Remibrutinib improves chronic spontaneous urticaria in patients irrespective of cu-index: results from phase 2b study

Introduction We explored the effect of remibrutinib (LOU064), a novel oral Bruton's Tyrosine Kinase inhibitor, in chronic spontaneous urticaria (CSU) patients by baseline CU-index. Methods In this Phase 2b study (NCT03926611), 311 CSU patients were equally randomized to remibrutinib 10mg once-daily (q.d.)/35mg q.d./100mg q.d./10mg twice-daily (b.i.d.)/25mg b.i.d./100mg b.i.d. or placebo for 12 weeks. Outcomes included changes in weekly Urticaria Activity Score (UAS7) by baseline CU-index-positive (≥10) and -negative (<10) at Weeks 4 and 12, and patients achieving UAS7=0 and UAS7≤6 by CU-index at Week 12. Results Of 311 patients, 34.4% were CU-index-positive at baseline. Reductions of mean UAS7 from baseline were higher in CU-index-positive vs -negative patients in all remibrutinib arms at Weeks 4 (−18.64 to −30.15 vs −12.82 to −19.85) and 12 (−18.91 to −32.50 vs −13.56 to −18.29). In the placebo arm, mean UAS7 reduction was higher in CU-index-negative vs -positive patients at Weeks 4 (−6.68 vs −1.25) and 12 (−9.06 vs −5.81). At Week 12, higher proportions of CU-index-positive vs -negative patients achieved UAS7=0 (31.6–54.5% vs 18.5–34.5%) and UAS7≤6 (50.0–72.7% vs 32.1–48.3%) in all remibrutinib arms. In the placebo arm, more CU-index-positive vs -negative patients achieved UAS7=0 (21.4% vs 11.1%); UAS7≤6 response was similar between subgroups (28.6% vs 29.6%) Table 1. Conclusion Remibrutinib (all doses) improved UAS7 regardless of baseline CU-index, with greater improvements in CU-index-positive vs -negative patients. More patients on remibrutinib achieved UAS7=0 and UAS7≤6 vs placebo, irrespective of baseline CU-index. Larger studies are required to confirm the findings from Phase 2b study. UAS7, weekly Urticaria Activity Score.