REMIBRUTINIB IMPROVES CHRONIC SPONTANEOUS URTICARIA IN PATIENTS WITH LOW OR HIGH IGE

Abstract

<h3>Introduction</h3> Baseline IgE levels in patients with chronic spontaneous urticaria (CSU) may correlate to treatment outcomes. We investigated response rates to remibrutinib, a highly selective oral Bruton's tyrosine kinase inhibitor, in patients with CSU by baseline IgE. <h3>Methods</h3> In this Phase IIb, 12-week trial patients with CSU (weekly Urticaria Activity Score [UAS7] ≥16) were randomized to one of six doses of remibrutinib or placebo. Outcomes at Week 12 included UAS7 change from baseline (CFB) and percentage of patients achieving UAS7=0 and UAS7≤6; all data are presented by IgE ≤43IU/mL and >43IU/mL subgroups. <h3>Results</h3> This analysis included 304 patients. Approximately 70% of patients were in the IgE >43IU/mL subgroup. Median UAS7 CFB in IgE ≤43IU/mL patients (n=92) was -28.5, -28.3, -22.3, -24.5, -33.0, -23.0 and -1.5, and in IgE >43IU/mL patients (n=212) was -17.5, -14.3, -15.3, -15.8, -19.0, -24.5 and -8.0 in remibrutinib 10mg q.d., 35mg q.d., 100mg q.d., 10mg b.i.d., 25mg b.i.d., 100mg b.i.d. and placebo, respectively. The percentage of patients achieving UAS7=0 and UAS7≤6 was higher in IgE ≤43 IU/mL patients vs. IgE >43 IU/mL patients (Figure). <h3>Conclusion</h3> Remibrutinib improved UAS7 in all patients, regardless of baseline IgE. UAS7 improvements were larger in IgE ≤43IU/mL vs. >43IU/mL patients with all remibrutinib doses. More patients achieved UAS7=0 with any remibrutinib dose vs. placebo with any baseline IgE level. Overall, remibrutinib 25mg b.i.d. provided the greatest improvements in UAS7 for both UAS7=0 and UAS7≤6. This subgroup analysis shows the potential for remibrutinib to improve CSU activity control also in patients with baseline IgE ≤43IU/mL.