REMIBRUTINIB IMPROVES CHRONIC SPONTANEOUS URTICARIA IN PATIENTS IRRESPECTIVE OF CU-INDEX: RESULTS FROM PHASE 2B STUDY

Abstract

<h3>Introduction</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> Of 311 patients, 34.4% were CU-index-positive at baseline. Reductions of mean UAS7 from baseline were higher in CU-index-positive <i>vs</i> -negative patients in all remibrutinib arms at Weeks 4 (−18.64 to −30.15 <i>vs</i> −12.82 to −19.85) and 12 (−18.91 to −32.50 <i>vs</i> −13.56 to −18.29). In the placebo arm, mean UAS7 reduction was higher in CU-index-negative <i>vs</i> -positive patients at Weeks 4 (−6.68 <i>vs</i> −1.25) and 12 (−9.06 <i>vs</i> −5.81). At Week 12, higher proportions of CU-index-positive <i>vs</i> -negative patients achieved UAS7=0 (31.6–54.5% <i>vs</i> 18.5–34.5%) and UAS7≤6 (50.0–72.7% <i>vs</i> 32.1–48.3%) in all remibrutinib arms. In the placebo arm, more CU-index-positive <i>vs</i> -negative patients achieved UAS7=0 (21.4% <i>vs</i> 11.1%); UAS7≤6 response was similar between subgroups (28.6% <i>vs</i> 29.6%) Table 1. <h3>Conclusion</h3> Remibrutinib (all doses) improved UAS7 regardless of baseline CU-index, with greater improvements in CU-index-positive <i>vs</i> -negative patients. More patients on remibrutinib achieved UAS7=0 and UAS7≤6 <i>vs</i> placebo, irrespective of baseline CU-index. Larger studies are required to confirm the findings from Phase 2b study. UAS7, weekly Urticaria Activity Score.