Chronic spontaneous urticaria shows clinically meaningful improvement with remibrutinib

11th August 2023

The use of remibrutinib leads to rapid, clinically meaningful improvements across urticaria disease activity scores in patients with chronic spontaneous urticaria (CSU), according to the top-line results of two trials by the manufacturer Novartis.

The identically designed phase III trials REMIX-1 and REMIX-2 were undertaken in adult patients (≥ 18 years) who had experienced CSU for six months or longer and who found the condition to be inadequately controlled by second-generation H1-antihistamines.

The primary endpoints include absolute change from baseline in the weekly urticaria activity score, absolute change in itch severity score and hive severity score at Week 12.

Remibrutinib was found to have a fast onset of action, with patients seeing an improvement as early as two weeks after treatment initiation.

Patients currently enrolled in REMIX-1 and REMIX-2 will continue to receive treatment up to Week 52, and will have the opportunity to continue in a long-term extension trial.

Shreeram Aradhye, president, global drug development and chief medical officer at Novartis, said: ‘CSU is a distressing and unpredictable disease, and patients urgently need effective, convenient and well-tolerated treatments that can provide rapid and sustained relief from the relentless itching and deep tissue swelling that greatly impact their daily lives.

‘These positive top-line results from the Phase III REMIX studies confirm that remibrutinib, a highly selective BTK inhibitor, has the potential to be a first-in-class, oral treatment for people living with CSU whose symptoms are refractory despite use of antihistamines.‘

CSU and remibrutinib

CSU affects approximately 40 million people worldwide and is characterised by the sudden appearance of pruritic wheals and/or angioedema, persisting for more than six weeks. In addition, CSU causes significant emotional distress, with the majority of patients suffering from sleep deprivation and high rates of mental disorders, such as anxiety or depression.

There are limited effective treatments available for CSU, although recently it was found that the monoclonal antibody dupilumab is effective when used in conjunction with antihistamines.

Remibrutinib is a highly selective, oral Bruton’s tyrosine kinase (BTK) inhibitor that blocks the BTK cascade and prevents the release of histamine that causes itch, hives/welts and swelling. In Phase II studies, remibrutinib demonstrated fast onset of action and sustained efficacy in patients with moderate to severe CSU. The drug has been shown to be well-tolerated across all doses studied in Phase II.

Dupilumab treatment improves spontaneous chronic urticaria activity and quality of life

2nd March 2023

Dupilumab treatment in patients with chronic spontaneous urticaria for 24 weeks improves urticaria activity and quality of life

In an abstract presented at the American Academy of Allergy Asthma and Immunology (AAAAI) 2023 in San Antonio, US and published as a supplement in the Journal of Clinical Allergy and Immunology, dupilumab treatment for 24 weeks, in patients with chronic spontaneous urticaria, already taking H1-antihistamines, led to significant reductions in urticarial activity and improvements in quality of life.

Chronic spontaneous urticaria is an endogenous disorder that is strongly associated with autoimmunity, particularly with immunoglobulin G antibody to the alpha subunit of the IgE receptor. The term ‘chronic urticaria’ relates to urticaria lasting for more than six weeks and has two forms: chronic inducible urticaria and chronic spontaneous urticaria, with the latter giving rise to symptoms independent of an exogenous stimulus. Treatment guidelines published in 2022 recommend the use of second-generation H1-anti-histamines, at a dose of up to four times the usual dose. However, in 2019, a case report described use of dupilumab treatment at an initial dose of 600 mg then 300 mg every two weeks in a patient with therapy resistant chronic spontaneous urticaria. Within three months, the patient’s urticaria duration and severity resolved. Furthermore, in 2022, a randomised, placebo-controlled, phase 3 trial, of dupilumab treatment as an ‘add-on’ to therapy with either standard of < 4-fold antihistamine dosing or matching placebo, showed that after 24 weeks, the least squares mean change in the itch severity score over 7 days and the urticaria activity score over 7 days (UAS7) were both significantly reduced in those given dupilumab treatment.

Dupilumab treatment and urticarial activity

Data presented at the AAAI conference relates to the impact of dupilumab on urticarial activity score over 7 days (UAS7) and quality of life based on the dermatology quality of life index (DLQI). Patients taking an H1-antihistamine (up to fourfold approved dose) were randomised to add-on dupilumab 300 mg (or 200 mg for body weights < 60 kg but > 30 kg) or matching placebo every 2 weeks for 24 weeks.

The results showed that dupilumab treatment produced a significant improvement in the UAS7 score at week 24 (p = 0.0003) as well an improvement in the DLQI (p = 0.0026) compared to placebo.

Citation
Maurer M et al. Dupilumab Improves Urticaria Activity And Quality Of Life In Patients With Chronic Spontaneous Urticaria (CSU). J Allergy Clin Immunol 2023