Remibrutinib oral therapy effective against Sjogren's syndrome

Over the course of 24 weeks, remibrutinib was well tolerated by Sjögren's syndrome (SS) patients and had a favorable safety profile. The findings were presented by Thomas Dörner in the American College of Rheumatology Convergence 2022.

Patients with SS are 15–20 times more likely to develop B-cell lymphoma, a potentially fatal consequence. Remibrutinib is an oral, covalent, and extremely effective Bruton's tyrosine kinase inhibitor (BTK). BTK is essential for B-cell receptor and Fc receptor signaling and is expressed in cells of the innate and adaptive immune systems, including B cells. 

This randomized, double-blind, placebo-controlled phase 2 study recruited patients with moderate to severe Sjögren's syndrome (SS) who had a baseline EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score of 5, an anti-Ro/SSA antibody positivity 3 months prior to screening, and an unstimulated whole salivary flow rate of >0 mL/min. The safety of remibrutinib in SS patients, as well as its influence on changes from baseline in ESSDAI, salivary flow, and patient reported outcomes (PRO), were investigated.

The key findings of this study were:

1. Between August 2019 and May 2021, 73 patients were randomly assigned to receive remibrutinib 100 mg bid (n=24), 100 mg qd (n=25), or placebo (n=24).

2. Only two of the patients were guys. The average (standard deviation) age was 51.8 (13.34) years.

3. In terms of demographic and disease-related baseline data, the groups were generally balanced.

4. The occurrence of adverse events (AEs) was comparable among groups. There were no significant adverse events recorded.

5. Infections were the most often reported adverse event by system organ class, with rates comparable in the remibrutinib and placebo groups.

6. There were no significant liver abnormalities detected in any of the groups.

7. At week 24, remibrutinib resulted in a significantly significant improvement in ESSDAI score compared to placebo, with numerical improvement over placebo at all time points.

8. When compared to placebo, unstimulated salivary flow improved with remibrutinib.

9. Total serum IgG and IgM levels fell from baseline but remained within acceptable limits. Autoantibodies against SS-A and SS-B followed the same pattern as total IgG.

10. PROs such as ESSPRI, Functional Assessment of Chronic Illness Therapy-Fatigue, and EuroQol-5 Dimension were comparable across the remibrutinib and placebo groups.

In conclusion, these findings point to remibrutinib as the first successful oral disease-modifying treatment for SS. PROs, like ESSPRI, may require a longer period of time to reveal advantages. More research is needed to validate the efficacy of remibrutinib therapy in SS.

Reference:

Dörner T, Szántó A, Tseng J, Kaul M, Pylvaenaeinen I, Hanser M, Abdallah N, Cenni B, Siegel R. Remibrutinib (LOU064) in Sjögren's Syndrome: Safety and Efficacy Results from a 24‑Week Placebo-controlled Proof-of-Concept Study [abstract]. ACR Convergence 2022; In American College of Rheumatology.