The Bruton’s Tyrosine Kinase Inhibitor Remibrutinib Exhibits No Impact on Serum Immunoglobulin Levels: Insights from Chronic Spontaneous Urticaria (P10-6.018)

https://www.neurology.org/doi/abs/10.1212/WNL.0000000000206293

Neurology, April 9, 2024 issue 102 (17_supplement_1). https://doi.org/10.1212/WNL.0000000000206293

Robert Bermel, Warner Carr, Tanuja Chitnis, Thomas Dörner, Koremasa Hayama, Michihiro Hide, Marcus Maurer, Xavier Montalban, Gordon Sussman, Heinz Wiendl, Swapnil Dahale, Virginia DeLasHeras, Sibylle Haemmerle, Bernd Kieseier, Karine Lheritier, Artem Zharkov, Roman Willi, and Ana Giménez-Arnau

Abstract

Objective:

To assess serum immunoglobulin (Ig) levels over time in a Phase 2b core (NCT03926611) and extension (NCT04109313) study of remibrutinib in patients with chronic spontaneous urticaria (CSU), receiving various doses including 100mg b.i.d., the dosing regimen being evaluated in the Phase 3 REMODEL trials (NCT05147220, NCT05156281) in relapsing multiple sclerosis (MS).

Background:

Remibrutinib is a highly selective, potent, covalent, oral Bruton’s tyrosine kinase inhibitor (BTKi) that downregulates B cell as well as myeloid cell activation without cellular depletion. Here, we report on serum immunoglobulin levels in CSU patients exposed to remibrutinib up to 100mg b.i.d. for up to 52 weeks.

Design/Methods:

Patients were randomized to receive various doses of remibrutinib (10–100 mg q.d./b.i.d.) or placebo for up to 12 weeks (core study). Eligible patients entered a 52-week open-label extension study with remibrutinib 100 mg b.i.d. Total serum levels of different immunoglobulins were assessed at baseline, Week 12 (end of core) and Week 52 (end of extension).

Results:

Of the 309 patients included in the analysis, 194 patients rolled-over to the 52-week extension. No relevant changes in the total serum immunoglobulin levels up to Week 12 and Week 52 were observed. In the 194 patients receiving remibrutinib 100mg b.i.d. in the extension study (mean age: 45.5 years; % female: 71.6), mean baseline and Week 52 IgG levels (μg/mL) were 11.0±2.43 and 10.5±2.49, respectively, and the corresponding mean IgM levels were 1.1±0.83 and 0.9±0.74.

Conclusions:

Remibrutinib treatment did not affect total Ig levels in participants with CSU in phase 2 studies, including with long-term treatment up to 52 weeks with 100mg b.i.d., the dose used in MS clinical trials.

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