Targeting B-cells in Hidradenitis Suppurativa: A Systematic Review of Bruton's Tyrosine Kinase Inhibition as a Target

Document Type

Conference Proceeding

Publication Date

11-10-2025

Publication Title

J Invest Dermatol

Keywords

tyrosine kinase inhibitors, hidradenitis suppurativa, B-cell signaling, Bruton’s tyrosine kinase

Abstract

Hidradenitis suppurativa (HS) is a debilitating skin condition characterized by recurrent abscesses, nodules, and sinus tracts in the axillary, inguinal, and anogenital areas. Adequate control of disease activity is essential in reducing psychosocial burden and improving quality of life. Adalimumab and secukinumab remain the only FDA approved biologic, but many patients experience suboptimal control. Bruton's tyrosine kinase inhibitors (BTKi), originally developed for hematologic malignancies, are emerging as potential therapies in immune-mediated skin conditions. A systematic review was conducted to evaluate BTKi as a novel therapy for hidradenitis suppurativa using PubMed. Articles were included if available in English, published in the last 25 years, and evaluated tyrosine kinase inhibitors in the treatment of hidradenitis suppurativa. Reviews and meta-analyses were excluded. Sixteen studies were screened, and two studies were included due to limited published articles available on tyrosine kinase inhibitors to treat HS. No published clinical trials directly assessing BTKi in HS were identified. Preclinical transcriptomic and proteomic analyses highlight B-cell signaling as a therapeutic target, with the BTK pathway localized to CD3+ and CD138+ B-cells. While no published BTKi studies in HS exist, a small proof-of-concept trial of the spleen tyrosine kinase inhibitor fostamatinib reported Hidradenitis Suppurativa Clinical Response score (HiSCR) achievement in 85% of participants by week 4. These findings suggest that modulation of B-cell–related pathways attenuate proinflammatory activity in HS. Published evidence for BTKi in HS is currently limited to mechanistic rationale and indirect data from related tyrosine kinase inhibitors. Phase 3 clinical trials in pemphigus vulgaris successfully showed a reduction in corticosteroid use when treated with BTKi. Further early-phase clinical trials are warranted to establish safety, efficacy, and durability of BTK inhibition in HS. This review underscores an urgent need to expand therapeutic options for patients with refractory disease.

Volume

145

Issue

11

First Page

1

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