Scanlon James V, Exter Benjamin P, Steinberg Michael, Jarvis Courtney I
School of Pharmacy, Biogen Idec/Massachusetts College of Pharmacy and Health Sciences, Worcester-Manchester, MA 01608, USA.
Ann Pharmacother. 2009 Sep;43(9):1456-65. doi: 10.1345/aph.1M151. Epub 2009 Aug 11.
To systematically review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of ustekinumab to inform pharmacists and other healthcare professionals of this new biologic therapy for psoriasis.
A search of PubMed/MEDLINE, EMBASE, and International Pharmaceutical Abstracts was performed through July 2009, limited to publications in English, using the search terms CNTO-1275, ustekinumab, interleukin-12, interleukin-23, and/or psoriasis to identify literature sources. References from the retrieved articles were also evaluated to identify relevant literature. An abstract from a Congress of the European Academy of Dermatology and Venereology and unpublished Phase 3 clinical trials in progress (using www.clinicaltrials.gov) were also reviewed. The Food and Drug Administration, European Medicines Agency, and Health Canada Web sites were used to retrieve product monographs, regulatory guidances, and advisory committee briefing packets.
All available studies relevant to the pharmacology, pharmacokinetics, and clinical safety/efficacy of ustekinumab for the treatment of psoriasis were included, with preference for human data.
Ustekinumab, an anti-interleukin-12/23 monoclonal antibody, achieved the primary endpoint of 75% reduction in the Psoriasis Area and Severity Index score in a large proportion of patients in the Phase 3 PHOENIX trials. Commensurate improvements were also seen in the Physician's Global Assessment and Dermatology Life Quality Index scores. These efficacy results were reproduced in the ACCEPT trial, demonstrating superiority of ustekinumab to etanercept. The frequency of adverse events was similar between ustekinumab and placebo; common adverse events reported included nasopharyngitis, upper respiratory tract infection, headache, arthralgia, cough, and injection site reactions. Phase 3 studies indicate that the optimal dosing appears to be 45 mg for patients weighing less than 100 kg or 90 mg for patients weighing more than 100 kg, with both doses administered subcutaneously. In these studies, the second dose was given 4 weeks after the first and then every 8-12 weeks thereafter, based upon response.
Ustekinumab, a promising new therapy, reduces the extent and severity of psoriasis and was well tolerated in clinical trials. Ongoing clinical trials will allow clinicians to further assess the efficacy/safety profile of this novel biologic.
系统回顾优特克单抗的药理学、药代动力学、临床疗效及安全性，以便向药剂师及其他医疗专业人员介绍这种治疗银屑病的新型生物疗法。
检索截至2009年7月的PubMed/MEDLINE、EMBASE及国际药学文摘数据库，检索词限定为CNTO-1275、优特克单抗、白细胞介素-12、白细胞介素-23及/或银屑病，仅纳入英文文献以确定文献来源。对检索到的文章的参考文献也进行评估以确定相关文献。还查阅了欧洲皮肤病与性病学会大会的一篇摘要及正在进行的未发表的3期临床试验（使用www.clinicaltrials.gov）。利用美国食品药品监督管理局、欧洲药品管理局及加拿大卫生部网站获取产品说明书、监管指南及咨询委员会简报文件。
纳入所有与优特克单抗治疗银屑病的药理学、药代动力学及临床安全性/疗效相关的现有研究，优先选择人体数据。
优特克单抗是一种抗白细胞介素-12/23单克隆抗体，在3期PHOENIX试验的大部分患者中达到了银屑病面积和严重程度指数评分降低75%的主要终点。在医师整体评估和皮肤病生活质量指数评分方面也有相应改善。这些疗效结果在ACCEPT试验中得到重现，证明优特克单抗优于依那西普。优特克单抗与安慰剂的不良事件发生率相似；报告的常见不良事件包括鼻咽炎、上呼吸道感染、头痛、关节痛、咳嗽及注射部位反应。3期研究表明，体重小于100 kg的患者最佳剂量似乎为45 mg，体重大于100 kg的患者为90 mg，两种剂量均皮下注射。在这些研究中，第二剂在第一剂后4周给药，此后根据反应每8 - 12周给药一次。
优特克单抗是一种有前景的新疗法，可减轻银屑病的范围和严重程度，在临床试验中耐受性良好。正在进行的临床试验将使临床医生能够进一步评估这种新型生物制剂的疗效/安全性。
