Efficacy and Safety of Remibrutinib, a Selective Potent Oral BTK Inhibitor, in Sjögren's Syndrome: Results from a Randomised, Double-blind, Placebo-controlled Phase 2 Trial

Overview

Journal Ann Rheum Dis

Specialty Rheumatology

Date 2023 Nov 6

PMID 37932009

Authors

Thomas Dorner

Martin Kaul

Antonia Szanto

Jui-Cheng Tseng

Athena S Papas

Ilona Pylvaenaeinen

Malika Hanser

Nasri Abdallah

Andrea Grioni

Aida Santos Da Costa

Enrico Ferrero

Peter Gergely

Rainer Hillenbrand

Alexandre Avrameas

Bruno Cenni

Richard M Siegel

Affiliations

Soon will be listed here.

Abstract

Objectives: To evaluate the safety and efficacy of remibrutinib in patients with moderate-to-severe Sjögren's syndrome (SjS) in a phase 2 randomised, double-blind trial (NCT04035668; LOUiSSE (LOU064 in Sjögren's Syndrome) study).

Methods: Eligible patients fulfilling 2016 American College of Rheumatology/European League Against Rheumatism (EULAR) criteria for SjS, positive for anti-Ro/Sjögren's syndrome-related antigen A antibodies, with moderate-to-severe disease activity (EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) (based on weighted score) ≥ 5, EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) ≥ 5) received remibrutinib (100 mg) either one or two times a day, 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 patients with SjS over 24 weeks compared with placebo (ΔESSDAI -2.86, p=0.003). No treatment effect was observed in ESSPRI score (ΔESSPRI 0.17, p=0.663). There was a trend towards improvement of unstimulated salivary flow with remibrutinib compared with placebo over 24 weeks. Remibrutinib had a favourable safety profile in patients with SjS over 24 weeks. Remibrutinib induced significant changes in gene expression in blood, and serum protein abundance compared with placebo.

Conclusions: These data show preliminary efficacy and favourable safety of remibrutinib in a phase 2 trial for SjS.

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