the treatment of antihistaminerefractory CSU independent of monthly dose [3, 22]. The dosage of 300 mg every 4 weeks is found to achieve better results in reductions of disease activity scores and in improvement of disease-specific quality of life. However, a recent meta-analysis analyzed minimal important differences in urticaria outcome measures, such as UAS7, ISS7, and quality of life demonstrated that omalizumab 300 mg resulted in clinically meaningful improvement of all the outcome measures, whereas

*The Use of Omalizumab in Chronic Urticaria: Available Data and Future Aspects of Anti-IgE… DOI: http://dx.doi.org/10.5772/intechopen.97226*

omalizumab 150 mg failed to prove clinically meaningful improvement in any of them as compared with standard of care [20].
