Keating Gillian M, Perry Caroline M
Adis International Limited, 40 Centorian Drive, PB 65901, Mairangi Bay, Auckland 10, New Zealand.
BioDrugs. 2002;16(2):111-48. doi: 10.2165/00063030-200216020-00005.
Infliximab is a chimeric monoclonal antibody that binds to tumour necrosis factor-alpha (TNFalpha) and neutralises its effects. TNFalpha plays an important role in the development of both Crohn's disease and rheumatoid arthritis. In a large, double-blind, randomised study involving patients with active, refractory Crohn's disease, significantly more recipients of intravenous infliximab, compared with placebo, achieved a clinical response after 4 weeks' follow-up. Moreover, infliximab administration was associated with a rapid improvement in endoscopic and histological findings in clinical trials involving patients with active, refractory Crohn's disease. The results of the A Crohn's Disease Clinical Trial Evaluating Infliximab in a New Long-Term Treatment Regimen (ACCENT) I study showed that maintenance infliximab therapy prolonged response and remission in patients with moderate to severe Crohn's disease. In patients with enterocutaneous fistulae associated with Crohn's disease who were involved in a double-blind, randomised study, significantly more patients who received multiple infusions of infliximab, compared with placebo, experienced a > or=50% reduction from baseline in the number of draining fistulae at > or =2 consecutive study visits. In patients with active rheumatoid arthritis refractory to treatment with methotrexate who were enrolled in a large, double-blind, randomised study [the Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) study], American College of Rheumatology (ACR) 20, 50 and 70% response rates were seen in significantly more patients who received multiple infusions of infliximab plus methotrexate, compared with methotrexate plus placebo, after 30 and 54 weeks' treatment. Moreover, the ACR 20% response rate was maintained after 102 weeks' treatment. In addition, significantly less radiographic progression was seen in infliximab plus methotrexate, compared with methotrexate plus placebo, recipients after 54 weeks' treatment. Infliximab therapy was also associated with improvements in health-related quality of life in patients with Crohn's disease or rheumatoid arthritis. Infliximab was generally well tolerated in clinical trials with the most common adverse events including upper respiratory tract infection, headache, nausea, coughing, sinusitis and diarrhoea. Infliximab therapy may be associated with an increased risk of reactivation of tuberculosis in patients with latent disease. In conclusion, infliximab is an important treatment option in patients with active Crohn's disease who have not responded to conventional therapy and in patients with Crohn's disease who have fistulae. Moreover, infliximab plus methotrexate is effective in patients with active rheumatoid arthritis who have not responded adequately to traditional disease-modifying antirheumatic drugs, in terms of reducing symptoms and signs, improving physical function and delaying the progression of structural damage.
英夫利昔单抗是一种嵌合单克隆抗体，可与肿瘤坏死因子-α（TNFα）结合并中和其作用。TNFα在克罗恩病和类风湿关节炎的发病过程中均起重要作用。在一项针对活动期、难治性克罗恩病患者的大型双盲随机研究中，与安慰剂相比，静脉注射英夫利昔单抗的患者在4周随访后实现临床缓解的比例显著更高。此外，在涉及活动期、难治性克罗恩病患者的临床试验中，英夫利昔单抗治疗与内镜及组织学检查结果的快速改善相关。“评估英夫利昔单抗在新的长期治疗方案中的克罗恩病临床试验（ACCENT）I”研究结果显示，维持英夫利昔单抗治疗可延长中度至重度克罗恩病患者的缓解期。在一项针对克罗恩病相关肠皮肤瘘患者的双盲随机研究中，与安慰剂相比，接受多次英夫利昔单抗输注的患者在连续≥2次研究访视时引流瘘管数量较基线减少≥50%的比例显著更高。在一项大型双盲随机研究[类风湿关节炎联合治疗抗TNF试验（ATTRACT）研究]中纳入的对甲氨蝶呤治疗无效的活动期类风湿关节炎患者中，与甲氨蝶呤加安慰剂相比，接受多次英夫利昔单抗加甲氨蝶呤输注的患者在治疗30周和54周后达到美国风湿病学会（ACR）20%、50%和70%缓解率的比例显著更高。此外，在治疗102周后仍维持ACR 20%的缓解率。此外，在治疗54周后，与甲氨蝶呤加安慰剂相比，英夫利昔单抗加甲氨蝶呤治疗的患者影像学进展明显更少。英夫利昔单抗治疗还与克罗恩病或类风湿关节炎患者健康相关生活质量的改善相关。在临床试验中，英夫利昔单抗总体耐受性良好，最常见的不良事件包括上呼吸道感染、头痛、恶心、咳嗽、鼻窦炎和腹泻。英夫利昔单抗治疗可能会增加潜伏性结核病患者结核病复发的风险。总之，英夫利昔单抗是对传统治疗无反应的活动期克罗恩病患者以及有瘘管的克罗恩病患者的重要治疗选择。此外，英夫利昔单抗加甲氨蝶呤在对传统抗风湿药物反应不佳的活动期类风湿关节炎患者中，在减轻症状和体征、改善身体功能以及延缓结构损伤进展方面有效。
