Division of Gastroenterology, University of California San Diego, La Jolla, CA 92093-0063, USA.
Gut. 2011 Dec;60(12):1754-63. doi: 10.1136/gutjnl-2011-300934. Epub 2011 Oct 13.
Crohn's disease is a chronic inflammatory disorder that follows a progressive and destructive course. Ultimately, uncontrolled inflammation leads to bowel damage from disease-related complications such as strictures, fistulas and abscesses and surgical resection. Conventional 'step-care', whereby corticosteroids and immunosuppressives are prescribed sequentially, is an incremental approach to treatment that does not prevent disease progression and conveys an important risk of adverse events from repeated courses of corticosteroids. Although the immunosuppressives azathioprine, 6-mercaptopurine and methotrexate are corticosteroid-sparing, they are not highly effective for inducing mucosal healing or preventing disease progression. Tumour necrosis factor antagonists induce and maintain mucosal healing and reduce surgery and hospitalisation rates. This holds out the possibility that long-term use of these agents may prevent bowel damage. Combination therapy with immunosuppressives and tumour necrosis factor antagonists is likely the best strategy for achieving optimal outcomes in patients at high risk of disease progression. However, accurate prognostic markers must be identified to guide patient selection. Long-term prospective studies with robust outcomes are still needed to establish definitively the efficacy and safety of early combination therapy to prevent bowel damage, loss of gastrointestinal tract function and permanent disability.
克罗恩病是一种慢性炎症性疾病，呈进行性和破坏性发展。最终，不受控制的炎症会导致肠道受损，出现与疾病相关的并发症，如狭窄、瘘管和脓肿，并需要进行手术切除。传统的“逐步治疗”方法是按顺序开具皮质类固醇和免疫抑制剂，这是一种渐进式的治疗方法，无法预防疾病进展，并存在因反复使用皮质类固醇而导致不良事件的重要风险。虽然免疫抑制剂如硫唑嘌呤、巯嘌呤和甲氨蝶呤可减少皮质类固醇的使用，但它们对于诱导黏膜愈合或预防疾病进展的效果并不显著。肿瘤坏死因子拮抗剂可诱导并维持黏膜愈合，并降低手术和住院率。这表明长期使用这些药物可能预防肠道损伤。免疫抑制剂和肿瘤坏死因子拮抗剂联合治疗可能是实现高疾病进展风险患者最佳治疗效果的最佳策略。然而，必须确定准确的预后标志物来指导患者选择。仍需要进行长期前瞻性研究，以明确早期联合治疗预防肠道损伤、胃肠道功能丧失和永久性残疾的疗效和安全性。
