The Bruton’s Tyrosine Kinase Inhibitor Remibrutinib Exhibits No Impact on Serum Immunoglobulin Levels: Insights from Chronic Spontaneous Urticaria
Robert Bermel1, Warner Carr2, Tanuja Chitnis3, Thomas Dörner4, Koremasa Hayama5, Michihiro Hide6, Marcus Maurer7, Xavier Montalban8, Gordon Sussman9, Heinz Wiendl10, Swapnil Dahale11, Virginia DeLasHeras12, Sibylle Haemmerle12, Bernd Kieseier13, Karine Lheritier13, Artem Zharkov13, Roman Willi13, Ana Giménez-Arnau14
1Cleveland Clinic, 2Allergy and Asthma Associates of Southern California, and Southern California Research, 3Brigham and Women's Hospital, 4Department of Rheumatology and Clinical Immunology, Charite Universitätsmedizin Berlin, 5Nihon University School of Medicine, 6Hiroshima Citizens Hospital, 7Charité - Universitätsmedizin Berlin, 8Vall Hebron University Hospital-Multiple Sclerosis Centre of Catalonia, 9Gordon Sussman Clinical Research Inc., 10University of Muenster, 11IQVIA, 12Novartis Pharma AG, 13Novartis, 14Hospital del Mar - IMIM, Universitat Pompeu Fabra
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.