Dörner, Thomas, Kaul, Martin, Szántó, Antónia, Jui-Cheng, Tseng, Papas, Athena, Pylvaenaeinen, Ilona, Hanser, Malika, Abdallah, Nasri, Grioni, Andrea, Santos da Costa, Aida, Ferrero, Enrico, Gergely, Peter, Hillenbrand, Rainer, Avrameas, Alexandre, Cenni, Bruno and Siegel, Richard (2023) Efficacy and safety of remibrutinib, a selective, potent oral BTK inhibitor, in Sjögren’s syndrome. Annals of Rheumatic Diseases.

Abstract

Objectives To evaluate the safety and efficacy of remibrutinib in patients with moderate to severe SjS in a Phase 2 randomised, double-blind, trial.
Methods Eligible patients (moderate to severe SjS [classification according to 2016 ACR/ /European League Against Rheumatism (EULAR) criteria]; EULAR Sjögren’s Syndrome Disease Activity Index [ESSDAI] (based on weighted score) ≥ 5, EULAR Sjögren’s Syndrome Patient Reported Index [ESSPRI] ≥ 5; unstimulated salivary flow rate of > 0 mL/min) received remibrutinib (100 mg) either once or twice daily, or placebo for the 24-week study treatment period. The primary endpoint was change from baseline in ESSDAI at Week 24. Key secondary endpoints included change from baseline in ESSDAI over time, change from baseline in ESSPRI over time and safety of remibrutinib in SjS. Key exploratory endpoints included changes to the salivary flow rate, soluble biomarkers, blood transcriptomic and serum proteomic profiles.
Results Remibrutinib significantly improved ESSDAI score in SjS patients over 24 weeks compared with placebo (ΔESSDAI −2.86, P=0.003). No treatment effect was observed in ESSPRI score. There was a trend towards improvement of unstimulated salivary flow with remibrutinib compared with placebo over 24 weeks. Post-hoc analysis showed a strong effect on Sjögren’s Tool for Assessing Response (STAR) at 24 weeks in the remibrutinib groups. Remibrutinib induced significant changes in gene expression in blood as well as in serum protein abundance compared with placebo.
Conclusions These data show preliminary efficacy and favorable safety of remibrutinib in a Ph2 trial for SjS.

Item Type:	Article
Date Deposited:	25 Nov 2023 00:45
Last Modified:	25 Nov 2023 00:45
URI:	https://oak.novartis.com/id/eprint/50616