A recent Phase 2 clinical trial, published in the Annals of Rheumatic Diseases, has revealed encouraging results for remibrutinib, an experimental drug, in treating moderate-to-severe Sjögren’s syndrome (SjS). The double-blind, randomized LOUiSSE study (LOU064 in Sjögren’s Syndrome) assessed the safety and efficacy of remibrutinib in improving disease outcomes for patients with this complex autoimmune disorder.
Remibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor, which works by blocking the BTK pathway and preventing the release of histamine. The trial included patients who met the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for Sjögren’s syndrome and tested positive for anti-Ro antibodies. Participants had moderate-to-severe disease activity, with baseline EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) scores of ≥5 and EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) scores of ≥5. Over a 24-week period, patients were randomly assigned to receive either remibrutinib (100 mg once or twice daily) or a placebo.
The primary aim of the study was to assess changes in ESSDAI, a key measure of disease activity, after 24 weeks. Secondary endpoints included changes in ESSDAI and ESSPRI scores, the safety profile of remibrutinib, and exploratory measures such as salivary flow rate and immune-related biomarkers. The results demonstrated that remibrutinib significantly reduced disease activity, with a mean change in ESSDAI of -2.86 (p=0.003) compared to placebo, suggesting potential efficacy in controlling systemic inflammation in moderate-to-severe Sjögren’s syndrome. However, there was no significant improvement in ESSPRI scores, which track patient-reported symptoms like dry mouth, dry eyes, and fatigue. The change in ESSPRI was modest (Δ 0.17, p=0.663), indicating that while the drug helped manage disease activity, it did not substantially alleviate the subjective symptoms.
In addition, remibrutinib showed a trend towards improving unstimulated salivary flow rate, a hallmark symptom of Sjögren’s syndrome. The drug’s safety profile was favorable, with no major adverse events and side effects similar to those observed in the placebo group. Gene expression and serum protein analyses suggested that remibrutinib might influence immune pathways involved in Sjögren’s syndrome, offering insights into its potential therapeutic mechanisms.
A study by Jain et al. demonstrated that remibrutinib maintained a consistently favorable safety profile, combined with rapid and sustained efficacy, for up to 52 weeks in patients with chronic spontaneous urticaria. Most treatment-emergent adverse events were mild to moderate and unrelated to remibrutinib by the investigators. The three most common treatment-emergent adverse events reported were infections (30.9%), skin and subcutaneous tissue disorders (26.8%), and gastrointestinal disorders (16.5%).
These promising findings suggest that remibrutinib could become a valuable treatment for patients with moderate-to-severe Sjögren’s syndrome, although larger, longer-term studies are needed to confirm its efficacy and potential role as a cornerstone therapy. Given the limited treatment options available for this condition, the LOUiSSE trial provides hope for new therapeutic alternatives in the future.
Reference
- Dörner T, Kaul M, Szántó A, Tseng JC, Papas AS, Pylvaenaeinen I, et al. Efficacy and safety of remibrutinib, a selective potent oral BTK inhibitor, in Sjögren’s syndrome: results from a randomised, double-blind, placebo-controlled phase 2 trial. Annals of the Rheumatic Diseases. 2024 Mar 1;83(3):360–71.
- Maurer M, Berger W, Giménez-Arnau A, Hayama K, Jain V, Reich A, et al. Remibrutinib, a novel BTK inhibitor, demonstrates promising efficacy and safety in chronic spontaneous urticaria. Journal of Allergy and Clinical Immunology. 2022 Dec 1;150(6):1498-1506.e2.
- Jain V, Giménez-Arnau A, Hayama K, Reich A, Carr W, Tillinghast J, et al. Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks. Journal of Allergy and Clinical Immunology. 2024 Feb 1;153(2):479-486.e4.