Remibrutinib Lowers Specific IgG Autoantibody Levels in Individuals with CSU

Remibrutinib treatment of chronic spontaneous urticaria (CSU) decreases abnormally elevated disease-related immunoglobulin G (IgG) autoantibodies, according to recent data, and this is particularly true among patients with a positive Chronic Urticaria Index (CUI).1

These late-breaking findings were presented during the European Academy of Dermatology and Venereology (EADV) 2025 Congress in Paris by trial investigator Martin Metz, MD, a professor of dermatology at the Institute of Allergology at the. Charité – Universitätsmedizin in Berlin. Metz and his team noted in their research that CSU is defined by the recurrent appearance of pruritic wheals and/or angioedema without the presence of identifiable triggers. CSU is also known to persist for over 6 weeks.

In a subset of individuals with autoimmune or type 2b CSU, the common observance of elevated serum IgG autoantibodies targeting thyroid peroxidase (TPO), thyroglobulin (TG), or the high-affinity IgE receptor (FcεRI) were noted by Metz et al. Superior efficacy over placebo has been demonstrated by remibrutinib, an oral Bruton’s tyrosine kinase (BTK) inhibitor with high selectivity. The drug's safety profile in 2 pivotal 52-week REMIX-1 and REMIX-2 trials was also highlighted.

During the REMIX studies, the medication was provided to patients with CSU as an add-on therapy among individuals who remained symptomatic despite second-generation H1-antihistamines. Given BTK's notable role in B-cell activation and subsequent autoantibody production, Metz and coauthors' new analysis explored whether remibrutinib therapy alters one's autoantibody levels.

In this study, the team implemented a bead-based cytometric assay to measure IgG autoantibodies among 1,191 samples which they gathered at baseline, at the 24-week mark, and at the 52-week mark. These samples were collected from 397 REMIX trial participants with CSU. These study subjects were randomized to be treated with oral remibrutinib on a 25 mg, twice daily dose or a placebo up to Week 24. At this point, all patients involved in the analysis were given remibrutinib 25 mg twice-per-day through to Week 52.

Metz and colleagues also evaluated participants' levels of soluble CD23 (the low-affinity IgE receptor, FcεRII) via immunoassay. They also evaluated B-cell subset frequencies through flow cytometry at baseline, Week 4, Week 12, Week 24, and Week 52. Biomarker profiles were then integrated by the investigators with clinical data, treatment response, placebo response, and Chronic Urticaria Index (CUI) test results for their subgroup analyses.

Patients that tested positive at the point of baseline on the CUI (CUI+) were shown by the investigative team to have significantly raised levels of CSU-linked autoantibodies compared with CUI-negative (CUI–) subjects. These autoantibodies included anti-FcεRI, anti-TPO, and anti-TG. In their subgroup analyses, Metz et al concluded that remibrutinib treatment led to a significant dip in FcεRI- and TG-specific IgG autoantibodies at Week 24 in CUI+ patients, relative to those treated with placebo.

Additionally, the team found that participants initially on placebo who shifted to remibrutinib at the 24-week mark exhibited comparable reductions in specific IgG autoantibody levels by the 52-week mark. They also found levels of soluble CD23 were significantly increased among CUI+ patients at the point of baseline. This served as an indicator of enhanced B-cell activation. Any dips in autoantibody levels during remibrutinib treatments were accompanied by reductions in patients' circulating non-switched memory B cells and a significant drop in soluble CD23.

References

1. Metz M, Saini S, Haemmerle S, et al. Remibrutinib decreases specific IgG autoantibody levels in patients with Chronic Spontaneous Urticaria. Presented at the 2025 European Academy of Dermatology and Venereology (EADV) Congress, Sept 17-20, 2025.

2. Scarupa M. Remibrutinib for CSU Treatment. HCPLive. July 14, 2025. Accessed September 19, 2025. https://www.hcplive.com/view/remibrutinib-for-csu-treatment.