Ligelizumab for chronic spontaneous urticaria
Journal
New England Journal of Medicine
Journal Volume
381
Journal Issue
14
Pages
1321-1332
Date Issued
2019
Author(s)
Maurer M.
Gim?nez-Arnau A.M.
Sussman G.
Metz M.
Baker D.R.
Bauer A.
Bernstein J.A.
Brehler R.
Chung W.-H.
Danilycheva I.
Grattan C.
H?bert J.
Katelaris C.
Makris M.
Meshkova R.
Savic S.
Sinclair R.
Sitz K.
Staubach P.
Wedi B.
L?ffler J.
Barve A.
Kobayashi K.
Hua E.
Severin T.
Janocha R.
Abstract
BACKGROUND In the majority of patients with chronic spontaneous urticaria, most currently available therapies do not result in complete symptom control. Ligelizumab is a next-generation high-affinity humanized monoclonal anti-IgE antibody. Data are limited regarding the dose–response relationship of ligelizumab and the efficacy and safety of ligelizumab as compared with omalizumab and placebo in patients who have moderate-to-severe chronic spontaneous urticaria that is inadequately controlled with H1-antihistamines at approved or increased doses, alone or in combination with H2-antihistamines or leukotriene-receptor antagonists. METHODS In a phase 2b dose-finding trial, we randomly assigned patients to receive ligelizumab at a dose of 24 mg, 72 mg, or 240 mg, omalizumab at a dose of 300 mg, or placebo, administered subcutaneously every 4 weeks for a period of 20 weeks, or a single 120-mg dose of ligelizumab. Disease symptoms of hives, itch, and angioedema were monitored by means of weekly activity scores. The main objective was to determine a dose–response relationship for the complete control of hives (indicated by a weekly hives-severity score of 0, on a scale from 0 to 21, with higher scores indicating greater severity); the primary end point of this response was assessed at week 12. Complete symptom control was indicated by a weekly urticaria activity score of 0 (on a scale from 0 to 42, with higher scores indicating greater severity). Safety was analyzed throughout the trial. RESULTS A total of 382 patients underwent randomization. At week 12, a total of 30%, 51%, and 42% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of hives, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. A dose–response relationship was established. At week 12, a total of 30%, 44%, and 40% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of symptoms, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. In this small and short trial, no safety concerns regarding ligelizumab or omalizumab emerged. CONCLUSIONS A higher percentage of patients had complete control of symptoms of chronic spontaneous urticaria with ligelizumab therapy of 72 mg or 240 mg than with omalizumab or placebo. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT02477332.) ? 2019 Massachusetts Medical Society.
SDGs
Other Subjects
ligelizumab; omalizumab; placebo; antiallergic agent; antiidiotypic antibody; immunoglobulin E; ligelizumab; monoclonal antibody; omalizumab; adult; aged; Article; chronic urticaria; clinical assessment; controlled study; disease severity; dose response; double blind procedure; drug efficacy; drug safety; female; headache; health care quality; human; injection site erythema; major clinical study; male; multicenter study; phase 2 clinical trial; priority journal; randomized controlled trial; skin disease assessment; symptom; treatment duration; treatment response; viral upper respiratory tract infection; blood; chronic disease; clinical trial; comparative study; drug administration; immunology; middle aged; patient acuity; remission; urticaria; young adult; Adult; Aged; Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Immunoglobulin E; Male; Middle Aged; Omalizumab; Patient Acuity; Remission Induction; Urticaria; Young Adult
Publisher
Massachussetts Medical Society
Type
journal article