Remibrutinib improves chronic spontaneous urticaria in patients with low or high ige

IntroductionBaseline 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.MethodsIn 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.ResultsThis 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).ConclusionRemibrutinib 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.