Adis, a Wolters Kluwer Business, Auckland, New Zealand.
Drugs. 2011 Sep 10;71(13):1733-53. doi: 10.2165/11207530-000000000-00000.
Ustekinumab (Stelara™) is a human monoclonal antibody that binds to the p40 subunit common to both interleukin (IL)-12 and IL-23. It is indicated in the US for use in adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. In the EU, it is indicated for those who failed to respond to, have a contraindication to or are intolerant of other systemic therapies or phototherapy. This article reviews the efficacy and tolerability of ustekinumab in patients with moderate to severe plaque psoriasis, as well as summarizing its pharmacological properties. Ustekinumab attenuates the immune cell activation properties of IL-12 and IL-23. It interrupts the abnormal activation of signalling and cytokine cascades that underlie the pathology of psoriasis by reducing the expression of IL-12- and IL-23-induced cell surface markers that mediate skin homing, activation and cytokine release. In well designed, randomized clinical trials, regimens of subcutaneous ustekinumab 45 or 90 mg provided a rapid and durable improvement in psoriasis area severity index (PASI) scores for patients with moderate to severe plaque psoriasis. A significantly greater proportion of patients receiving ustekinuman 45 or 90 mg compared with those receiving placebo achieved a ≥75% improvement from baseline in PASI score following 12 weeks' treatment (primary endpoint). Improvements in PASI scores were evident following 2 weeks' treatment with ustekinumab and were sustained for up to 3 years. Treatment with ustekinumab 45 or 90 mg also improved health-related quality-of-life scores from baseline. Following 12 weeks' treatment, ustekinumab 45 or 90 mg was more effective than etanercept 50 mg twice weekly in providing symptomatic relief for patients with moderate to severe plaque psoriasis. Furthermore, ustekinumab treatment provided effective symptomatic improvement for almost half of the patients who showed no response to 12 weeks' treatment with etanercept. More limited data indicate that ustekinumab also improves the symptoms of arthritis in patients with plaque psoriasis and psoriatic arthritis. Subcutaneous ustekinumab was generally well tolerated in clinical trials; most adverse events were mild in intensity and did not require dosage adjustment. A pooled analysis of clinical trial data indicated no specific patterns of infection for recipients of ustekinumab and that infection rates remained stable following cumulative exposure to the agent. In conclusion, subcutaneous ustekinumab provides an effective and well tolerated alternative for the symptomatic treatment of patients with moderate to severe plaque psoriasis.
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 p40 亚单位结合。在美国，它被批准用于中度至重度斑块型银屑病的成年患者，这些患者适合光疗或全身治疗。在欧盟，它被批准用于那些对其他全身治疗或光疗无反应、有禁忌或不耐受的患者。本文综述了乌司奴单抗在中度至重度斑块型银屑病患者中的疗效和耐受性，并总结了其药理学特性。乌司奴单抗可减弱 IL-12 和 IL-23 的免疫细胞激活特性。它通过减少介导皮肤归巢、激活和细胞因子释放的 IL-12 和 IL-23 诱导的细胞表面标志物的表达，阻断导致银屑病发病机制的异常信号和细胞因子级联的异常激活。在设计良好的随机临床试验中，接受乌司奴单抗 45 或 90mg 皮下注射的患者，其银屑病面积和严重程度指数（PASI）评分迅速且持久改善。与安慰剂相比，接受乌司奴单抗 45 或 90mg 治疗的患者在 12 周治疗后，有更大比例的患者 PASI 评分较基线改善≥75%（主要终点）。乌司奴单抗治疗 2 周后 PASI 评分即有改善，并可持续长达 3 年。乌司奴单抗治疗还可改善基线健康相关生活质量评分。接受乌司奴单抗 45 或 90mg 治疗 12 周后，与依那西普 50mg 每周 2 次相比，前者在缓解中度至重度斑块型银屑病患者的症状方面更有效。此外，乌司奴单抗治疗几乎可使一半对依那西普治疗 12 周无反应的患者症状得到有效改善。有限的数据表明，乌司奴单抗还可改善斑块型银屑病和银屑病关节炎患者的关节炎症状。在临床试验中，乌司奴单抗一般具有良好的耐受性；大多数不良反应的严重程度为轻度，不需要调整剂量。一项临床试验数据的汇总分析表明，接受乌司奴单抗治疗的患者不存在特定的感染模式，且随着药物累积暴露，感染率保持稳定。总之，乌司奴单抗是一种有效的、耐受性良好的治疗中度至重度斑块型银屑病的替代药物。
