Dupilumab improves outcomes in H1 antihistamine-resistant chronic spontaneous urticaria
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LOUISVILLE, Ky. — Patients with chronic spontaneous urticaria experienced improvements with dupilumab, according to a study presented at the American College of Asthma & Immunology Annual Scientific Meeting.
These improvements were clinically meaningful and statistically significant for these patients, who previously had remained symptomatic despite H1 antihistamine treatment, the researchers wrote.
“About 50 percent of patients don’t respond to typical H1 antihistamines, even at four times the licensed dose,” Thomas B. Casale, MD, professor of internal medicine and pediatrics and chief of clinical and translational research in the division of allergy and immunology at University of South Florida Morsani College of Medicine, said during the presentation.
“So, there’s a need for therapies other than omalizumab (Xolair; Genentech, Novartis) as the only treatment that’s approved. We know that other drugs do work, but we don’t have any good data with them,” Casale continued.
The randomized and placebo-controlled phase 3 LIBERTY-CSU-CUPID Study A comprised 138 patients aged 6 years and older who had been experiencing chronic spontaneous urticaria (CSU) for 6 months or longer, with itching and hives for 6 weeks or longer despite H1 antihistamine use. Also, none of these patients had used omalizumab. The overall population had a baseline medium serum total IgE of 101.0 IU/mL.
“Time since first diagnosis with CSU was generally over 5 years and approaching 6 years,” Casale added.
Overall, 70 patients received dupilumab (Dupixent; Sanofi, Regeneron). Adults and adolescents aged 12 to 17 years who weighed more than 60 kg began with a loading dose of 600 mg, with 300 mg doses following every 2 weeks. Adolescents aged 12 to 17 and children aged 6 and older who weighed more than 30 kg but less than 60 kg began with a 400 mg loading dose with 200 mg doses every 2 weeks after that. Children aged 6 to 12 years who weighed between 15 kg and 30 kg began with a 600 mg loading dose with 300 mg doses following every 4 weeks.
Another 68 patients received placebo. All doses in the treatment and placebo groups were subcutaneous and administered as add-ons to their H1 antihistamine treatment.
At baseline and at week 24, the researchers assessed their 7-day Itch Severity Score (ISS7), Hives Severity Score (HSS7) and Urticaria Activity Score (UAS7). Mean baseline scores for the treatment vs. placebo groups included 16.1 vs. 15.7 for ISS7 and 31.9 vs. 30.8 for UAS7.
At week 24, least squares (LS) mean changes from baseline in ISS7 included –10.2 for dupilumab and –6 for placebo (LS mean difference, –4.2; P = .0005). For UAS7, they included –20.5 for dupilumab and –12 for placebo (LS mean difference, –8.5; P = .0003).
The treatment group also experienced significantly reduced ISS7, HSS7 and UAS7 totals at week 24 regardless of baseline serum total IgE, the researchers continued.
Specifically, for those who received treatment vs. placebo, patients with baseline serum total IgE less than 100 IU/mL and 100 IU/mL or greater showed similarly greater LS mean differences in ISS7 (–4.2 and –4.6), HSS7 (–4.2 and –6.1) and UAS7 (–8.2 and –10.6).
There were 35 (50%) treatment-emergent adverse events in the treatment group and 40 (58.8%) in the placebo group. Also, there were eight (11.4%) injection-site reactions in the treatment group and nine (13.2%) in the placebo group.
Also, there were no cases of conjunctivitis in the treatment group and one case (1.5%) in the placebo group. Finally, there were two (2.9%) serious treatment-emergent adverse events in the treatment group and five (7.4%) in the placebo group.
“The safety summary is unremarkable, except for the fact that the exacerbations of chronic spontaneous urticaria and exacerbations of angioedema were greater in the placebo group, which you would expect,” Casale said.
“In summary, dupilumab demonstrated clinically meaningful and statistically significant improvements in signs and symptoms of H1 antihistamine-resistant CSU regardless of IgE level, and it was also well tolerated and appeared safe,” Casale concluded.