Mahdi G, Israel D M, Hassall E
Division of Gastroenterology, British Columbia Children's Hospital, Vancouver, Canada.
Am J Gastroenterol. 1996 Jul;91(7):1355-9.
This prospective, open trial of treatment was conducted to determine whether cyclosporine A (CSA) is effective in inducing remission in children with severe, active Crohn's colitis refractory to other medical treatment and if remission may be maintained by 6-mercaptopurine (6-MP) and 5-aminosalicylic acid (5-ASA) after discontinuing CSA.
Ten children (five males, five females), ages 1.2-16 yr (mean 11), all had failed to respond to 4 wk of treatment with i.v. methylprednisolone and total parenteral nutrition/elemental diet; three were already receiving 6-mercaptopurine. CSA was initially given as a twice daily i.v. dosage and was switched to oral CSA when a clinical response was observed. At the same time, corticosteroids were switched to the oral route and tapered over the next 3 months. Patients were grouped by treatment outcome. "Responders" were those who achieved remission with i.v. CSA therapy, "relapsers" were those who achieved remission with i.v. CSA but relapsed later, and nonresponders had not achieved remission after 4 wk of i.v. CSA. Responders were given 6-MP with intent to discontinue CSA after 6 months and maintain remission by 6-MP and 5-ASA.
There were seven responders to CSA. For all patients, the Pediatric Crohn's Disease Activity Index (PCDAI) (score range 0-100) had a mean value of 55 (range 40-65) just before treatment; PCDAI improved to a mean of 19 (range 5-42.5) after 2 wk of CSA therapy. Four of the seven responders discontinued CSA after 6 months and remain well on 6-MP and 5ASA alone for 22, 13, 8, and 3 months. One patient had massive GI bleeding (from active Crohn's colitis), which stopped within 48 h of CSA treatment. There were three relapsers (at 2-6 months of CSA), and three were nonresponders. Three patients who were already receiving 6-MP before CSA therapy either did not respond to CSA or relapsed while receiving it. The six nonresponders and relapsers required surgical resection. Transient side effects included hypertension responding to nifedipine in one child and hirsutism and tremors in another.
We conclude that CSA offers a good remission rate for children with severe Crohn's colitis failing other medical treatment, although relapse was common especially if the child was already on 6-MP. In addition, CSA may offer "temporizing" therapy in severe, active Crohn's colitis; this may allow surgery to be performed electively, with time for psychosocial and nutritional preparation before surgery.
开展这项前瞻性、开放性治疗试验，以确定环孢素A（CSA）对其他药物治疗无效的重度活动性克罗恩病结肠炎患儿诱导缓解是否有效，以及停用CSA后6-巯基嘌呤（6-MP）和5-氨基水杨酸（5-ASA）能否维持缓解状态。
10名儿童（5名男性，5名女性），年龄1.2 - 16岁（平均11岁），均对静脉注射甲泼尼龙及全胃肠外营养/要素饮食4周的治疗无反应；3名患儿已在接受6-巯基嘌呤治疗。CSA最初静脉注射，每日2次，观察到临床反应后改为口服CSA。同时，糖皮质激素改为口服给药，并在接下来3个月逐渐减量。根据治疗结果对患者进行分组。“缓解者”是指静脉注射CSA治疗后实现缓解的患儿，“复发者”是指静脉注射CSA治疗后实现缓解但后来复发的患儿，“无反应者”是指静脉注射CSA 4周后未实现缓解的患儿。缓解者给予6-MP，计划在6个月后停用CSA，并通过6-MP和5-ASA维持缓解。
7名患儿对CSA治疗有反应。所有患者在治疗前小儿克罗恩病活动指数（PCDAI）（评分范围0 - 100）的平均值为55（范围40 - 65）；CSA治疗2周后，PCDAI平均值改善至19（范围5 - 42.5）。7名缓解者中有4名在6个月后停用CSA，仅使用6-MP和5-ASA分别维持良好状态22、13、8和3个月。1名患儿出现大量胃肠道出血（源于活动性克罗恩病结肠炎），在CSA治疗48小时内出血停止。有3名复发者（在CSA治疗2 - 6个月时复发），3名无反应者。3名在CSA治疗前已接受6-MP治疗的患儿对CSA治疗无反应或在接受治疗时复发。6名无反应者和复发者需要手术切除。短暂的副作用包括1名儿童出现对硝苯地平有反应的高血压，另1名儿童出现多毛症和震颤。
我们得出结论，对于其他药物治疗无效的重度克罗恩病结肠炎患儿，CSA有较好的缓解率，尽管复发很常见，尤其是患儿已在使用6-MP时。此外，CSA可能为重度活动性克罗恩病结肠炎提供“临时”治疗；这可能使手术能够择期进行，有时间在手术前进行心理社会和营养方面的准备。
