Phase 2 trial study demonstrated the safety and efficacy of remibrutinib in Sjögren’s syndrome

Bruton’s tyrosine kinase (BTK) inhibition is a novel pharmaceutical strategy under active investigation for treating inflammatory, allergy, and autoimmune diseases. Remibrutinib, an oral, covalent, highly selective, and potent BTK inhibitor, has shown significant pathway inhibition in human studies, demonstrating a favorable safety profile across the entire dose range. A recent randomized, double-blind, placebo-controlled phase 2 trial, published in the Annals of the Rheumatic Diseases, reported positive findings regarding both safety and efficacy in patients with moderate-to-severe Sjögren’s syndrome. 

The study conducted by Dörner et al. involved patients with moderate-to-severe Sjögren’s syndrome. Using a 1:1:1 randomization process, 73 eligible patients were assigned to one of three treatment groups: 25 patients to the remibrutinib 100 mg once daily group, 24 patients to the remibrutinib 100 mg twice daily group, and 24 patients to the placebo group. Over the 24-week period, remibrutinib significantly improved the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) score compared to placebo (ΔESSDAI -2.86, p=0.003). However, the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) score showed no treatment impact (ΔESSPRI 0.17, p=0.663). Remibrutinib exhibited a tendency to increase unstimulated salivary flow over 24 weeks when compared to a placebo. Throughout the 24-week period, remibrutinib demonstrated a positive safety profile in individuals with Sjögren’s syndrome. Notably, when remibrutinib replaced the placebo, there were significant changes in blood serum protein abundance and gene expression. 

Remibrutinib has shown promise in treating chronic spontaneous urticaria (CSU) in a phase 2 randomized controlled study, while maintaining a good safety profile. Since remibrutinib targets underlying B cell problems, it holds greater potential in treating Sjögren’s syndrome. The current study findings underscore the potential of remibrutinib as a treatment for Sjögren’s syndrome and lay the groundwork for further drug development. Extended treatment duration may be necessary to observe effects on patient-reported outcomes. 


Dörner T, Kaul M, Szántó A, Tseng JC, Papas AS, Pylvaenaeinen I, et al. 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. Ann Rheum Dis. 2023 Nov 6;ard-2023-224691.