In the phase 2b ARROYO trial, although blood eosinophils were almost completely depleted, benralizumab treatment did not show any therapeutic advantage compared to a placebo for the treatment of chronic spontaneous urticaria.
Chronic spontaneous urticaria (CSU) involves a complex interplay of various cell types and molecular mechanisms, with mast cells traditionally considered the primary drivers. However, eosinophils and other cells also contribute significantly to the disease process. CSU can be categorized into two main endotypes: type I, associated with immunoglobulin E (IgE) antibodies against autoantigens, and type IIb, driven by autoantibodies that activate mast cells. Upon IgE stimulation, mast cells release histamine, contributing to the characteristic symptoms.
Benralizumab, a humanized anti-IL-5 receptor alpha monoclonal antibody, effectively depletes eosinophils and reduces basophil counts via enhanced antibody-dependent cell-mediated cytotoxicity. This 24-week multinational, randomized, double-blind, placebo-controlled, phase 2b clinical trial evaluated the therapeutic effectiveness and safety of benralizumab in patients with CSU who exhibited symptoms despite receiving H1 antihistamine therapy. The study’s results were published in the British Journal of Dermatology.
Baseline Characteristics
The mean ages were 46.8 ± 14.4 years for benralizumab 30 mg, 45.6 ±15.1 years for benralizumab 60 mg, and 47.1 ± 14.3 years for placebo. Patients were primarily female and White. Baseline mean (SD) itch severity score over 7 days (ISS7) was similar across treatment groups. Of the 155 randomized and treated patients, 59 were randomly assigned to benralizumab 30 mg, 56 to benralizumab 60 mg, and 40 to placebo.
Clinical Outcomes of Benralizumab vs. Placebo in Chronic Urticaria
The change from baseline in ISS7 at Week 12 did not show any significant difference between benralizumab (both dosages) and placebo. The secondary endpoint of change from baseline in UAS7 score at Week 12 did not show any significant difference between benralizumab (both dosages) and placebo. The proportion of respondents with UAS7 ≦6 or UAS7 = 0 did not differ between Weeks 12 and 24. There were no significant variations in UAS7 severity scores between the groups.
No Significant Changes in Hives Severity Score
During Weeks 12 and 24, there were no statistically significant changes observed from the initial hives severity score over 7 days (HSS7). Comparing benralizumab doses of 30 mg and 60 mg to placebo, the differences were not statistically significant at both Week 12 and Week 24. Similarly, when compared with placebo, benralizumab did not show any significant differences in efficacy outcomes for all other secondary endpoints during the placebo-controlled period.
Eosinophil Depletion and Treatment Consistency
Benralizumab treatment resulted in marked depletion of blood eosinophils, consistent with its known pharmacodynamic effects. Serum concentrations of benralizumab were higher in the 60 mg group compared to the 30 mg group at Week 12, but became similar by Week 24. A subset of patients developed anti-drug antibodies (ADA), but this did not affect eosinophil depletion. Rescue medication use decreased over time, with similar rates observed across all treatment arms.
Benralizumab Safety Profile and Adverse Event Analysis
Safety profiles were consistent with previous findings, with no new safety concerns identified, even at higher dosages. The most common adverse events were COVID-19, headache, and myalgia, with the most serious adverse events resolved and unrelated to benralizumab. Subgroup analyses based on disease characteristics and baseline biomarkers did not reveal any evidence of differential a response to benralizumab.
Source:
Altrichter, S., Giménez-Arnau, A. M., Bernstein, J. A., Metz, M., Bahadori, L., Bergquist, M., Brooks, L., Ho, C. N., Jain, P., Lukka, P. B., Rodriguez-Suárez, E., Walton, C., Datto, C. J., & Investigators, t. A. S. (2024). Benralizumab does not elicit therapeutic effect in patients with chronic spontaneous urticaria: results from the phase 2b multinational, randomised, double-blind, placebo-controlled ARROYO trial. British Journal of Dermatology. https://doi.org/10.1093/bjd/ljae067
