Fellermann K, Ludwig D, Stahl M, David-Walek T, Stange E F
Department of Internal Medicine I, University of Lübeck, Germany.
Am J Gastroenterol. 1998 Oct;93(10):1860-6. doi: 10.1111/j.1572-0241.1998.539_g.x.
Steroid treatment failure in acute Crohn's disease and ulcerative colitis frequently necessitates surgical intervention. Several alternative therapeutic strategies have been raised. The most promising so far has been intravenous cyclosporine, but the results in the long term have been discouraging. We assessed the efficacy and safety of the new macrolide immunomodulator tacrolimus as an alternative to cyclosporine A.
Eleven patients with steroid-refractory disease (six ulcerative colitis, two indeterminate colitis, two Crohn's disease, one pouchitis) and severe activity according to the Truelove and Witts criteria or Crohn's disease activity index > 150, respectively, were eligible for the study. All patients were treated with intravenous tacrolimus for 7-10 days followed by oral treatment over a median period of 7 months (range 0.25-16). Azathioprine and mesalamine were given concomitantly. Steroids were tapered according to clinical activity.
Seven of 11 patients achieved remission rapidly, whereas a modest improvement was noted in two. Only two patients required an early and one a delayed colectomy. Moreover, a rectovaginal fistula closure in a case of Crohn's disease and an improvement of pouchitis was observed. A tapering to low dose steroids was possible during oral tacrolimus therapy in all nine responders and remission was maintained in five of them (mean follow-up 9.2 months). The drug was well tolerated and side effects were managed conservatively.
Tacrolimus induced rapid remission in steroid resistant inflammatory bowel disease in the majority of cases. It appears to be an effective treatment modality that may be superior to cyclosporine with respect to maintenance of remission.
急性克罗恩病和溃疡性结肠炎患者若出现类固醇治疗失败，往往需要进行手术干预。目前已提出了几种替代治疗策略。迄今为止，最有前景的是静脉注射环孢素，但长期效果并不理想。我们评估了新型大环内酯类免疫调节剂他克莫司作为环孢素A替代药物的疗效和安全性。
11例类固醇难治性疾病患者（6例溃疡性结肠炎、2例未定型结肠炎、2例克罗恩病、1例储袋炎）符合研究条件，分别根据Truelove和Witts标准或克罗恩病活动指数>150判定为病情严重活跃。所有患者先接受静脉注射他克莫司治疗7 - 10天，随后口服治疗，中位治疗期为7个月（范围0.25 - 16个月）。同时给予硫唑嘌呤和美沙拉嗪。根据临床活动情况逐渐减少类固醇用量。
11例患者中有7例迅速实现缓解，2例有一定程度改善。仅2例患者需要早期行结肠切除术，1例需要延迟行结肠切除术。此外，观察到1例克罗恩病患者的直肠阴道瘘闭合，以及储袋炎有所改善。在所有9例病情缓解者口服他克莫司治疗期间，均有可能逐渐减至低剂量类固醇，其中5例维持缓解（平均随访9.2个月）。该药物耐受性良好，副作用通过保守方法处理。
他克莫司在大多数病例中可使类固醇抵抗的炎症性肠病迅速缓解。它似乎是一种有效的治疗方式，在维持缓解方面可能优于环孢素。
