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炎症性肠病患者停用硫嘌呤后的复发率。

Relapse rates after withdrawal of thiopurines in patients with inflammatory bowel disease.

机构信息

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, 3rd Floor, Teaching Block, Ansar Nagar, New Delhi, 110029, India.

Department of Radio Diagnosis, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Int J Colorectal Dis. 2022 Aug;37(8):1817-1826. doi: 10.1007/s00384-022-04216-5. Epub 2022 Jul 14.


DOI:10.1007/s00384-022-04216-5
PMID:35835862
Abstract

PURPOSE: Withdrawal of thiopurines after remission is associated with an increased risk of relapse in patients with inflammatory bowel disease (IBD). However, long-term data on thiopurine withdrawal is limited, especially from developing countries where the cost of long-term therapy poses a significant burden on patients. METHODS: Patients with IBD on thiopurine monotherapy for ≥ 4 months, who stopped thiopurines while in clinical remission and were not on any other immunomodulator or biologics at the time of withdrawal, were included in this retrospective analysis. RESULTS: Among 1093 patients with IBD on thiopurine monotherapy, 461 patients stopped thiopurine due to various reasons. Among these, 218 (ulcerative colitis (UC) = 179; Crohn's disease (CD) = 39) patients were in clinical remission and were continued on mesalamine. Overall, 36.7% (n = 80) relapsed after a median duration of 20 months (IQR: 9-49). Relapse rate was higher in UC than CD (39.7% vs 23%, p = 0.055). Cumulative probabilities of relapse were 17%, 34%, and 44% at the end of 1, 3, and 5 years, respectively. The relapse rate at 5 years was significantly lower in patients who had stopped azathioprine after 4 years of therapy (31% vs 54%, p = 0.007). On multi-variate cox regression analysis, male sex [HR: 1.6(1.0-2.6), p = 0.02] and short duration of therapy with thiopurines [HR: 1.02 (1.01-1.02), p = 0.004] before withdrawal were associated with increased risk of relapse. CONCLUSION: Approximately 50% patients with IBD in remission would relapse after 5 years of thiopurine withdrawal. Male sex and shorter treatment duration predict relapse. Treatment should be continued in patients who tolerate and maintain remission on long-term thiopurine.

摘要

目的:缓解后停用硫嘌呤会增加炎症性肠病(IBD)患者复发的风险。然而,关于硫嘌呤停药的长期数据有限,特别是在发展中国家,长期治疗的费用给患者带来了巨大的负担。

方法:本回顾性分析纳入了正在接受硫嘌呤单药治疗≥4 个月、在临床缓解期停用硫嘌呤且在停药时未使用任何其他免疫调节剂或生物制剂的 IBD 患者。

结果:在 1093 例接受硫嘌呤单药治疗的 IBD 患者中,461 例因各种原因停用硫嘌呤。其中,218 例(溃疡性结肠炎(UC)=179 例;克罗恩病(CD)=39 例)患者处于临床缓解期,并继续使用美沙拉嗪。总体而言,中位随访 20 个月(IQR:9-49)后有 36.7%(n=80)复发。UC 的复发率高于 CD(39.7%比 23%,p=0.055)。在 1、3 和 5 年时,累积复发率分别为 17%、34%和 44%。在治疗 4 年后停用硫嘌呤嘧啶的患者,5 年时的复发率显著降低(31%比 54%,p=0.007)。多变量 Cox 回归分析显示,男性[HR:1.6(1.0-2.6),p=0.02]和硫嘌呤治疗时间短[HR:1.02(1.01-1.02),p=0.004]与复发风险增加相关。

结论:约 50%的缓解期 IBD 患者在停用硫嘌呤 5 年后会复发。男性和较短的治疗时间预示着复发。对于能耐受并维持长期硫嘌呤治疗缓解的患者,应继续治疗。

相似文献

[1]
Relapse rates after withdrawal of thiopurines in patients with inflammatory bowel disease.

Int J Colorectal Dis. 2022-8

[2]
Poor Drug Sustainability in Inflammatory Bowel Disease Patients in Clinical Remission on Thiopurine Monotherapy.

Dig Dis Sci. 2021-5

[3]
Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease: relapse and recapture rates, with predictive factors in 237 patients.

Aliment Pharmacol Ther. 2014-12

[4]
Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn's disease: long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresource.

Gut. 2021-4

[5]
Minimal risk of lymphoma and non-melanoma skin cancer despite long-term use of thiopurines in patients with inflammatory bowel disease: A longitudinal cohort analysis from northern India.

J Gastroenterol Hepatol. 2022-8

[6]
Do Thiopurines Reduce the Risk of Surgery in Elderly Onset Inflammatory Bowel Disease? A 20-Year National Population-Based Cohort Study.

Inflamm Bowel Dis. 2017-4

[7]
Thiopurines Have Sustained Long-term Effectiveness in Patients with Inflammatory Bowel Disease, Which is Independent of Disease Duration at Initiation: A Propensity Score Matched Analysis.

J Crohns Colitis. 2024-2-26

[8]
Thiopurine Monotherapy Is Effective in Maintenance of Mild-Moderate Inflammatory Bowel Disease.

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[9]
Complete Endoscopic Healing Is Associated With Lower Relapse Risk After Anti-TNF Withdrawal in Inflammatory Bowel Disease.

Clin Gastroenterol Hepatol. 2023-3

[10]
Azathioprine monotherapy withdrawal in inflammatory bowel diseases: A retrospective mono-centric study.

World J Gastroenterol. 2023-7-21

引用本文的文献

[1]
Precision medicine and drug optimization in adult inflammatory bowel disease patients.

Therap Adv Gastroenterol. 2023-5-10

[2]
Personalized medicine to implementation science: Thiopurines set for the leap.

JGH Open. 2022-10-17

本文引用的文献

[1]
Noninvasive Monitoring After Azathioprine Withdrawal in Patients With Inflammatory Bowel Disease in Deep Remission.

Clin Gastroenterol Hepatol. 2021-11

[2]
The four epidemiological stages in the global evolution of inflammatory bowel disease.

Nat Rev Gastroenterol Hepatol. 2021-1

[3]
Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn's disease: long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresource.

Gut. 2021-4

[4]
Thiopurine monotherapy has a limited place in treatment of patients with mild-to-moderate Crohn's disease.

Gut. 2021-7

[5]
Risk of skin cancers in thiopurines-treated and thiopurines-untreated patients with inflammatory bowel disease: A systematic review and meta-analysis.

J Gastroenterol Hepatol. 2018-11-22

[6]
Low dose of azathioprine is effective to induce and maintain remission in active Crohn disease: A prospective observational study.

Medicine (Baltimore). 2018-8

[7]
Epidemiology of Inflammatory Bowel Disease in India: The Great Shift East.

Inflamm Intest Dis. 2017-11

[8]
European Crohn's and Colitis Organisation Topical Review on Treatment Withdrawal ['Exit Strategies'] in Inflammatory Bowel Disease.

J Crohns Colitis. 2018-1-5

[9]
Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis.

N Engl J Med. 2017-5-4

[10]
3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn's Disease 2016: Part 1: Diagnosis and Medical Management.

J Crohns Colitis. 2016-9-22

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