Ligelizumab for Chronic Spontaneous Urticaria

被引:193
|
作者
Maurer, Marcus [1 ]
Gimenez-Arnau, Ana M. [6 ]
Sussman, Gordon [7 ,8 ]
Metz, Martin [1 ]
Baker, Diane R. [11 ]
Bauer, Andrea [2 ]
Bernstein, Jonathan A. [12 ,13 ]
Brehler, Randolf [3 ]
Chu, Chia-Yu [14 ,15 ]
Chung, Wen-Hung [16 ]
Danilycheva, Inna [17 ]
Grattan, Clive [19 ]
Hebert, Jacques [9 ]
Katelaris, Constance [23 ,24 ]
Makris, Michael [27 ]
Meshkova, Raisa [18 ]
Savic, Sinisa [20 ,21 ,22 ]
Sinclair, Rodney [25 ,26 ]
Sitz, Karl [28 ]
Staubach, Petra [4 ]
Wedi, Bettina [5 ]
Loeffler, Juergen [29 ]
Barve, Avantika [30 ]
Kobayashi, Kenneth [10 ,30 ]
Hua, Eva [31 ]
Severin, Thomas [29 ]
Janocha, Reinhold [29 ]
机构
[1] Charite Univ Med Berlin, Dept Dermatol & Allergy, Berlin, Germany
[2] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Univ Allergy Ctr, Dept Dermatol, Dresden, Germany
[3] Univ Hosp Munster, Dept Dermatol, Munster, Germany
[4] Univ Med Ctr Mainz, Dept Dermatol, Mainz, Germany
[5] Hannover Med Sch, Dept Dermatol & Allergy, Comprehens Allergy Ctr, Hannover, Germany
[6] Univ Autonoma Barcelona, Dept Dermatol, Hosp Mar, Inst Hosp Mar Invest Med, Barcelona, Spain
[7] St Michaels Hosp, Div Allergy & Clin Immunol, Toronto, ON, Canada
[8] Univ Toronto, Toronto, ON, Canada
[9] Ctr Hosp Univ Quebec, Serv Allergie, Ctr Hosp Univ Laval, Quebec City, PQ, Canada
[10] Univ Ottawa, Dept Med, Ottawa, ON, Canada
[11] Baker Allergy Asthma & Dermatol Clin, Portland, OR USA
[12] Univ Cincinnati, Coll Med, Dept Internal Med, Div Immunol Rheumatol & Allergy, Cincinnati, OH USA
[13] Univ Cincinnati, Coll Med, Bernstein Clin Res Ctr, Cincinnati, OH USA
[14] Natl Taiwan Univ Hosp, Dept Dermatol, Taipei, Taiwan
[15] Natl Taiwan Univ, Coll Med, Taipei, Taiwan
[16] Chang Gung Mem Hosp, Dept Dermatol, Taipei, Taiwan
[17] Fed Med Biol Agcy Russia, Natl Res Ctr, Inst Immunol, Moscow, Russia
[18] Smolensk State Med Univ, Dept Clin Immunol & Allergol, Smolensk, Russia
[19] Guys & St Thomas Hosp NHS Fdn Trust, St Johns Inst Dermatol, London, England
[20] Leeds Biomed Res Ctr, Natl Inst Hlth Res, Leeds, W Yorkshire, England
[21] St James Univ Hosp, Leeds Inst Rheumat & Musculoskeletal Med, Leeds, W Yorkshire, England
[22] St James Univ Hosp, Dept Clin Immunol & Allergy, Leeds, W Yorkshire, England
[23] Western Sydney Univ, Sch Med, Campbelltown, NSW, Australia
[24] Campbelltown Hosp, Immunol & Allergy Unit, Campbelltown, NSW, Australia
[25] Sinclair Dermatol, Melbourne, Vic, Australia
[26] Epworth Med Fdn, Melbourne, Vic, Australia
[27] Attikon Univ Hosp, Dept Dermatol & Venereol 2, Athens, Greece
[28] Little Rock Allergy & Asthma Clin, Little Rock, AR USA
[29] Novartis Pharmaceut, Basel, Switzerland
[30] Novartis Pharmaceut, E Hanover, NJ USA
[31] Shanghai Novartis Trading, Shanghai, Peoples R China
来源
NEW ENGLAND JOURNAL OF MEDICINE | 2019年 / 381卷 / 14期
关键词
CHRONIC IDIOPATHIC/SPONTANEOUS URTICARIA; OMALIZUMAB; EPIDEMIOLOGY;
D O I
10.1056/NEJMoa1900408
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
This dose-response trial of ligelizumab showed that approximately half the patients treated with 240 mg of ligelizumab had complete resolution of hives, as compared with only approximately one quarter of the patients treated with the recommended dose of omalizumab. 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 H-1-antihistamines at approved or increased doses, alone or in combination with H-2-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.).
引用
收藏
页码:1321 / 1332
页数:12
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