Patients were randomized into three groups receiving 100 mg of remibrutinib twice daily (n=24), 100 mg of remibrutinib once daily (n=25) or placebo (n=24). Due to similarity in responses across doses, data from both dose groups of remibrutinib were compiled in the study results.
“At week 24, the study was positive for its primary end point,” said Dr. Dörner. “The change in active treatment with remibrutinib led to a reduction of the ESSDAI of 2.86, compared to placebo” (P=0.003).
Disappointingly, patient-reported outcomes were similar in the remibrutinib and placebo groups; disease scores declined in both groups during the study. This included analysis via ESSPRI, which did not show a difference in any of its three domains. The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and EuroQol-5 Dimensions, two other patient-reported outcomes, were also similar between the two groups.
However, Dr. Dörner pointed out that unstimulated salivary flow showed a tendency for improvement with remibrutinib. CXCL13, an important chemokine to attract T and B cells into lymphoid follicles and autoimmune tissues, was decreased in the remibrutinib group compared to the placebo group. Anti-SSA and anti-SSB antibodies also declined in the remibrutinib group, as did serum IgM and IgG.
In terms of safety concerns, remibrutinib was well tolerated. The incidence of adverse events was similar across the treatment groups, including one serious adverse event in each arm leading to study discontinuation. Adverse events of special interest, such as bleeding, infections and cytopenia, were equally distributed across the groups. Dr. Dörner also shared that the study highlighted no cardiovascular concerns, which can sometimes be a problem for other members of the BTK inhibitor drug class (e.g., no increased blood pressure, atrial fibrillation or prolongation of the QT interval on electrocardiogram.)4
Both ESSDAI and ESSPRI are validated measures commonly used as clinical trial end points, and it is difficult to know what to make of the discrepancy between the two outcomes. It is possible that treatment past 24 weeks may lead to eventual ESSPRI improvements. Some other Sjögren’s syndrome trials have shown a poor association between ESSDAI and ESSPRI, and ESSDAI may have greater responsiveness to disease changes than ESSPRI.8,9
Dr. Dörner concluded that, in sum, the evidence suggests that remibrutinib may prove to be an effective oral disease-modifying treatment for Sjögren’s syndrome, although this will need to be demonstrated through further studies.
