AI Article Synopsis
- Chronic urticaria (CU) is a challenging condition driven by mast cells, and standard treatments like antihistamines often fail; lirentelimab, a targeted therapy, shows promise by specifically inhibiting these mast cells and reducing eosinophils.
- A phase 2a study evaluated the safety and effectiveness of lirentelimab in 45 CU patients who did not respond to high doses of antihistamines, measuring changes in their Urticaria Control Test scores after 22 weeks.
- Results indicated a significant improvement in itch and hive control, particularly among omalizumab-naive and omalizumab-refractory patients, with most adverse effects being mild and temporary, pointing towards lirentelimab
Article Abstract
Background: Chronic urticaria (CU) is a debilitating mast cell-driven disease, often refractory to standard therapy (ie, antihistamines). Lirentelimab, an anti-sialic acid-binding immunoglobulin-like lectin 8 mAb, selectively inhibits mast cells and depletes eosinophils.
Objective: We sought to determine safety and efficacy of lirentelimab in patients with CU.
Methods: This phase 2a study enrolled patients with CU refractory to up to 4-fold H1-antihistamine doses. Patients received 6 monthly intravenous doses of lirentelimab (0.3, 1, and up to 3 mg/kg). Primary efficacy end point was change in Urticaria Control Test score at week 22. Urticaria Activity Score weekly average (UAS7) was assessed in patients with chronic spontaneous urticaria (CSU), and Cholinergic UAS7 was used for patients with cholinergic urticaria (CholU).
Results: A total of 45 patients were enrolled in 4 cohorts (n = 13 omalizumab-naive CSU, n = 11 omalizumab-refractory CSU, n = 11 CholU, n = 10 symptomatic dermographism). Urticaria Control Test scores increased with lirentelimab across cohorts, with mean changes at week 22 of 11.1 ± 4.1, 4.8 ± 7.0, 6.5 ± 6.2, and 3.4 ± 4.1 and complete response rates (Urticaria Control Test score ≥ 12) of 92%, 36%, 82%, and 40%, respectively. In omalizumab-naive and omalizumab-refractory patients with CSU, disease activity decreased at week 22 (mean UAS7 change, -73% and -47%, respectively), with UAS7 response rates (≥50% reduction) of 77% and 45%, respectively. In patients with symptomatic dermographism, 50% (5 of 10) and 40% (4 of 10) had complete itch and hive resolution by FricTest, respectively, and 100% (7 of 7) evaluable patients with CholU had negative responses to Pulse-Controlled Ergometry exercise test. Most common adverse events included infusion-related reactions (43%; all mild/moderate and transient), nasopharyngitis (21%), and headache (19%). No treatment-related serious adverse events occurred.
Conclusions: Lirentelimab demonstrated activity across 3 forms of antihistamine-refractory CU.
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| http://dx.doi.org/10.1016/j.jaci.2021.12.772 | DOI Listing |
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