Long-term treatment with remibrutinib shows favorable safety and tolerability and demonstrated robust clinical efficacy in patients with chronic spontaneous urticaria, according to the results of a phase 2b trial.
Chronic spontaneous urticaria (CSU) is a condition in which wheals (hives) and/or angioedema occur persistently for longer than 6 weeks, greatly affecting the quality of life for patients. The global prevalence of CSU ranges from 0.5% to 1.5% and has been increasing in recent years.
Remibrutinib is a highly selective inhibitor of Bruton tyrosine kinase, taken orally. It has shown promising results in rapidly controlling the disease in CSU patients who continue to experience symptoms despite treatment with second-generation H1 antihistamines.
A phase 2b extension study, published in the Journal of Allergy and Clinical Immunology, discusses the long-term safety, tolerability, and efficacy of remibrutinib in patients with CSU.
Baseline Characteristics
The study enrolled 194 patients, with an average age of 45.5 years. The majority of patients (71.6%) were female. The mean BMI was 28.1 kg/m², and the average duration of chronic spontaneous urticaria (CSU) was 5.8 years. Most patients had moderate to severe CSU, with a mean baseline Urticaria Activity Score over 7 days (UAS7) of 27.9. Moreover, 27.8% of patients had prior exposure to anti-IgE therapy.
Remibrutinib Is Safe and Well-Tolerated
Overall, 71.6% (139/194) of patients reported at least one treatment-emergent adverse event (TEAE), with most being mild-to-moderate in severity. Severe events were reported in 4.1% of patients, with infections being the most common TEAEs, followed by skin disorders and gastrointestinal issues. The most frequently reported adverse events included CSU, COVID-19, headache, and eczema. Serious adverse events (SAEs) were uncommon (3.1% of patients), and none were considered to be related to the study drug. No deaths were reported during the study period.
Laboratory and Vital Signs Analysis
Analysis of vital signs, laboratory parameters, and electrocardiograms revealed no significant findings. Liver enzyme abnormalities were rare and transient, with no notable trends compared to baseline.
Immunoglobulin Level Changes
Treatment with remibrutinib led to decreases in mean IgE levels compared to baseline, with no significant changes in IgA levels observed. Decreases were also noted in IgG and IgM levels over time. At week 52, the mean IgE levels decreased by 140.22 μg/L from a baseline of 839.47 μg/L.
Rapid and Sustained Symptom Improvement
Treatment with remibrutinib consistently improved the signs and symptoms of CSU over time. At week 4, the mean change from baseline in UAS7 was −17.6. Clinical improvement was rapid, with UAS7 decreases from baseline at week 1 (−14.8) and continuing until week 52. Mean change from baseline in UAS7 was 219.4 and 221.8 at weeks 12 and 52, respectively.
High Rates of Complete and Well-Controlled Disease Response
A complete response (UAS7=0) was achieved in 27.3% of patients at week 4 using nonresponder imputation. The percentage of patients with a UAS7=0 response increased to 28.2% at week 4, 43.4% at week 12, and 55.8% at week 52. Additionally, a well-controlled disease response (UAS7 <6) was observed in 51.0% of patients at week 4, 56.6% at week 12, and 68.0% at week 52.
Source:
Jain, V., Giménez‐Arnau, A., Hayama, K., Reich, A., Carr, W., Tillinghast, J., Dahale, S., Lheritier, K., Walsh, P., Zharkov, A., Hugot, S., & Haemmerle, S. (2023). Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2023.10.007
