新藥Ligelizumab可用於治療慢性自發性蕁麻疹
作者：
小柯機器人發布時間：2019/10/9 13:12:45
近日，德國柏林中央大學Marcus Maurer
Ligelizumab是新一代的高親和力人源化單克隆抗IgE抗體。與奧馬珠單抗和安慰劑相比，Ligelizumab用於治療中重度慢性自發性蕁麻疹患者的劑量-反應關係、有效性和安全性的數據目前很有限。
在這項臨床2b期的劑量發現試驗中，研究組隨機分配患者接受Ligelizumab劑量為24mg、72mg和240mg，奧馬珠單抗300mg或安慰劑進行治療。通過每周活動評分來監測蕁麻疹、瘙癢和血管性水腫，共0-21分，分數越高病情越嚴重。
共有382名患者接受了隨機分組。在第12周，服用24mg、72mg和240mg Ligelizumab的患者中，分別有30%、51%和42%的蕁麻疹得到完全控制，而奧馬珠單抗組和安慰劑組則分別為26%和0。劑量-反應關係得以建立。在第12周時，服用24mg、72mg和240mg Ligelizumab的患者中，分別有30％、44％和40％的患者症狀完全改善，而奧馬珠單抗組和安慰劑組則分別為26%和0。在這項小型短期的試驗中，未發生關於Ligelizumab或奧馬珠單抗的安全問題。
總之，與奧馬珠單抗或安慰劑相比，採用Ligelizumab 72mg或240mg進行治療的患者能完全控制慢性自發性蕁麻疹的症狀。
據悉，對於大多數慢性自發性蕁麻疹患者，很多目前可用的治療方法並不能完全控制症狀。
附：英文原文
Title: Ligelizumab for Chronic Spontaneous Urticaria
Author: Marcus Maurer, Ana M. Giménez-Arnau, Gordon Sussman, Martin Metz, Diane R. Baker, Andrea Bauer, Jonathan A. Bernstein, Randolf Brehler, Chia-Yu Chu, Wen-Hung Chung, Inna Danilycheva, Clive Grattan, Jacques Hébert, Constance Katelaris, Michael Makris, Raisa Meshkova, Sinisa Savic, Rodney Sinclair, Karl Sitz, Petra Staubach, Bettina Wedi, Jürgen Lffler, Avantika Barve, Kenneth Kobayashi, Eva Hua, Thomas Severin, Reinhold Janocha
Issue&Volume: Vol 381 No 14
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.
DOI: 10.1056/NEJMoa1900408
Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1900408