Study Design, Outcomes And Sample Size

This single-blinded, one-arm, repeated-measures, single-center study was conducted at a specialist urticaria clinic (Figure 1). The inclusion criteria, mentioned in S-Table 1, were SGAH-unresponsive adult CSU subjects with a weekly urticaria activity score (UAS7) of ≥4 and pruritus score of ≥2. The primary endpoint was the percentage of CSU subjects with a significant clinical response to 3 doses of benralizumab 30mg versus placebo. Clinical response was measured by UAS7 (range 0-42), a validated questionnaire that quantifies wheal and pruritus severity over seven days week each recorded on a 0-3 scale.21 For this study, a significant clinical response was defined as a minimally detectable change (MDC) in UAS7 of 14 from the baseline score. For an MDC of 14 with a minimum sample size of 6 CSU subjects, the power of the study was calculated to be >0.9 (alpha=0.05). All urticaria medications were discontinued during the study period except rescue medications. A medication history for use of SGAHs and other urticarial therapies including biologics were obtained from all subjects at their baseline visit.
Secondary endpoints included the percent reduction in inflammatory cell counts in peripheral blood and skin, and the differential gene expression using RNA-sequencing in peripheral blood pre- and post-treatment with benralizumab. An objective response to benralizumab was determined by measuring differences of inflammatory cell infiltrates (lymphocytes, basophils) in skin biopsies at visit 2 (post-placebo/pre-benralizumab) vs. visit 5 (4 weeks post-benralizumab), and relative white cell counts in peripheral blood sampled at baseline and at each post-treatment visit. An exploratory endpoint was the validated chronic urticaria quality of life questionnaire (CU-QoL summarized in S-Table 2).25,26