Efficacy and safety of remibrutinib, a selective potent oral BTK inhibitor, in Sjogren's syndrome: results from a randomised, double-blind, placebo-controlled phase 2 trial.
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Dorner T, Kaul M, Szanto A, Tseng JC, Papas AS, Pylvaenaeinen I, Hanser M, Abdallah N, Grioni A, Santos Da Costa A, Ferrero E, Gergely P, Hillenbrand R, Avrameas A, Cenni B, Siegel RM
Efficacy and safety of remibrutinib, a selective potent oral BTK inhibitor, in Sjogren's syndrome: results from a randomised, double-blind, placebo-controlled phase 2 trial.
Ann Rheum Dis. 2024 Feb 15;83(3):360-371. doi: 10.1136/ard-2023-224691.
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- 37932009 [ View in PubMed]
- Abstract
OBJECTIVES: To evaluate the safety and efficacy of remibrutinib in patients with moderate-to-severe Sjogren's syndrome (SjS) in a phase 2 randomised, double-blind trial (NCT04035668; LOUiSSE (LOU064 in Sjogren's Syndrome) study). METHODS: Eligible patients fulfilling 2016 American College of Rheumatology/European League Against Rheumatism (EULAR) criteria for SjS, positive for anti-Ro/Sjogren's syndrome-related antigen A antibodies, with moderate-to-severe disease activity (EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) (based on weighted score) >/= 5, EULAR Sjogren'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 (DeltaESSDAI -2.86, p=0.003). No treatment effect was observed in ESSPRI score (DeltaESSPRI 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.