EADV 2025: Remibrutinib Shows Immunological Impact in CSU Patients

At the European Academy of Dermatology and Venereology (EADV) Congress 2025 in Paris, France, new data were presented on the immunomodulatory effects of remibrutinib, a highly selective Bruton’s tyrosine kinase (BTK) inhibitor, in patients with chronic spontaneous urticaria (CSU). The findings add to the growing body of evidence that remibrutinib not only controls clinical symptoms but may also influence underlying autoimmune mechanisms in subsets of patients.¹

Background

Chronic spontaneous urticaria is characterized by recurrent wheals, angioedema, or both for more than 6 weeks without identifiable triggers. For a significant proportion of patients, the condition has an autoimmune basis, often classified as type IIb autoimmune CSU. In these patients, elevated serum IgG autoantibodies against thyroid peroxidase (TPO), thyroglobulin (TG), or the high-affinity IgE receptor (FcεRI) have been reported. Current treatment strategies, principally second-generation H1-antihistamines and biologics such as omalizumab, are often insufficient in refractory cases.²

Remibrutinib, an oral BTK inhibitor, has demonstrated superior efficacy versus placebo with a favorable safety profile in the pivotal phase 3 REMIX-1 and REMIX-2 trials. Because BTK plays a central role in B cell signaling and autoantibody production, the present analysis investigated whether remibrutinib affects IgG autoantibody levels in CSU.

Study Design and Methods

Investigators analyzed 1,191 samples from 397 patients enrolled in the REMIX-1 and REMIX-2 trials (NCT05030311, NCT05032157). Patients were randomized to receive remibrutinib 25 mg twice daily or placebo for 24 weeks, followed by open-label remibrutinib through week 52.

Serum IgG autoantibodies were measured using a bead-based cytometric assay, focusing on anti-FcεRI, anti-TPO, and anti-TG antibodies. In addition, soluble CD23 (a marker of B cell activation) was quantified, and B cell subsets were profiled by flow cytometry at baseline, week 4, week 12, week 24, and week 52. Subgroup analyses were conducted according to Chronic Urticaria Index (CUI) status, a test that identifies autoantibody-positive patients.

Results

At baseline, patients with positive CUI (CUI+) exhibited significantly higher levels of CSU-associated autoantibodies compared with CUI-negative (CUI–) patients. Following treatment with remibrutinib, CUI+ patients demonstrated significant reductions in FcεRI- and TG-specific IgG levels compared with placebo at week 24.

Patients initially randomized to placebo who switched to remibrutinib at week 24 showed comparable decreases in IgG autoantibody levels by week 52. Importantly, CUI+ patients also exhibited higher baseline soluble CD23 levels, which declined during treatment. The reduction in autoantibody levels was paralleled by decreases in circulating non-switched memory B cells and soluble CD23 concentrations, suggesting a link between BTK inhibition and modulation of autoreactive B cell activity.

Clinical Implications

These findings suggest that remibrutinib may address a key pathogenic mechanism in autoimmune/type IIb CSU by reducing disease-associated IgG autoantibody production. While remibrutinib has already established clinical efficacy in reducing symptoms and improving quality of life for patients inadequately controlled with antihistamines, this analysis highlights a potential disease-modifying effect in autoantibody-positive patients.

Nevertheless, researchers noted these results should be interpreted cautiously. The reductions in autoantibody levels were largely confined to the CUI+ subgroup, emphasizing the heterogeneity of CSU. It remains to be determined whether such immunological changes translate into long-term remission or altered disease course.

Conclusion

The EADV 2025 presentation supports the hypothesis that BTK inhibition with remibrutinib not only alleviates symptoms of CSU but may also reduce pathogenic IgG autoantibodies and associated B cell activation markers, particularly in patients with an autoimmune profile. For clinicians managing refractory CSU, these data underscore the potential for remibrutinib to provide both symptomatic relief and immunological modulation, pending further confirmatory studies.

References

1. Metz M. Remibrutinib decreases specific IgG autoantibody levels in patients with chronic spontaneous urticaria. Presented at: European Academy of Dermatology and Venereology Congress 2025; September 17-20, 2025; Paris, France.
2. Kolkhir P, Fok JS, Kocatürk E, et al. Update on the treatment of chronic spontaneous urticaria. Drugs. 2025;85(4):475-486. doi:10.1007/s40265-025-02170-4