Feagan Brian G, Sandborn William J
Robart's Research Institute, University of Western Ontario, London, Ontario, Canada.
Rev Gastroenterol Disord. 2002;2 Suppl 2:S9-15.
The initial choice of therapy for mild to moderately active Crohn's disease is controversial. Both the National Cooperative Crohn's Disease Study (NCCDS) and the European Cooperative Crohn's Disease Study (ECCDS) demonstrated that sulfasalazine is effective for the induction of remission. Subsequent studies of new mesalamine formulations showed inconsistent results; two trials, however, demonstrated a statistically significant improvement with Pentasa and Asacol treatment, and meta-analyses suggest a modest benefit of mesalamine maintenance therapy. The NCCDS and ECCDS trials found that corticosteroid therapy is much more effective than sulfasalazine for induction of remission, but corticosteroids did not show maintenance benefits. Corticosteroid use is frequently associated with adverse effects, and the majority of patients treated with prednisone become either steroid-refractory or steroid-dependent; many of these patients ultimately need treatment with immunosuppressives and/or surgery. Budesonide, a topical corticosteroid with high first-pass hepatic metabolism, is slightly less effective in inducing remission than conventional corticosteroids but is significantly less likely to cause side effects. Budesonide 9 mg/day was shown to be more effective than mesalamine (Pentasa 4 g/day) for induction therapy, but budesonide has been ineffective as a maintenance therapy. Mesalamine may be useful for patients with more extensive disease, those intolerant of sulfasalazine, or those with contraindications or intolerance to budesonide. Alternatively, sulfasalazine is effective in the presence of colonic disease. Clinicians must decide on the basis of the existing evidence whether budesonide or mesalamine is the preferred initial therapy for active Crohn's disease.
轻至中度活动性克罗恩病的初始治疗选择存在争议。美国国家合作克罗恩病研究(NCCDS)和欧洲合作克罗恩病研究(ECCDS)均表明柳氮磺吡啶对诱导缓解有效。随后对新型美沙拉嗪制剂的研究结果并不一致;然而,两项试验显示使用颇得斯安和艾迪莎治疗有统计学意义的显著改善,荟萃分析提示美沙拉嗪维持治疗有一定益处。NCCDS和ECCDS试验发现,皮质类固醇疗法在诱导缓解方面比柳氮磺吡啶有效得多,但皮质类固醇未显示出维持治疗的益处。使用皮质类固醇常伴有不良反应,大多数接受泼尼松治疗的患者会出现激素抵抗或激素依赖;这些患者中的许多最终需要免疫抑制剂和/或手术治疗。布地奈德是一种首过肝代谢率高的局部皮质类固醇,在诱导缓解方面比传统皮质类固醇稍差,但引起副作用的可能性显著降低。已表明布地奈德9毫克/天在诱导治疗方面比美沙拉嗪(颇得斯安4克/天)更有效,但布地奈德作为维持治疗无效。美沙拉嗪可能对病变范围更广、不耐受柳氮磺吡啶或对布地奈德有禁忌证或不耐受的患者有用。或者,柳氮磺吡啶对结肠疾病有效。临床医生必须根据现有证据决定布地奈德或美沙拉嗪是否为活动性克罗恩病的首选初始治疗药物。