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严格克罗恩病中单用硫嘌呤类药物治疗:来自中低收入国家的真实经验。

Monotherapy with thiopurines in stricturing Crohn's disease: A real-life experience from low- and middle-income countries.

机构信息

Department of Gastroenterology, All India Institute of Medical Sciences, Room No 3093, 3rd Floor, Main Emergency Building, New Delhi, 110 029, India.

Department of Radiology, All India Institute of Medical Sciences, New Delhi, 110 029, India.

出版信息

Indian J Gastroenterol. 2022 Aug;41(4):343-351. doi: 10.1007/s12664-022-01258-z. Epub 2022 Aug 23.

Abstract

BACKGROUND

Stricturing Crohn's disease (CD) is difficult to manage medically with limited treatment options, anti-tumor necrosis factor (TNF) therapy being the first-line therapy. Although thiopurines are also recommended first-line treatment option for maintenance of remission in steroid-dependent CD, evidence on their use in stricturing CD is lacking. We evaluated the efficacy of azathioprine (AZA) in patients with stricturing CD.

METHODS

In this retrospective cohort study (January 2005 to July 2020), patients with stricturing CD who were managed with AZA as a primary therapy for at least 6 months, and had a follow-up of at least 6 months after AZA initiation were included. Disease characteristics, complications, long-term response, and adverse events were noted.

RESULTS

One hundred and fifteen patients were included (mean age 33.8±14 years, 67.8% males, median disease duration 98 months [IQR: 60-158], median follow-up duration 60 months [IQR: 50-96]). 46.1% (n=53) patients had significant anemia at presentation, and 73% (n=84) had isolated small bowel involvement. Median dose of AZA was 100 mg (equivalent to 1.5 mg/kg). Median therapy and follow-up duration (after AZA initiation) was 17 (IQR: 9-42) and 33 months (IQR 18-60), respectively. The cumulative probability of maintaining response without treatment failure at 1, 2, and 5 years was 73.1%, 40.7%, and 18.5%, respectively. Among patients with AZA failure, 15.6% received methotrexate, 13% received anti-TNFs, and 9.5% underwent surgery. Significant anemia (<10 g/dL) at presentation and steroid dependence predicted AZA failure. 31.3% patients experienced adverse events, commonest being leukopenia (n=29, 25.2%).

CONCLUSION

Azathioprine demonstrated good short-term and modest long-term response rates in patients with stricturing CD.

摘要

背景

狭窄型克罗恩病(CD)的治疗较为困难,药物治疗选择有限,抗肿瘤坏死因子(TNF)治疗是一线治疗方法。虽然硫唑嘌呤也被推荐为 CD 患者激素依赖缓解期的一线治疗选择,但在狭窄型 CD 中使用硫唑嘌呤的证据不足。我们评估了硫唑嘌呤(AZA)在狭窄型 CD 患者中的疗效。

方法

在这项回顾性队列研究(2005 年 1 月至 2020 年 7 月)中,纳入了至少接受 AZA 作为一线治疗至少 6 个月,且在 AZA 起始后至少随访 6 个月的狭窄型 CD 患者。记录疾病特征、并发症、长期应答和不良事件。

结果

共纳入 115 例患者(平均年龄 33.8±14 岁,67.8%为男性,中位疾病病程 98 个月[IQR:60-158],中位随访时间 60 个月[IQR:50-96])。46.1%(n=53)患者就诊时存在显著贫血,73%(n=84)患者存在孤立性小肠受累。AZA 的中位剂量为 100 mg(相当于 1.5 mg/kg)。AZA 治疗和随访时间(自 AZA 起始后)的中位数分别为 17(IQR:9-42)和 33 个月(IQR 18-60)。1、2、5 年无治疗失败维持应答的累积概率分别为 73.1%、40.7%和 18.5%。在 AZA 治疗失败的患者中,15.6%接受了甲氨蝶呤,13%接受了抗 TNF 治疗,9.5%接受了手术。就诊时存在显著贫血(<10 g/dL)和激素依赖是 AZA 治疗失败的预测因素。31.3%的患者出现不良事件,最常见的是白细胞减少症(n=29,25.2%)。

结论

在狭窄型 CD 患者中,硫唑嘌呤显示出良好的短期和适度的长期应答率。

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