CSU disease activity band shift after long-term treatment with remibrutinib in the phase 3 REMIX-1 & REMIX-2 studies

Abstract

Prérequis/contexte

Remibrutinib (REM), a novel oral, highly selective Bruton's tyrosine kinase inhibitor, has previously shown superior efficacy vs placebo (pbo) at week 12 and favourable safety in the 24-week double-blind (DB) period of Phase 3 studies (REMIX-1 and -2) in patients with chronic spontaneous urticaria (CSU) inadequately controlled by H1-antihistamines.

Objectifs

The objective of this analysis was to explore the shift in weekly urticaria Activity Score (UAS7) bands after treatment with REM vs pbo in the REMIX studies.

Méthodes

Patients with CSU were randomized 2: 1 to REM 25 mg twice daily (bid) or pbo over a 24-week DB treatment period, followed by 28 weeks of open-label treatment with REM 25 mg bid (patients on pbo transitioned to REM at week 24). CSU disease activity bands are defined by five standard UAS7 ranges: UAS7: 28–42 (severe), UAS7: 16– < 28 (moderate), UAS7: >6– < 16 (mild), UAS7: >0–6 (well-controlled) and UAS7 = 0 (complete response).

Résultats/discussions

This pooled analysis included 606 patients from the REM and 306 from Pbo arms. At baseline, 215 (35.5%) and 386 (63.7%) patients from REM and 122 (39.9%) and 181 (59.2%) from Pbo had moderate and severe CSU disease activity, respectively. In the REM arm, 63.7% patients were in the severe band at baseline, the number dropped to 24.9, 17.2, 9.1, 7.8, and 8.1% at weeks 1, 2, 12, 24 and 52, respectively. Similarly, of the 35.5% of patients in the moderate band at baseline, the number dropped to 30.7, 24.1, 10.6, 7.9 and 7.3% at weeks 1, 2, 12, 24 and 52, respectively. There were no patients in the well-controlled disease band at baseline; however, the numbers increased from 11.4 and 15.3% at weeks 1 and 2 to 17.8% at week 12, followed by 14.9% at week 24 and 13.4% at week 52. Notably, proportion of patients who showed complete response increased from 0.3% at week 1 to 16.2% at week 2, followed by 28.5% at week 12, 33.7% at week 24 and 35.1% at week 52. At the end of week 52, patients who switched to REM after the Pbo reached similar band shifts.

Conclusion

REM reduced CSU disease activity as early as week 1 in patients with CSU, and the fast response was sustained over the long-term (52 weeks) treatment.