No clinically meaningful impact of remibrutinib on mean immunoglobulin levels or infections in chronic spontaneous urticaria

Abstract

Prérequis/contexte

Remibrutinib is an oral, highly selective Bruton's tyrosine kinase (BTK) inhibitor.

Objectifs

As BTK plays an important role in immune responses, we analyze the impact of remibrutinib on mean total immunoglobulin levels and infection rates in patients with Chronic Spontaneous Urticaria (CSU) in the phase 3 REMIX-1 and REMIX-2 studies.

Méthodes

REMIX-1/-2 are multicenter, randomized, double-blind, placebo-controlled studies assessing the efficacy and safety of remibrutinib in patients with CSU inadequately controlled by H1-antihistamines. Patients were randomized 2: 1 to remibrutinib 25 mg twice daily or placebo (24 weeks), followed by open-label remibrutinib (28 weeks). We present a pooled data analysis for mean serum immunoglobulin levels (IgA, IgE, IgG, IgM) assessed at baseline, weeks 12, 24, and 52, and exposure-adjusted occurrence rate (EAOR) of infection treatment-emergent adverse events (TEAEs) per 100 patient-years.

Résultats/discussions

The safety analysis included 606 and 306 patients in the remibrutinib and placebo groups, respectively. Mean total immunoglobulin levels remained similar over time and between arms. For remibrutinib, mean immunoglobulin levels at baseline and week 52, respectively, were: IgA, 2.2 g/L and 2.3 g/L; IgE, 528.0 μg/L and 535.0 μg/L; IgG, 11.3 g/L and 10.9 g/L; IgM, 1.1 g/L and 0.8 g/L. Up to week 24, ≥1 infection-related TEAE occurred in 33.5% (remibrutinib) and 34.3% (placebo) of patients. The EAOR of infection-related TEAEs was 111.7 (remibrutinib) versus 114.7 (placebo) through week 24, and 89.5 (remibrutinib) through week 52.

Conclusion

Remibrutinib did not have a clinically meaningful impact on mean total immunoglobulin levels over time. Infection rates were comparable between remibrutinib and placebo and did not increase with long-term treatment.