Remibrutinib reduces rescue medication use among adults with chronic spontaneous urticaria
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Remibrutinib reduced the need for rescue medication and improved symptoms among patients with chronic spontaneous urticaria, according to a study presented at the European Academy of Allergy and Clinical Immunology Hybrid Congress.
Also, remibrutinib (LOU064, Novartis) achieved these outcomes despite reduced use of second-generation H1 antihistamines (H1-AH), Marcus Maurer, MD, professor of dermatology and allergy and associate director of the Allergie-Centrum-Charité in Berlin, said in his presentation.
“Now we have another treatment option here, which I find very promising,” Maurer said.
H1-AH usually is recommended as first-line treatment for chronic spontaneous urticaria (CSU), the researchers reported. Remibrutinib, however, is a covalent oral inhibitor of Bruton’s tyrosine kinase (BTK), which is essential for activating mast cells and basophils.
According to the researchers, the drug is novel, highly selective and potent, making it a potentially attractive therapeutic target for CSU.
“If you block that BTK, the auto-antibody production in patients with spontaneous chronic urticaria is blocked,” Maurer said.
The multicenter, double-blind, phase 2b study involved 311 adults (71.4% women; median age, 45 years ± 14.9 years) with moderate to severe CSU that was uncontrolled with H1-AH treatment.
Patients were randomly assigned to receive remibrutinib in daily doses of 10 mg (n = 44), 35 mg (n = 44) or 100 mg (n = 47) or twice daily doses of 10 mg (n = 44), 25 mg (n = 44) or 100 mg (n = 45), with 43 receiving placebo.
These doses were prescribed in addition to background maintenance H1-AH at labeled dose and a different second-generation H1-AH as rescue medication as needed to treat unbearable symptoms during screening, treatment and follow-up periods.
Patients recorded the number of rescue H1-AH tablets they used during the previous 24 hours once each day on an eDiary device. The researchers calculated weekly use of rescue medication as the sum of the dose per day over 7 days.
Each of the remibrutinib groups experienced early reductions in weekly use of H1-AH rescue medications, which then remained low. Weekly mean ranges for doses totaled 2.8 to 8.2 for weeks 1 to 12, compared with 6.4 to 9.4 at baseline. The placebo group did not experience any reductions in rescue medication.
At week 12, the researchers found that the patients on remibrutinib used fewer rescue medication tablets each week, while the placebo group used more.
“Patients, when they are with noneffective treatment, use more rescue medication,” Maurer said. “That’s not what happens with remibrutinib.”
Specifically, among those receiving daily treatment, the 10 mg group used 5.8 tablets vs. 8.7 at baseline; the 35 mg group used 3.9 vs. 6.6; and the 100 mg group used 4 vs. 6.4. Among those receiving twice daily treatment, the 10 mg group used 5.1 tablets vs. 7.6 at baseline; the 25 mg group used 4.5 vs. 9; and the 100 mg group used 7.1 vs. 9.4. The placebo group used 11.9 tablets at week 12, compared with 9 at baseline.
“Patients recognize they don’t need rescue medication. They still improve markedly in their disease activity in the absence of additional rescue medications,” Maurer said.
The researchers further found that patients on remibrutinib experienced significant improvements in their 7-day Urticaria Activity Score at weeks 4 and 12 from baseline compared with placebo, in addition to rapid onset of action, a favorable safety profile and no dose-dependent pattern of adverse events, along with improvements in control and quality of life.
“My prediction is that once we have remibrutinib in our hands to help our patients, these patients will be just fine with remibrutinib monotherapy,” Maurer said.
Although the study period was 12 weeks, Maurer cautioned that real-world treatment will be longer.
“Follow the guideline. Treat the disease until it’s gone. This will not be a treatment that people should or will use for just 12 weeks or 16 weeks. This will be long-term treatment,” he said, adding that studies are underway examining the long-term safety and tolerability of BTK inhibition in patients with CSU. However, Maurer remains optimistic.
“The future of chronic spontaneous urticaria is bright,” he said.
Reference:
- Remibrutinib (LOU064) shown to reduce the use of rescue medication in patients with chronic spontaneous urticaria: Findings from a phase 2b study. https://eaaci-cdn-annual2022-media.azureedge.net/media-library-uploads/14_Remibrutinib_shown_to_reduce_the_use_of_rescue_medication_in_patients_with_chronic_spontaneous_urticaria_2_da10fded35.pdf. Published July 1, 2022. Accessed July 5, 2022.