TOPLINE:
Rilzabrutinib, an oral inhibitor of Bruton tyrosine kinase (BTK), demonstrated a rapid and substantial alleviation of symptoms in patients with chronic spontaneous urticaria (CSU) unresponsive to antihistamines at a dosage of 1200 mg/d compared with placebo.
METHODOLOGY:
- Researchers conducted a 52-week phase 2 trial comprising a 12-week double-blind, placebo-controlled period followed by a 40-week open-label extension across 51 centers in 12 countries in Asia, Europe, North America, and South America.
- A total of 160 participants with moderate to severe CSU (weekly Urticaria Activity Score [UAS7] ≥ 16; weekly Itch Severity Score [ISS7] ≥ 8) who were not adequately controlled with H1 antihistamine treatment were randomly assigned to receive rilzabrutinib at doses of 400 mg daily, 800 mg daily, 1200 mg daily, or placebo for 12 weeks.
- For the United States and US reference countries, the primary and secondary endpoints were the change from baseline at week 12 in ISS7 and UAS7, respectively.
- For non–US reference countries, the change from baseline in UAS7 was the primary outcome, while ISS7 served as the secondary endpoint.
TAKEAWAY:
- Rilzabrutinib, 1200 mg daily, significantly reduced UAS7 scores (least squares [LS] mean difference, −6.75 points; P = .02) and ISS7 scores (LS mean difference, −3.44 points; P = .02) compared with placebo at week 12.
- Improvements in symptoms were observed as early as week 1, with an LS mean difference for ISS7 of −4.21 (95% CI, −6.89 to −1.52) and UAS7 of −7.89 (95% CI, −12.98 to −2.81).
- Researchers noted improvement in weekly hive severity scores (LS mean difference, −3.24; P = .03). A higher proportion of patients treated with rilzabrutinib, 1200 mg/d, achieved well-controlled disease (UAS7 ≤ 6) than those receiving placebo (34.3% vs 11.1%).
- Rilzabrutinib demonstrated a favorable risk-benefit profile, with no new safety concerns. Diarrhea and nausea were the most common adverse events.
IN PRACTICE:
“The results of this randomized clinical trial demonstrated that rilzabrutinib may be an effective BTKI [BTK inhibitor] with a favorable risk-benefit profile for the treatment of H1 antihistamine-refractory patients with CSU,” authors of the study wrote. More research is needed to “determine long-term efficacy and potential harms,” they added.
SOURCE:
The study was led by Ana Giménez-Arnau, MD, PhD, Hospital del Mar Medical Research Institute, Universitat Pompeu Fabra, Barcelona, Spain, and was published online on April 23 in JAMA Dermatology.
LIMITATIONS:
The study had a small sample size, limited racial diversity, a low number of omalizumab-incomplete responders, and a short duration of follow-up.
DISCLOSURES:
This work was supported by Sanofi. Giménez-Arnau reported receiving grants and personal fees from various companies, including Novartis, and serving as principal investigator for clinical trials sponsored by AstraZeneca, Celldex Therapeutics, Escient Pharmaceuticals, and LEO Pharma. Other authors reported holding stocks in Sanofi and having a pending patent for a method of CSU treatment.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.