近日，德国柏林中央大学Marcus Maurer及其小组的最新研究提出，Ligelizumab可用于治疗慢性自发性荨麻疹。该研究于2019年10月3日发表于国际一流学术期刊《新英格兰医学杂志》。

Ligelizumab是新一代的高亲和力人源化单克隆抗IgE抗体。与奥马珠单抗和安慰剂相比，Ligelizumab用于治疗中重度慢性自发性荨麻疹患者的剂量-反应关系、有效性和安全性的数据目前很有限。

在这项临床2b期的剂量发现试验中，研究组随机分配患者接受Ligelizumab剂量为24mg、72mg和240mg，奥马珠单抗300mg或安慰剂进行治疗。通过每周活动评分来监测荨麻疹、瘙痒和血管性水肿，共0-21分，分数越高病情越严重。

共有382名患者接受了随机分组。在第12周，服用24mg、72mg和240mg Ligelizumab的患者中，分别有30%、51%和42%的荨麻疹得到完全控制，而奥马珠单抗组和安慰剂组则分别为26%和0。剂量-反应关系得以建立。在第12周时，服用24mg、72mg和240mg Ligelizumab的患者中，分别有30％、44％和40％的患者症状完全改善，而奥马珠单抗组和安慰剂组则分别为26%和0。在这项小型短期的试验中，未发生关于Ligelizumab或奥马珠单抗的安全问题。

总之，与奥马珠单抗或安慰剂相比，采用Ligelizumab 72mg或240mg进行治疗的患者能完全控制慢性自发性荨麻疹的症状。

据悉，对于大多数慢性自发性荨麻疹患者，很多目前可用的治疗方法并不能完全控制症状。

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