炎症性肠病患者缓解期药物降级策略

doi:10.16138/j.1673-6087.2025.02.01

摘要/Abstract

摘要：

炎症性肠病（inflammatory bowel disease，IBD）包括溃疡性结肠炎（ulcerative colitis，UC）和克罗恩病（Crohn disease，CD），需长期药物维持缓解。制定缓解期药物降级策略对减少不良反应、减轻经济负担具有重要意义，但停药风险和获益尚存争议。部分缓解期UC患者可减量使用5-氨基水杨酸盐，但停药后复发风险升高。免疫调节剂如硫唑嘌呤长期使用存在安全性问题，但通过药物监测体系可实现安全停药。生物制剂在缓解期停药后复发率较高，特别是未达到深度缓解者。此外，联合治疗患者的药物降级策略需综合评估。停药后的复发监测尤为关键，内镜、血清C反应蛋白和粪便钙卫蛋白等生物标志物可作为有效的预测工具。本文通过回顾缓解期IBD患者药物降级研究，为临床实践提供参考，促进医患共同决策。

关键词: 炎症性肠病, 药物降级, 缓解期, 复发监测

Abstract:

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn disease (CD), requires long-term medication to maintain remission. Developing a medicine de-escalation strategies during remission is crucial for reducing side effects and alleviating economic burdens, but the risks and benefits of medicine discontinuation remain controversial. The dose of 5-aminosalicylic acid (5-ASA) can be reduced in partial UC patients during remission, but the risk of relapse increases after medicine discontinuation. Long-term use of immunomodulators such as azathioprine has safety issues, but safe discontinuation of the medicine can be achieved through a medicine monitoring systems. The relapse rate after discontinuation of biologics agents during remission is high, especially in patients who have not achieved deep remission. The medicine de-escalation strategy for patient receiving combination therapy requires comprehensive assessment. Relapse monitoring after medicine discontinuation is critical, endoscopy and biomarkers such as C-reactive protein (CRP) and fecal calprotectin (FCP) can be used as effective predictive tools. This review summarizes recent studies on medicine de-escalation in IBD remission to provide reference for clinical practice and promote shared decision-making between patients and physicians.

Key words: Inflammatory bowel disease, Medicine de-escalation, Remission period, Recurrence monitoring

中图分类号:

R574

顾于蓓, 洪聿. 炎症性肠病患者缓解期药物降级策略[J]. 内科理论与实践, 2025, 20(02): 101-106.

GU Yubei, HONG Yu. Medicine de-escalation strategies in inflammatory bowel disease for remission maintenance[J]. Journal of Internal Medicine Concepts & Practice, 2025, 20(02): 101-106.

