Benralizumab fails to beat placebo in chronic spontaneous urticaria

Key takeaways:

• Benralizumab treatment showed near complete depletion of blood eosinophils in chronic spontaneous urticaria.
• Despite this pharmacodynamic effect, there were no significant clinical improvements.

Despite blood eosinophils depletion, benralizumab did not show a clinical benefit over placebo in chronic spontaneous urticaria, according to a phase 2b trial.

“Chronic spontaneous urticaria (CSU) is a debilitating autoimmune skin disease that affects up to 1% of the global population,” Sabine Altrichter, MD, of the department of dermatology and venereology at Johannes Kepler University Hospital in Linz, Austria, and colleagues wrote. “The pathophysiology of CSU is complex, and the interplay of various cell types and molecular mechanisms defines the immune response of CSU.”

The randomized, double-blind, placebo-controlled, phase 2b ARROYO trial randomly assigned 155 patients with CSU to receive benralizumab 30 mg (n = 59), benralizumab 60 mg (n = 56) or placebo (n = 40) for 24 weeks. Of these, 50 (84.7%), 53 (96.4%) and 37 (92.5%), respectively, completed the 24-week trial period and entered a 28-week extension period.

The primary endpoint was a change at day 12 from baseline in itch severity score over 7 days (ISS7), and the key secondary endpoint was a change in urticaria activity score of 7 days (UAS7) at the same time point.

In patients who were treated with benralizumab there was a depletion of blood eosinophils at weeks 12 and 24; however, this change did not correlate with clinical results.

At week 12 there were no significant differences in ISS7 or UAS7 between either treatment group vs. placebo. The hives severity score over 7 days also did not have a statistically significant change in treatment groups compared with those in the placebo group at weeks 12 and 24.

“It was thought that direct targeting of the [interleukin]-5 receptor may be effective in CSU through its effects on immune-mediating cells, such as eosinophils,” the authors wrote. “However, in the 24-week placebo-controlled period of the ARROYO study, changes compared with placebo in the primary and key secondary endpoints were not observed in the overall population though benralizumab treatment did result in the expected pharmacodynamic effect of blood eosinophil depletion.”