Document Type
Article
Publication Title
Nature Medicine
ISSN
1078-8956
Volume
27
DOI
10.1038/s41591-021-01537-w
First Page
1961
Last Page
1969
Publication Date
11-8-2021
Abstract
Bruton’s tyrosine kinase (BTK) is crucial for FcεRI-mediated mast cell activation and essential for autoantibody production by B cells in chronic spontaneous urticaria (CSU). Fenebrutinib, an orally administered, potent, highly selective, reversible BTK inhibitor, may be effective in CSU. This double-blind, placebo-controlled, phase 2 trial (EudraCT ID 2016-004624-35) randomized 93 adults with antihistamine-refractory CSU to 50 mg daily, 150 mg daily and 200 mg twice daily of fenebrutinib or placebo for 8 weeks. The primary end point was change from baseline in urticaria activity score over 7 d (UAS7) at week 8. Secondary end points were the change from baseline in UAS7 at week 4 and the proportion of patients well-controlled (UAS7 ≤ 6) at week 8. Fenebrutinib efficacy in patients with type IIb autoimmunity and effects on IgG-anti-FcεRI were exploratory end points. Safety was also evaluated. The primary end point was met, with dose-dependent improvements in UAS7 at week 8 occurring at 200 mg twice daily and 150 mg daily, but not at 50 mg daily of fenebrutinib versus placebo. Asymptomatic, reversible grade 2 and 3 liver transaminase elevations occurred in the fenebrutinib 150 mg daily and 200 mg twice daily groups (2 patients each). Fenebrutinib diminished disease activity in patients with antihistamine-refractory CSU, including more patients with refractory type IIb autoimmunity. These results support the potential use of BTK inhibition in antihistamine-refractory CSU.
Recommended Citation
Metz, M.,
Sussman, G.,
Gagnon, R.,
Staubach, P.,
Tanus, T.,
Yang, W. H.,
Lim, J. J.,
Clarke, H. J.,
Galanter, J.,
Chinn, L. W.,
Chu, T.,
Teterina, A.,
Burgess, T.,
Haddon, D. J.,
Lu, T. T.,
&
Maurer, M.
(2021).
Fenebrutinib in H1 antihistamine-refractory chronic spontaneous urticaria: a randomized phase 2 trial.
Nature Medicine, 27, 1961–1969.
DOI: 10.1038/s41591-021-01537-w
https://scholarlycommons.pacific.edu/phs-facarticles/635
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