Treating Chronic Spontaneous Urticaria by Blocking Histamine Release with Remibrutinib
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on April 14th, 2025
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Chronic spontaneous urticaria is an allergic condition marked by unpredictable itching and hives, with no identifiable trigger. This allergic reaction results from mast cell degranulation. While second-generation H1 antihistamines are the most commonly prescribed treatment, up to 75% of patients may not respond even at maximum doses. Novartis sponsored a study to evaluate the effectiveness of remibrutinib, a BTK inhibitor, in managing urticaria.
The phase 2 clinical trial enrolled 925 patients who had been diagnosed with chronic spontaneous urticaria for over 6 months and had not responded to treatment with second-generation H1 antihistamines. Disease severity was measured using the 7-day Urticaria Activity Score (UAS7), which ranges from 0 to 42, with 42 representing the most severe symptoms. Baseline assessments showed an average UAS7 score of approximately 30.
Participants were randomly assigned to receive either a placebo or 25 mg of remibrutinib, taken orally twice daily. Remibrutinib is a biologic that specifically binds to and inhibits Bruton’s tyrosine kinase (BTK) within the cell cytoplasm. BTK acts as a signal transducer, triggering the release of histamine when IgE binds to FcεRI receptors on mast cells and basophils.
After 12 weeks of treatment, researchers observed that remibrutinib reduced urticaria severity by approximately 20%, as measured by the UAS7 score. Follow-up assessments until week 24 revealed that this therapeutic effect was sustained after treatment cessation, though the authors did not offer an explanation for the prolonged activity. The investigators concluded that these promising results warrant a larger phase 3 trial to further explore the efficacy and safety profile of remibrutinib. In the phase 2 trial, there was no significant difference in the incidence of adverse events between the remibrutinib and placebo groups, with all recorded events being mild; however, petechiae was more frequently reported in the remibrutinib group.
The phase 2 clinical trial enrolled 925 patients who had been diagnosed with chronic spontaneous urticaria for over 6 months and had not responded to treatment with second-generation H1 antihistamines. Disease severity was measured using the 7-day Urticaria Activity Score (UAS7), which ranges from 0 to 42, with 42 representing the most severe symptoms. Baseline assessments showed an average UAS7 score of approximately 30.
Participants were randomly assigned to receive either a placebo or 25 mg of remibrutinib, taken orally twice daily. Remibrutinib is a biologic that specifically binds to and inhibits Bruton’s tyrosine kinase (BTK) within the cell cytoplasm. BTK acts as a signal transducer, triggering the release of histamine when IgE binds to FcεRI receptors on mast cells and basophils.
After 12 weeks of treatment, researchers observed that remibrutinib reduced urticaria severity by approximately 20%, as measured by the UAS7 score. Follow-up assessments until week 24 revealed that this therapeutic effect was sustained after treatment cessation, though the authors did not offer an explanation for the prolonged activity. The investigators concluded that these promising results warrant a larger phase 3 trial to further explore the efficacy and safety profile of remibrutinib. In the phase 2 trial, there was no significant difference in the incidence of adverse events between the remibrutinib and placebo groups, with all recorded events being mild; however, petechiae was more frequently reported in the remibrutinib group.