Schröder Oliver, Blumenstein Irina, Stein Jürgen
First Department of Internal Medicine, ZAFES, Johann Wolfgang Goethe University, Frankfurt, Germany.
Eur J Gastroenterol Hepatol. 2006 Jan;18(1):11-6. doi: 10.1097/00042737-200601000-00003.
Immunosuppression of chronic active Crohn's disease resistant or intolerant to purine antimetabolites still remains a clinical challenge. To obtain long-lasting effects with the anti-TNF-alpha antibody infliximab repeated infusions are often required. Methotrexate has been shown to be a moderately effective drug in maintaining remission in Crohn's disease. The aim of the present pilot study was to evaluate the combination of infliximab and methotrexate as therapy for refractory Crohn's disease.
Nineteen patients with chronic active Crohn's disease resistant or intolerant to azathioprine were enrolled. Patients received either two infusions of infliximab (5 mg/kg) alone (n=8) or in combination with long-term methotrexate at a dosage of 20 mg/week (n=11) over 48 weeks.
Two out of eight patients receiving infliximab monotherapy and four out of 11 patients treated with infliximab and concomitant methotrexate had discontinued study treatment by week 48, solely because of lack of efficacy. Clinical remission at week 48 was observed in five out of seven patients treated with infliximab and methotrexate, but only in two out of six patients receiving infliximab monotherapy. In addition, patients treated with concomitant methotrexate achieved remission earlier (median time 2 versus 18 weeks) and needed fewer steroids (median prednisolone dose 0 versus 11.8 mg). Despite an increased mean number of adverse events per patient in the methotrexate group, the proportions of patients experiencing any adverse events and serious adverse events were similar across treatment groups.
The combination of infliximab with long-term methotrexate may be a promising concept in refractory Crohn's disease. Our data prompt larger trials.
对嘌呤抗代谢物耐药或不耐受的慢性活动性克罗恩病的免疫抑制仍是一项临床挑战。为了获得抗TNF-α抗体英夫利昔单抗的持久疗效，通常需要重复输注。甲氨蝶呤已被证明是一种在维持克罗恩病缓解方面中等有效的药物。本初步研究的目的是评估英夫利昔单抗和甲氨蝶呤联合治疗难治性克罗恩病的效果。
招募了19例对硫唑嘌呤耐药或不耐受的慢性活动性克罗恩病患者。患者在48周内接受单独两次英夫利昔单抗输注（5mg/kg）（n = 8）或与每周20mg的长期甲氨蝶呤联合使用（n = 11）。
到第48周时，8例接受英夫利昔单抗单药治疗的患者中有2例、11例接受英夫利昔单抗与甲氨蝶呤联合治疗的患者中有4例因缺乏疗效而停止研究治疗。在接受英夫利昔单抗和甲氨蝶呤治疗的7例患者中，有5例在第48周达到临床缓解，但接受英夫利昔单抗单药治疗的6例患者中只有2例达到临床缓解。此外，联合甲氨蝶呤治疗的患者缓解更早（中位时间2周对18周），且所需类固醇更少（中位泼尼松龙剂量0mg对11.8mg）。尽管甲氨蝶呤组患者平均不良事件数量增加，但各治疗组发生任何不良事件和严重不良事件的患者比例相似。
英夫利昔单抗与长期甲氨蝶呤联合使用可能是难治性克罗恩病的一个有前景的治疗方案。我们的数据促使开展更大规模的试验。
