With a pressing need for some disease-modifying treatment that works in Sjögren’s syndrome it is great to report a positive trial.
We have a pressing need for some disease-modifying treatment that works in Sjögren’s Syndrome (SjS), so it is great to report a positive trial!
As a B-cell driven disease, Bruton’s tyrosine kinase (BTK) is thought to play a crucial role. Remibrutinib (LOU064) is an oral, covalent, highly specific BTK inhibitor. It has been found to be efficacious with favourable safety in chronic urticaria.
The LOUiSSe study is a Phase 2a, double-blind, RCT studying the medication in SjS.
73 patients were randomized to receive remibrutinib 100 mg bd (n=24), 100 mg daily (n=25), or placebo (n=24) between Aug 2019 and May 2021. Only 2 patients were men.
Groups were representative of patients with SjS (2016 ACR/EULAR criteria) and were generally balanced. The mean ESSDAI score was 9-10 which Dr Thomas Dorner, the presenter, explained represented a moderate to severe group.
The completion rate was lower in the treated population, 70.8% vs 68% vs 87% respectively. The presenter commented that there was no pattern in the reasons for discontinuation.
At week 24, the study clearly met its primary endpoint with a significant improvement in ESSDAI score. The difference in change in ESSDAI was -2.86 (p=0.003) between Remibrutinib-treated patients and placebo. Numerical improvement was seen at every time point. No obvious difference in efficacy was seen between the 2 doses.
However, there was no treatment effect on the secondary end-point of the ESSPRI, an index looking at patient symptoms with subdomains of dryness, pain, fatigue. When queried about this, Dr Dorner answered that the ESSPRI was much more subjective than the ESSDAI and might need longer treatment time to show a difference.
There was a trend to improvement with unstimulated salivary flow rate. IgG and IgM levels declined in the treatment arm and remained within the normal range, while anti-SSA and -SSB autoantibodies followed a decreasing trend, similar to total IgG levels.
With the safety analysis, 87.8% of the active treatment group vs 83.3% of the placebo reported adverse events, without any significant differences.
Remibrutinib seems potentially effective and importantly, well tolerated, which should mean that we will see further studies.
