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