Maldonado-Ficco Hernan, Perez-Alamino Rodolfo, Maldonado-Cocco José A
Rheumatology Section, Department of Internal Medicine, Hospital San Antonio de Padua, Cordoba, Río Cuarto, Argentina.
Rheumatology Section, Department of Internal Medicine, Hospital Avellaneda, Tucumán, Argentina.
Clin Rheumatol. 2016 Sep;35(9):2151-61. doi: 10.1007/s10067-016-3350-6. Epub 2016 Jul 20.
Psoriatic arthritis (PsA) is the second most common chronic inflammatory joint disease. Ankylosing spondylitis (AS) is another less common but equally chronic and disabling spondyloarthritis (SpA). Therapeutic agents for the treatment of these diseases have been somewhat lacking as compared with those available for rheumatoid arthritis, which represents a significant challenge for both the treating physician and the pharmaceutical industry. A promising development for our understanding of the physiopathology of PsA and AS involves new targets to interrupt IL-17 and IL-12/IL-23 pathways. Up to 30-40 % of SpA patients have inadequate or poor response, or are intolerant to anti-TNF therapies. Therefore, there has been a clear unmet medical need in an important group of these patients. As a result, new therapeutic targets have emerged for the treatment of both axial and peripheral SpA. Interleukin 17 (IL-17) is a pro-inflammatory cytokine that is increased in psoriatic lesions as well as in the synovial fluid of patients with PsA and in sites of enthesitis in SpA. IL-23 has been shown to play an important role in the polarization of CD4+ T-cells to become IL-17 producers. Based on these evidences, blockade of the cytokine IL-17 or its receptors was considered to have therapeutic implications for the treatment of psoriasis, as well as PsA and AS.This article presents a thorough review of an IL-17 A blocking agent, its mechanism of action, its clinical efficacy and its therapeutic safety.
银屑病关节炎(PsA)是第二常见的慢性炎症性关节疾病。强直性脊柱炎(AS)是另一种较不常见但同样为慢性且致残的脊柱关节炎(SpA)。与类风湿关节炎相比,治疗这些疾病的治疗药物有所欠缺,这对治疗医生和制药行业都构成了重大挑战。对我们理解PsA和AS的生理病理学而言,一个有前景的进展涉及中断IL-17和IL-12/IL-23通路的新靶点。高达30%-40%的SpA患者对抗TNF治疗反应不足或不佳,或不耐受。因此,在这类重要患者群体中存在明显未满足的医疗需求。结果,出现了用于治疗轴性和外周性SpA的新治疗靶点。白细胞介素17(IL-17)是一种促炎细胞因子,在银屑病皮损、PsA患者的滑液以及SpA的附着点部位均升高。已证明IL-23在CD4+ T细胞极化为IL-17产生细胞的过程中起重要作用。基于这些证据,细胞因子IL-17或其受体的阻断被认为对银屑病以及PsA和AS的治疗具有治疗意义。本文对一种IL-17A阻断剂、其作用机制、临床疗效和治疗安全性进行了全面综述。