Efficacy and safety of remibrutinib, a selective potent oral BTK inhibitor, in Sj?gren's syndrome: results from a randomised, double-blind, placebo-controlled phase 2 trial

Objectives To evaluate the safety and efficacy of remibrutinib in patients with moderate-to-severe Sj & ouml;gren's syndrome (SjS) in a phase 2 randomised, double-blind trial (NCT04035668; LOUiSSE (LOU064 in Sj & ouml;gren's Syndrome) study).Methods Eligible patients fulfilling 2016 American College of Rheumatology/European League Against Rheumatism (EULAR) criteria for SjS, positive for anti-Ro/Sj & ouml;gren's syndrome-related antigen A antibodies, with moderate-to-severe disease activity (EULAR Sj & ouml;gren's Syndrome Disease Activity Index (ESSDAI) (based on weighted score) >= 5, EULAR Sj & ouml;gren'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 (Delta ESSDAI -2.86, p=0.003). No treatment effect was observed in ESSPRI score (Delta ESSPRI 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.