Chronic spontaneous urticaria impacts roughly 1.7 million people in the United States, underscoring the need for improved therapies. Data presented at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting demonstrated that once-daily 75 mg povorcitinib produced greater reductions in weekly urticaria activity scores over 12 weeks than placebo.
Mechanism of Action
Povorcitinib is a once-daily, selective oral JAK1 inhibitor with high-volume distribution, allowing it to efficiently reach and maintain therapeutic levels in skin tissue. It is currently being investigated as a treatment option for CSU, a condition characterized by unpredictable hives that can significantly disrupt daily life.
The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway plays a role in CSU pathogenesis. In this phase 2 randomized, double-blind study, Jonathan A. Bernstein, MD, FACAAI, FAAAAI, FACP, adjunct professor of internal medicine at the University of Cincinnati College of Medicine, and colleagues, examined the efficacy and safety of three povorcitinib doses in 136 adults with moderate-to-severe CSU inadequately controlled by second-generation H1 antihistamines.
Key Takeaways
- Researchers evaluated three povorcitinib doses for CSU.
- The 75 mg group produced the greatest improvement in weekly urticaria activity scores at week 12 vs. placebo.
- All doses were well tolerated.
Of the 136 participants, 34 received placebo, while 33, 34, and 35 received 15 mg, 45 mg, and 75 mg povorcitinib, respectively. Patients had CSU for at least 3 months and had a UAS7 score of at least 16 in the week before randomization. All groups received standard-of-care therapy with their treatment.
Positive Findings
A total of 116 patients completed the 12-week trial. The 75 mg group demonstrated the greatest least-squares mean reduction in UAS7 score compared with placebo. This group also had the highest proportion of patients achieving disease control (UAS7 ≤ 6) and the highest proportion achieving complete symptom resolution (UAS7 = 0) by week 12.
Impact on Quality of Life
CSU symptoms, which can include hives that come and go, typically lasting between 30 minutes and 24 hours, as well as swelling and a tingling sensation, can significantly impair quality of life. Patients in the 75 mg group demonstrated particularly notable improvements, separating from placebo in daily hives severity (–0.6 vs. –0.4) and in daily itch severity (–0.7 vs. –0.3).
Improvements were also reflected in Dermatology Life Quality Index (DLQI) scores. The 75 mg dose produced the greatest improvement compared with placebo (–13.4 vs. –9.5), indicating meaningful benefits for daily functioning and comfort.
Looking Ahead
Povorcitinib 75 mg demonstrated rapid symptom improvement as early as day 3 and enabled more patients to achieve complete disease control by week 12. With its favorable safety and tolerability profile, povorcitinib 75 mg may represent a promising future treatment option for patients with CSU.
