medwireNews: Remibrutinib, an oral Bruton’s tyrosine kinase (BTK) inhibitor, has shown potential for the treatment of Sjögren's syndrome in a phase 2 study.
“Inhibition of BTK has emerged as a potential therapeutic option for a number of autoimmune diseases,” including chronic urticaria, presenter Thomas Dörner (Charité – Universitätsmedizin Berlin, Germany) told delegates at ACR Convergence 2022 in Philadelphia, Pennsylvania, USA.
In the latest phase 2 study – LOU064 in Sjögren’s Syndrome (LOUiSSe) – treatment with remibrutinib resulted in a significant 2.86-point greater least squares mean reduction in EULAR Sjögren’s syndrome Disease Activity Index (ESSDAI) score at week 24 compared with placebo, from mean baseline values of 9 and 10 points, respectively.
The difference between the two treatments was apparent from week 2 to 4 and sustained over the 24 weeks, Dörner highlighted.
A total of 73 patients, aged 18 to 75 years, with moderate-to-severe disease participated in the study and Dörner emphasized that “this was a very representative Sjögren's syndrome population.”
To meet the study criteria, the patients all had to have an ESSDAI score of at least 5 points on eight domains, a EULAR Sjögren’s syndrome Patient Reported Index (ESSPRI) score of at least 5 points, an unstimulated salivary flow rate above 0 mL/min, and be seropositive for anti-Ro/SSA antibodies at the time of screening or in the 3 months prior.
The patients were randomly assigned to receive one of two remibrutinib dosing regimens – 100 mg once or twice daily – or placebo. However, due to similar outcomes in the two remibrutinib groups they were combined in the final analysis, giving a total of 49 patients in the remibrutinib group versus 24 in the placebo group.
In addition to significant improvement in the primary outcome of change in ESSDAI score, remibrutinib was associated with a trend toward improved unstimulated salivary flow and a reduction in CXCL13 levels, as a biomarker of disease activity, that was not seen with placebo.
There were also greater reductions from baseline in immunoglobulin (Ig)G and most notably IgM levels with remibrutinib, with both staying within the normal range, but neither group experienced a change in IgA levels.
“These changes, in particular for IgG, somehow correlated with changes of the disease characteristic autoantibodies,” noted Dörner, who reported greater reductions in levels of all three autoantibodies (SS-B, SSA-Ro-60, and SSA-Ro-52/Trim21) from baseline to week 24 with remibrutinib compared with placebo.
“This confirms […] the impact of the BTK inhibitor on the disease-relevant autoantibodies,” he said.
By contrast, patient-reported outcomes, including ESSPRI score, improved to a similar degree in the two treatment groups and there was no differentiation between the two treatments in terms of the ESSPRI subdomains of dryness, pain, and fatigue.
“The safety and tolerability [of remibrutinib] over 24 weeks did not substantially differ from the placebo group,” said Dörner. The adverse event (AE) rates were 87.8% with remibrutinib and 83.3% with placebo, with infections and infestations the most common events.
There were nine AEs leading to drug discontinuation; seven among patients taking remibrutinib and two among those taking placebo.
Dörner concluded: “The LOUiSSe study suggests remibrutinib as a potentially effective oral disease-modifying therapy for Sjögren's, which will be established in longer-term studies.”
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