Subcutaneous ligelizumab therapy of 72 mg or 240 mg every 4 weeks is associated with greater control of chronic spontaneous urticaria symptoms, including hives and itch, compared with omalizumab, study data in the New England Journal of Medicine suggest.
In this multicenter, phase 2b dose-finding trial, patients with chronic spontaneous urticaria and a mean weekly urticaria activity score of ≥12 were randomly assigned to either ligelizumab 24 mg (n=43), ligelizumab 72 mg (n=84), ligelizumab 240 mg (n=85), omalizumab 300 mg (n=85), or placebo (n=43). Treatments were administered subcutaneously every 4 weeks for a total of 20 weeks. Another group was randomly assigned to single-dose ligelizumab 120 mg (n=42), which was administered at baseline followed by placebo every 4 weeks.
Weekly activity scores were used to monitor disease symptoms, including hives, itch, and angioedema. The primary endpoint was the achievement of complete hives response (weekly hives-severity score, 0) at week 12, which was used to identify and establish a dose-response relationship. The researchers also examined the association among all three treatment arms with complete symptom control, which was measured by a weekly urticaria activity score of 0 on a 0- to 42-point scale. Safety was also assessed during treatment.
At 12 weeks, none of the patients in the placebo group achieved complete control of hives, whereas 26% of patients in the omalizumab group did achieve complete hive control. Comparatively, complete control of hives was achieved in approximately 30% of patients in the 24-mg ligelizumab group, 51% of patients in the 27-mg ligelizumab group, and 42% of patients in the 240-mg ligelizumab group.
The percentage of patients in the 24-mg, 72-mg, and 240-mg ligelizumab groups who achieved complete control of symptoms by week 12 were 30%, 44%, and 40%, respectively. Only 26% of omalizumab-treated patients achieved complete symptom control, whereas none of the patients in the placebo group had complete control of symptoms at week 12. More patients in the 72-mg and 240-mg ligelizumab groups experienced adverse events compared with the other treatment groups.
Limitations of the study included the relatively short follow-up duration.
At the end of the 4-week administration interval, the researchers noted a partial relapse of symptoms with the 72-mg dose of ligelizumab. In response to these findings, the investigators suggest “a dose higher than 72 mg could potentially provide enough drug effect throughout the administration interval to minimize relapse of symptoms and offer sustained control of symptoms throughout the 4-week administration interval.”
Disclosure: This clinical trial was supported by Novartis Pharma. Please see the original reference for a full list of authors’ disclosures.
Maurer M, Giménez-Arnau AM, Sussman G, et al. Ligelizu mab for chronic spontaneous urticaria. N Engl J Med. 2019;381(14):1321-1332.