Ixekizumab: a new anti-IL-17A monoclonal antibody therapy for moderate-to severe plaque psoriasis

被引:17
作者
Blauvelt, Andrew [1 ]
机构
[1] Oregon Med Res Ctr, 9495 SW Locust St,Suite G, Portland, OR 97223 USA
关键词
Psoriasis; interleukin-17; anti-IL17A; ixekizumab; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; PHASE-II; MAINTENANCE THERAPY; CLINICAL-RESPONSE; OPEN-LABEL; SAFETY; EFFICACY; TH17; SECUKINUMAB;
D O I
10.1517/14712598.2016.1132695
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Introduction: Psoriasis is a common, systemic, inflammatory disease with prominent skin and joint manifestations. Interleukin 17A (IL-17A) has been identified as a key effector cytokine that mediates immunopathogenesis of psoriasis. Ixekizumab, a humanized monoclonal antibody that targets IL-17A, has been found in clinical trials to dramatically reduce signs and symptoms of moderate-to-severe plaque psoriasis.Areas covered: The following areas are discussed: the basic structure and function of IL-17A, its role in the pathogenesis of psoriasis, the safety and efficacy of ixekizumab in clinical trials reported to date, and the possible impact of ixekizumab on the future therapeutic market for psoriasis.Expert opinion: A large proportion of patients with psoriasis achieve clear or near clear skin during treatment with ixekizumab in a rapid and sustained manner. This supports the idea that IL-17A plays a central role in psoriasis immunopathogenesis. While ixekizumab has been shown to be safe in trials up to 60 weeks, long-term safety data are not yet available. Because its efficacy is higher than all previously approved drugs for psoriasis thus far, approval and use of ixekizumab may lead to a treatment paradigm change for psoriasis, where clear or near clear skin becomes an acceptable and achievable treatment goal.
引用
收藏
页码:255 / 263
页数:9
相关论文
共 48 条
[1]   Targeting the IL-17-TH17 pathway [J].
Bartlett, Hilary S. ;
Million, Ryan P. .
NATURE REVIEWS DRUG DISCOVERY, 2015, 14 (01) :11-12
[2]   Secukinumab administration by pre-filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE) [J].
Blauvelt, A. ;
Prinz, J. C. ;
Gottlieb, A. B. ;
Kingo, K. ;
Sofen, H. ;
Ruer-Mulard, M. ;
Singh, V. ;
Pathan, R. ;
Papavassilis, C. ;
Cooper, S. .
BRITISH JOURNAL OF DERMATOLOGY, 2015, 172 (02) :484-493
[3]  
Blauvelt A., 2007, Expert Rev. Dermatol, V2, P69, DOI DOI 10.1586/17469872.2.1.69
[4]  
Blauvelt A, 2015, J DRUGS DERMATOL, V14, P805
[5]   IL-23/IL-17A Dysfunction Phenotypes Inform Possible Clinical Effects from Anti-IL-17A Therapies [J].
Blauvelt, Andrew ;
Lebwohl, Mark G. ;
Bissonnette, Robert .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2015, 135 (08) :1946-1953
[6]   IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis [J].
Chan, Jason R. ;
Blumenschein, Wendy ;
Murphy, Erin ;
Diveu, Caroline ;
Wiekowski, Maria ;
Abbondanzo, Susan ;
Lucian, Linda ;
Geissler, Richard ;
Brodie, Scott ;
Kimball, Alexa B. ;
Gorman, Daniel M. ;
Smith, Kathleen ;
Malefyt, Rene de Waal ;
Kastelein, Robert A. ;
McClanahan, Terrill K. ;
Bowman, Edward P. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (12) :2577-2587
[7]   IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice [J].
Cho, John S. ;
Pietras, Eric M. ;
Garcia, Nairy C. ;
Ramos, Romela Irene ;
Farzam, David M. ;
Monroe, Holly R. ;
Magorien, Julie E. ;
Blauvelt, Andrew ;
Kolls, Jay K. ;
Cheung, Ambrose L. ;
Cheng, Genhong ;
Modlin, Robert L. ;
Miller, Lloyd S. .
JOURNAL OF CLINICAL INVESTIGATION, 2010, 120 (05) :1762-1773
[8]   The IL23R R381Q Gene Variant Protects against Immune-Mediated Diseases by Impairing IL-23-Induced Th17 Effector Response in Humans [J].
Di Meglio, Paola ;
Di Cesare, Antonella ;
Laggner, Ute ;
Chu, Chung-Ching ;
Napolitano, Luca ;
Villanova, Federica ;
Tosi, Isabella ;
Capon, Francesca ;
Trembath, Richard C. ;
Peris, Ketty ;
Nestle, Frank O. .
PLOS ONE, 2011, 6 (02)
[9]   A high level of clinical response is associated with improved patient-reported outcomes in psoriasis: analyses from a phase 2 study in patients treated with ixekizumab [J].
Edson-Heredia, E. ;
Banerjee, S. ;
Zhu, B. ;
Maeda-Chubachi, T. ;
Cameron, G. S. ;
Shen, W. ;
Heffernan, M. P. ;
Gordon, K. B. ;
Leonardi, C. L. .
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY, 2016, 30 (05) :864-865
[10]   Pathophysiology of psoriasis: Recent advances on IL-23 and TH17 cytokines [J].
Fitch E. ;
Harper E. ;
Skorcheva I. ;
Kurtz S.E. ;
Blauvelt A. .
Current Rheumatology Reports, 2007, 9 (6) :461-467