Department of Dermatology, University Medical Centre St Radboud, Nijmegen, The Netherlands.
J Eur Acad Dermatol Venereol. 2010 Oct;24 Suppl 6:5-9. doi: 10.1111/j.1468-3083.2010.03830.x.
Recent research has identified the importance of interleukin 12 (IL)-12 and IL-23 in the immunopathogenesis of psoriasis. The p40 subunit common to IL-12 and IL-23 is an attractive target for selective therapy. Clinical study data are available for two anti-IL-12/23 therapies: ustekinumab (CNTO 1275, approved in 2009 for treatment of plaque psoriasis) and ABT-874. The Phase 3 clinical trials PHOENIX 1 and PHOENIX 2 have shown significant benefit for ustekinumab in moderate-to-severe plaque psoriasis, with PASI 75 response rates ranging from 66% at week 12 (after two injections) and rising to 85% at week 24 (after three injections). Withdrawal of treatment led to a gradual return of psoriasis whereas continued therapy every 12 weeks with ustekinumab maintained PASI 75 response. Analysis of safety data demonstrated a safety profile similar to placebo at week 12 and did not reveal any major safety concerns in blocking IL-12 and IL-23 for periods as long as 18 months. Phase 2 data indicate that ABT-874 is also efficacious in the treatment of moderate-to-severe plaque psoriasis across a range of dosing strategies.
最近的研究已经确定了白细胞介素 12（IL-12）和白细胞介素 23（IL-23）在银屑病发病机制中的重要性。IL-12 和 IL-23 的共同 p40 亚基是选择性治疗的一个有吸引力的靶点。有两种抗 IL-12/23 疗法的临床研究数据：乌司奴单抗（CNTO 1275，2009 年批准用于治疗斑块状银屑病）和 ABT-874。三期临床试验 PHOENIX 1 和 PHOENIX 2 表明乌司奴单抗在中重度斑块状银屑病中具有显著疗效，PASI 75 应答率从第 12 周（两次注射后）的 66%上升到第 24 周（三次注射后）的 85%。停止治疗后银屑病逐渐复发，而每 12 周用乌司奴单抗维持治疗则保持 PASI 75 应答。安全性数据分析显示，第 12 周时的安全性与安慰剂相似，在长达 18 个月的时间内阻断 IL-12 和 IL-23 并没有发现任何重大安全问题。二期数据表明，ABT-874 对多种剂量方案治疗中重度斑块状银屑病也有效。
