New urticaria treatment works within a week

The BTK inhibitor is currently pending TGA approval, but phase 3 trials show fast and sustained symptom improvement where standard treatment has failed.

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Remibrutinib has been found to significantly reduce the severity of chronic spontaneous urticaria (CSU) in patients for which standard treatment had failed.

Significant symptom relief was reported as early as one week from initiation and continued to improve up to 52 weeks.

Nearly 1000 people were included in the REMIX-1 and REMIX-2 trials, two randomised double-blind placebo-controlled studies of oral remibrutinab, a highly selective Bruton’s tyrosine kinase (BTK) inhibitor.

Patients were randomized 2:1 to receive 25mg remibrutinib twice a day or placebo during the first 24 weeks, followed by a 28-week open-label treatment period.

Around 60% of participants randomised to remibrutinib across the studies had severe CSU at baseline, with a mean Urticaria Activity Score (UAS7) of 30.

After one week in both trials, the treatment group reported a roughly 12-point reduction in UAS7, compared to placebo with a 3-point reduction.

By 12 weeks, the scores had reduced for treatment and placebo group by 21 and 13 points respectively and at 24 weeks, 22 points and 15 points respectively.

At 52 weeks, UAS7 score reductions for both the original remibrutinab group and the placebo group who had transitioned to remibrutinab at week 24 were similar at around 23 points.

The improvements were observed in the placebo group as quickly as one week after transitioning to remibrutinab.

More than 60% of patients achieved well-controlled disease, including those who had transitioned for the open-label period, with a UAS7 score of six or less after 52 weeks.

After the double-blind portion of the trial, 40% of patients on remibrutinib reported a complete response with a UAS7 score of 0, which increased to 45% after the open-label treatment period.

Participants at baseline had a UAS7 score of at least 16 and an Itch Severity Score and Hives Severity Score of six or higher. All had used first-line antihistamines for at least six months without adequate effect.

They maintained their antihistamine regimen as concurrent background therapy and were allowed rescue medication antihistamine (up to four times the regular dose) for managing flare-ups throughout the study.

Biologics such as omalizumab, the standard second-line treatment, were prohibited throughout the study and for four months prior. Across both studies, around 30% of patients had prior exposure to anti-IgE biologics.

International guidelines for CSU management recommend H1-antihistamines as first-line treatment, but researchers said that more than 50% of patients continue to experience symptoms which impact their quality of life.

When patients are unresponsive, off-label updosing to up to four times the usual dose is recommended. According to the study, up to 75% of patients who do this experience no or only partial symptom relief.

Omalizumab is the second-line treatment, but studies show only a third of eligible patients are escalated to this treatment option. Of those who do initiate the therapy, around 30% remain symptomatic.

Patients not showing benefit with omalizumab can then be treated with off-label cyclosporine, but this is associated with a high incidence of adverse events.

All adverse events in the trials were comparable between the treatment and placebo groups. All serious adverse events were found to be unrelated to the treatment, and no deaths occurred.

Less than 5% of participants in the remibrutinib group discontinued treatment due to adverse events in the first 24 weeks, with similar rates for patients who transitioned from placebo to remibrutinib.

After adjusting for treatment duration, the overall frequency of adverse events decreased over long-term exposure.

Only 1% of those taking remibrutinib across the studies discontinued use due to lack of efficacy.

Novartis applied for TGA approval of remibrutinib for CSU in June this year, and the FDA approved it last month.

The Journal of Allergy and Clinical Immunology, 18 October 2025