WEDNESDAY, April 23, 2025 (HealthDay News) -- Rilzabrutinib, an oral reversible covalent Bruton tyrosine kinase inhibitor, is beneficial for treating patients with moderate-to-severe antihistamine-refractory chronic spontaneous urticaria (CSU), according to a study published online April 23 in JAMA Dermatology.

Ana Giménez-Arnau, M.D., Ph.D., from the Universitat Pompeu Fabra in Barcelona, Spain, and colleagues examined the efficacy and risk profile of rilzabrutinib for patients with CSU in a phase 2 randomized study, with a 12-week, double-blind, placebo-controlled period followed by a 40-week, open-label extension. Participants aged 18 to 80 years with moderate-to-severe CSU, not adequately controlled with H1-antihistamine treatment were randomly assigned to rilzabrutinib once, twice, or three times per day (400, 800, or 1,200 mg/day) or matching placebo in a 1:1:1:1 ratio.

The primary analysis population included 143 omalizumab-naive patients. The researchers observed significant reductions from baseline at week 12 in weekly Itch Severity Score (ISS7) and weekly Urticaria Activity Score (UAS7) with rilzabrutinib, 1,200 mg/day, versus placebo (least squares mean, −9.21 versus −5.77 and −16.89 versus −10.14, respectively). In addition, there were improvements in the weekly Hives Severity Score (HSS7) and weekly Angioedema Activity Score (AAS7). As early as week 1, improvements were seen in ISS7, UAS7, HSS7, and AAS7. At week 12, there was improvement noted in CSU-related biomarkers, including soluble Mas-related G protein-coupled receptor X2, compared with placebo. A favorable risk-benefit profile was seen for rilzabrutinib.

"Collectively, these findings offer initial evidence that the mechanism of action of rilzabrutinib may be effective in endotypes that are recalcitrant to available treatment," the authors write.

Several authors disclosed ties to biopharmaceutical companies, including Sanofi, which manufactures rilzabrutinib and funded the study.

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