Wilhelm Sheila M, McKenney Kathleen A, Rivait Kelly N, Kale-Pradhan Pramodini B
Department of Pharmacy Services, Harper University Hospital, Detroit, Michigan, USA.
Clin Ther. 2008 Feb;30(2):223-30. doi: 10.1016/j.clinthera.2008.02.014.
Infliximab is a chimeric immunoglobulin G1kappa monoclonal antibody that binds with high affinity and specificity to the soluble form of tumor necrosis factor (TNF)-alpha, preventing it from binding to cellular receptors. Infliximab also binds to membranebound TNF-alpha found on inflammatory cell surfaces, inducing apoptosis. Currently, infliximab is used for the induction and maintenance of remission in Crohn's disease (CD), with documented success. Infliximab's efficacy in the treatment of ulcerative colitis (UC) is now being investigated due to the similarities in the pathophysiology of CD and UC.
The aim of this study was to review and evaluate the current literature of infliximab use in steroid-refractory UC to assess its role in treatment.
A search of MEDLINE was conducted (1950-November 2007). Key terms included, but were not limited to, infliximab, inflammatory bowel disease, ulcerative colitis, cost, and quality of life. Studies included for review were limited to English-language, full-text, randomized, double-blind, placebo-controlled trials. Clinical trials were reviewed and summarized.
Four controlled clinical trials of infliximab in the treatment of steroid-refractory UC were found and assessed. In a double-blind, randomized, controlled trial in 43 patients with moderately severe, glucocorticoid-resistant UC, infliximab and placebo were not significantly different with respect to clinical and sigmoidoscopic remission or quality of life 2 and 6 weeks after infliximab treatment. In a multicenter, randomized, double-blind, placebo-controlled study in 45 patients with moderately severe to severe glucocorticoid-resistant UC, infliximab was associated with a significantly reduced need for colectomy compared with placebo (29% vs 67%; P=0.017). The Active Ulcerative Colitis Trials (ACT) 1 and 2 together included 728 patients with moderate to severe glucocorticoid-resistant UC. The primary outcome, the rate of clinical response at 8 weeks, was significantly higher with infliximab compared with placebo (5 mg/kg: ACT 1, 69.4%, ACT 2, 64.5%; 10 mg/kg: ACT 1, 61.5%, ACT 2, 69.2%; placebo: ACT 1, 37.2%;, ACT 2, 29.3%; all, P < 0.001 vs placebo). Based on the data from ACT 1 and 2, infliximab was associated with improved health-related quality-of-life (HRQOL) scores based on the Inflammatory Bowel Disease Questionnaire and the 36-item Short Form Health Survey.
Current data suggest that infliximab is an effective alternative treatment option for patients with moderate to severe UC with an inadequate response to conventional glucocorticoid treatment. Further trials are needed to assess infliximab's impact on the treatment and progression of UC, the HRQL of patients with UC, and the economic impact on the health care system.
英夫利昔单抗是一种嵌合型免疫球蛋白G1κ单克隆抗体，它能以高亲和力和特异性与可溶性肿瘤坏死因子（TNF）-α结合，阻止其与细胞受体结合。英夫利昔单抗还能与炎症细胞表面的膜结合型TNF-α结合，诱导细胞凋亡。目前，英夫利昔单抗已被用于诱导和维持克罗恩病（CD）的缓解，且已有成功的记录。由于CD和溃疡性结肠炎（UC）在病理生理学上存在相似性，目前正在研究英夫利昔单抗治疗UC的疗效。
本研究的目的是回顾和评估目前关于英夫利昔单抗用于激素难治性UC的文献，以评估其在治疗中的作用。
检索了MEDLINE（1950年至2007年11月）。关键词包括但不限于英夫利昔单抗、炎症性肠病、溃疡性结肠炎、成本和生活质量。纳入综述的研究限于英文全文随机双盲安慰剂对照试验。对临床试验进行了回顾和总结。
发现并评估了四项英夫利昔单抗治疗激素难治性UC的对照临床试验。在一项针对43例中度严重糖皮质激素抵抗性UC患者的双盲随机对照试验中，英夫利昔单抗治疗2周和6周后，在临床和乙状结肠镜缓解或生活质量方面，英夫利昔单抗与安慰剂无显著差异。在一项针对45例中度严重至严重糖皮质激素抵抗性UC患者的多中心随机双盲安慰剂对照研究中，与安慰剂相比，英夫利昔单抗显著降低了结肠切除术的需求（29%对67%；P=0.017）。活性溃疡性结肠炎试验（ACT）1和2共纳入728例中度至重度糖皮质激素抵抗性UC患者。主要结局指标，即8周时的临床缓解率，英夫利昔单抗组显著高于安慰剂组（5mg/kg：ACT 1为69.4%，ACT 2为64.5%；10mg/kg：ACT 1为61.5%，ACT 2为69.2%；安慰剂：ACT 1为37.2%，ACT 2为29.3%；所有P值与安慰剂相比均<0.001）。根据ACT 1和2的数据，基于炎症性肠病问卷和36项简短健康调查，英夫利昔单抗与改善健康相关生活质量（HRQOL）评分相关。
目前的数据表明，对于中度至重度UC且对传统糖皮质激素治疗反应不佳的患者，英夫利昔单抗是一种有效的替代治疗选择。需要进一步的试验来评估英夫利昔单抗对UC治疗和病程、UC患者HRQL以及对医疗保健系统的经济影响。
