Add-on dupilumab improves chronic spontaneous urticaria treatment with antihistamines
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Key takeaways:
- A greater proportion of patients experienced improved scores with the addition of dupilumab to antihistamines.
- Dupilumab was well-tolerated with a safety profile consistent with other uses.
ANAHEIM, Calif. — Patients using dupilumab with H1 antihistamines for their chronic spontaneous urticaria experienced greater improvements over 24 weeks than those on antihistamines alone, according to a recent study.
“We know that many CSU [chronic spontaneous urticaria] patients are not well-controlled,” Chien-Chia Chuang, PhD, a health economist with Sanofi, said during her presentation at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting. “They are not well-managed by the standard of care, H1 antihistamines.”
Physicians typically use the reliable, patient-reported Urticaria Activity Score Over 7 Days (UAS7) instrument to assess disease activity, Chuang said, with subscales including Itch Severity Score Over 7 Days (ISS7) and Hive Severity Score Over 7 Days (HSS7).
Patients rate their itch and hives on a scale of 0 (none) to 3 (intense) for the ISS7 and HSS7, respectively, each day for 7 days, and daily scores are totaled for a final tally with a potential range between 0 and 42 in the UAS7.
“The greater the score, the more severe the itch, hives and disease activity,” Chuang said.
Previous literature has proposed a 9.5- to 10.5-point improvement in UAS7 as a threshold for a minimally important difference (MID), Chuang said, with a 4.5- to 5-point improvement for the ISS7 and a 5- to 5.5-point improvement for HSS7.
“However, in the past 10-plus years, there has been this kind of evolutionary change, and different kinds of methodologies have been proposed in assessing these types of MIDs,” Chuang said.
Also, Chuang said that the FDA suggested that industry sponsors apply cumulated distribution function (CDF) analysis in assessing all possible moving patient responder definitions to comprehensively evaluate differences between active treatment and placebo arms in studies.
Chuang and colleagues conducted the randomized, placebo-controlled, phase 3
LIBERTY-CSU CUPID Study A of dupilumab (Dupixent; Regeneron, Sanofi) in adults, adolescents and children aged 6 years and older with CSU who remained symptomatic despite standard-of-care H1 antihistamine use.
“Patients needed to have a diagnosis of CSU for at least 6 months before the screening,” Chuang said, along with the presence of itch and hives for more than 6 consecutive weeks despite H1 antihistamine use.
Also, patients had a baseline UAS7 score of 16 or greater as well as a baseline ISS7 score of 8 or greater, indicating at least moderate severity of CSU. Patients needed to be naive of omalizumab (Xolair; Genentech, Novartis) treatment as well.
After a 4-week screening period, researchers randomly assigned patients to receive dupilumab (n = 70) with dosages based on age and weight or a matched placebo (n = 68) for 24 weeks, followed by a 12-week follow-up period, in addition to their H1 antihistamine.
First, 74.2% of the patients assigned dupilumab and 50% of the patients assigned placebo achieved an 11-point reduction or higher in their UAS7 score, meeting the MID threshold.
CDF analysis revealed that the proportion of responders based on changes in UAS7 scores in week 24 was 20% greater or more for the dupilumab group compared with the placebo group across the range of responder thresholds between –6 and –19.
In addition, eight of 66 patients in the dupilumab group and 19 of 58 patients in the placebo group had no change or worse UAS7 scores at week 24 compared with baseline.
A total of 78.8% of the dupilumab group and 51.7% of the placebo group achieved a 5-point or greater reduction in their ISS7 and HSS7 scores, again meeting an MID threshold.
The proportion of responders based on change in ISS7 at week 24 was 20% greater or more for the dupilumab group compared with the placebo group across the range of responder thresholds between –2 and –11.
The CDF analysis here found nine of 66 patients in the dupilumab group and 19 of 58 patients in the placebo arm with no change or worse ISS7 scores at week 24 compared with baseline.
“In HSS7, we also show a similar trend,” Chuang said.
The proportion of responders based on change in HSS7 at week 24 was 20% greater or more for the dupilumab group compared with the placebo group across the range of responder thresholds between –1 and –12.
Again, the CDF analysis found eight of 66 patients in the dupilumab group and 20 of 58 in the placebo group reported no change or worse HSS7 scores at week 24 compared with baseline.
The researchers measured safety as well.
“[Dupilumab] is well-tolerated in the subjects, and the safety data are very comparable between the placebo and the dupilumab arms,” Chuang said. “Then the safety profile is very consistent with [dupilumab] safety data in other diseases.”
By group, 58.8% of the placebo group and 50% of the dupilumab group experienced any treatment-emergent adverse event (TEAE). Also, 7.4% of the placebo group and 2.9% of the dupilumab group experienced severe TEAEs.
TEAEs occurring among 5% or more of patients in either treatment group included skin and subcutaneous tissue disorders including CSU (placebo, 8.8%; dupilumab, 4.3%) and angioedema (7.4%; 1.4%) as well as general disorders and administrative site conditions (14.7%; 12.9%).
Based on these findings, the researchers concluded that greater proportions of patients receiving dupilumab with standard-of-care antihistamine treatment experienced improvements compared with patients receiving antihistamines alone.
“Regardless of where you look at the responder’s threshold,” Chuang said. “That’s the key finding from this research.”