Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Dig Endosc. 2010 Oct;22(4):289-96. doi: 10.1111/j.1443-1661.2010.01009.x.
Azathioprine (AZA) and mercaptopurine (6-MP) are established as effective therapeutic drugs for the induction and maintenance of remission in patients with ulcerative colitis (UC). However, AZA is often intolerable due to adverse effects. Evidence regarding the approach of switching from AZA to 6-MP in patients of Asian ethnicity is lacking. We assessed the tolerability and usefulness of 6-MP in Japanese UC patients who had shown intolerance to AZA.
One-hundred and ten UC patients who had been treated with AZA and/or 6-MP from January 1985 to October 2008 were examined retrospectively.
Among 110 patients, 107 were treated first with AZA; only three were treated first with 6-MP. Thirty-five (33%) of the 107 patients were intolerant of AZA, with adverse effects including myelosuppression (8/35, 23%), hepatotoxicity (8/35, 23%), and abdominal symptoms (6/35, 17%). Among 35 AZA-intolerant patients, 23 were switched to 6-MP treatment. The cumulative probability of colectomy was significantly higher in patients not treated with 6-MP than in patients treated with 6-MP (log-rank test, P =0.0002). Among the 26 patients (23 AZA-intolerant and three AZA-untreated) treated with 6-MP, 22 (85%) could tolerate the therapy. Adverse effects due to 6-MP were abdominal symptoms (2/4), myelosuppression (1/4), and rash (1/4). The median initial dose of 6-MP was 20 mg/day, and the median final dose was 30 mg/day.
6-MP was tolerated in 83% of AZA-intolerant patients, and it was effective for maintenance therapy of UC patients. 6-MP treatment should be considered in AZA-intolerant patients.
巯嘌呤(6-MP)和硫唑嘌呤(AZA)已被证实为溃疡性结肠炎(UC)诱导缓解和维持缓解的有效治疗药物。然而,由于不良反应,AZA 往往难以耐受。关于亚洲人群从 AZA 转换为 6-MP 的方法,目前尚缺乏相关证据。我们评估了对 AZA 不耐受的日本 UC 患者使用 6-MP 的耐受性和有效性。
我们回顾性分析了 1985 年 1 月至 2008 年 10 月期间使用 AZA 和/或 6-MP 治疗的 110 例 UC 患者。
110 例患者中,107 例首先使用 AZA 治疗,仅 3 例首先使用 6-MP 治疗。107 例患者中有 35 例(33%)对 AZA 不耐受,不良反应包括骨髓抑制(8/35,23%)、肝毒性(8/35,23%)和腹部症状(6/35,17%)。35 例 AZA 不耐受的患者中有 23 例转换为 6-MP 治疗。未接受 6-MP 治疗的患者与接受 6-MP 治疗的患者相比,结肠切除术的累积概率显著更高(对数秩检验,P=0.0002)。在接受 6-MP 治疗的 26 例患者(23 例 AZA 不耐受和 3 例 AZA 未治疗)中,22 例(85%)能够耐受该治疗。6-MP 相关不良反应包括腹部症状(2/4)、骨髓抑制(1/4)和皮疹(1/4)。6-MP 的初始剂量中位数为 20mg/天,最终剂量中位数为 30mg/天。
83%的 AZA 不耐受患者能够耐受 6-MP,且 6-MP 对 UC 患者的维持治疗有效。对于 AZA 不耐受的患者,应考虑使用 6-MP 治疗。