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Drugs. 2014 Jun;74(9):1029-39. doi: 10.1007/s40265-014-0242-4.
Ustekinumab (Stelara(®)) is a human monoclonal antibody that binds to the shared p40 subunit of interleukin (IL)-12 and IL-23, blocking signalling of their cognate receptors. It is established in the treatment of moderate-to-severe plaque psoriasis, but recently received approval in adults with active psoriatic arthritis. Tumour necrosis factor (TNF) inhibitors remain first-line biological agents for the treatment of psoriatic arthritis, but alternative agents are needed. This article summarises the pharmacology of ustekinumab and reviews its use in phase 3 trials in psoriatic arthritis. In these trials, subcutaneous ustekinumab 45 or 90 mg was significantly more effective than placebo, as determined by American College of Rheumatology response criteria at week 24. The drug was also associated with significantly greater efficacy than placebo with regard to secondary endpoints, including the Psoriasis Area and Severity Index ≥ 75 % response, enthesitis and dactylitis scores, radiographic progression and Health Assessment Questionnaire-Disability Index scores. Response to ustekinumab was maintained during long-term therapy (up to week 100), and was achieved with and without concomitant methotrexate. Ustekinumab was generally well tolerated, and the tolerability profile in psoriatic arthritis was similar to that reported in plaque psoriasis. Throughout long-term ustekinumab treatment, serious infection or major cardiovascular adverse events occurred rarely. More data are needed to clearly define the place of ustekinumab in psoriatic arthritis treatment algorithms. Meanwhile the drug is a valuable additional option for patients with psoriatic arthritis in whom the response to previous non-biological disease-modifying antirheumatic drugs has been inadequate, or for those who have failed anti-TNF therapy.
乌司奴单抗（喜达诺(®)）是一种人源化单克隆抗体，可与白细胞介素 (IL)-12 和 IL-23 的共享 p40 亚基结合，阻断其同源受体的信号传导。它在中重度斑块型银屑病的治疗中得到确立，但最近在活动性银屑病关节炎的成人患者中获得批准。肿瘤坏死因子 (TNF) 抑制剂仍然是治疗银屑病关节炎的一线生物制剂，但需要替代药物。本文总结了乌司奴单抗的药理学，并回顾了其在银屑病关节炎 3 期临床试验中的应用。在这些试验中，与安慰剂相比，乌司奴单抗皮下注射 45 或 90mg 在第 24 周时通过美国风湿病学会反应标准显著更有效。该药在次要终点方面也与安慰剂相比具有显著更高的疗效，包括银屑病面积和严重程度指数≥75%反应、附着点炎和指炎评分、放射学进展和健康评估问卷残疾指数评分。在长期治疗（最长至第 100 周）期间，乌司奴单抗的疗效得以维持，并且无论是否同时使用甲氨蝶呤，疗效都得以维持。乌司奴单抗总体耐受性良好，在银屑病关节炎中的耐受性与在斑块型银屑病中报告的相似。在长期乌司奴单抗治疗过程中，严重感染或主要心血管不良事件很少发生。需要更多的数据来明确确定乌司奴单抗在银屑病关节炎治疗方案中的地位。与此同时，对于那些对先前的非生物性疾病修饰抗风湿药物反应不足或对 TNF 治疗失败的银屑病关节炎患者，乌司奴单抗是一种有价值的额外选择。