图/表 1

参考文献 44

[1]	Doherty G, Katsanos KH, Burisch J, et al. European Crohn’s and Colitis organisation topical review on treatment withdrawal ['exit strategies'] in inflammatory bowel disease[J]. J Crohns Colitis, 2018, 12(1): 17-31. doi: 10.1093/ecco-jcc/jjx101 pmid: 28981623
[2]	Subramanian CR, Triadafilopoulos G. Care of inflammatory bowel disease patients in remission[J]. Gastroenterol Rep (Oxf), 2016, 4(4): 261-271.
[3]	Best WR, Becktel JM, Singleton JW, et al. Development of a Crohn’s disease activity index[J]. Gastroenterology, 1976, 70(3):439-444. pmid: 1248701
[4]	Harvey RF, Bradshaw JM. A simple index of Crohn’s-disease activity[J]. Lancet, 1980, 1(8167): 514. doi: 10.1016/s0140-6736(80)92767-1 pmid: 6102236
[5]	van Staa TP, Card T, Logan RF, et al. 5-aminosalicylate use and colorectal cancer risk in inflammatory bowel disease: a large epidemiological study[J]. Gut, 2005, 54(11):1573-1578. doi: 10.1136/gut.2005.070896 pmid: 15994215
[6]	Moss JG, Parry CM, Holt RCL, et al. 5-ASA induced interstitial nephritis in patients with inflammatory bowel disease: a systematic review[J]. Eur J Med Res, 2022, 27(1): 61. doi: 10.1186/s40001-022-00687-y pmid: 35488310
[7]	D’arienzo A, Panarese A, D’armiento FP, et al. 5-aminosalicylic acid suppositories in the maintenance of remission in idiopathic proctitis or proctosigmoiditis: a double-blind placebo-controlled clinical trial[J]. Am J Gastroenterol, 1990, 85(9): 1079-1082. pmid: 2202199
[8]	Hanauer S, Good LI, Goodman MW, et al. Long-term use of mesalamine (Rowasa) suppositories in remission maintenance of ulcerative proctitis[J]. Am J Gastroenterol, 2000, 95(7): 1749-1754. pmid: 10925979
[9]	Ardizzone S, Petrillo M, Imbesi V, et al. Is maintenance therapy always necessary for patients with ulcerative colitis in remission?[J]. Aliment Pharmacol Ther, 1999, 13(3): 373-379.
[10]	ANON. An oral preparation of mesalamine as long-term maintenance therapy for ulcerative colitis[J]. Ann Intern Med, 1996, 124(2): 204-211.
[11]	Sandberg-Gertzén H, Järnerot G, Kraaz W. Azodisal sodium in the treatment of ulcerative colitis[J]. Gastroenterology, 1986, 90(4): 1024-1030. pmid: 2868964
[12]	Ran Z, Wu K, Matsuoka K, et al. Asian Organization for Crohn’s and Colitis and Asia Pacific Association of Gastroenterology practice recommendations for medical management and monitoring of inflammatory bowel disease in Asia[J]. J Gastroenterol Hepatol, 2021, 36(3): 637-645.
[13]	Khan N, Abbas AM, Koleva YN, et al. Long-term mesalamine maintenance in ulcerative colitis[J]. Inflamm Bowel Dis, 2013, 19(6): 1123-1129.
[14]	Pica R, Cassieri C, Cocco A, et al. A randomized trial comparing 4.8 vs. 2.4 g/day of oral mesalazine for maintenance of remission in ulcerative colitis[J]. Dig Liver Dis, 2015, 47(11): 933-937.
[15]	Paoluzi OA, Iacopini F, Pica R, et al. Comparison of two different daily dosages (2.4 vs. 1.2 g) of oral mesalazine in maintenance of remission in ulcerative colitis patients: 1-year follow-up study[J]. Aliment Pharmacol Ther, 2005, 21(9): 1111-1119.
[16]	Chapman TP, Frias Gomes C, Louis E, et al. Review article:withdrawal of 5-aminosalicylates in inflammatory bowel disease[J]. Aliment Pharmacol Ther, 2020, 52(1): 73-84.
[17]	吴开春, 梁洁, 冉志华, 等. 炎症性肠病诊断与治疗的共识意见(2018年·北京)[J]. 中国实用内科杂志, 2018, 38(9): 796-813.
[18]	Beaugerie L, Brousse N, Bouvier AM, et al. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study[J]. Lancet, 2009, 374(9701): 1617-1625. doi: 10.1016/S0140-6736(09)61302-7 pmid: 19837455
[19]	Peyrin-Biroulet L, Khosrotehrani K, Carrat F, et al. Increased risk for nonmelanoma skin cancers in patients who receive thiopurines for inflammatory bowel disease[J]. Gastroenterology, 2011, 141(5): 1621-1628. doi: 10.1053/j.gastro.2011.06.050 pmid: 21708105
[20]	Lopez A, Mounier M, Bouvier AM, et al. Increased risk of acute myeloid leukemias and myelodysplastic syndromes in patients who received thiopurine treatment for inflammatory bowel disease[J]. Clin Gastroenterol Hepatol, 2014, 12(8): 1324-1329.
[21]	Bourrier A, Carrat F, Colombel JF, et al. Excess risk of urinary tract cancers in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study[J]. Aliment Pharmacol Ther, 2016, 43(2): 252-261.
[22]	Lemann M, Mary JY, Colombel JF, et al. A randomized, double-blind, controlled withdrawal trial in Crohn’s disease patients in long-term remission on azathioprine[J]. Gastroenterology, 2005, 128(7): 1812-1818.
[23]	Cassinotti A, Actis GC, Duca P, et al. Maintenance treatment with azathioprine in ulcerative colitis: outcome and predictive factors after drug withdrawal[J]. Am J Gastroenterol, 2009, 104(11): 2760-2767. doi: 10.1038/ajg.2009.410 pmid: 19623172
[24]	Torres J, Boyapati RK, Kennedy NA, et al. Systematic review of effects of withdrawal of immunomodulators or biologic agents from patients qith inflammatory bowel disease[J]. Gastroenterology, 2015, 149(7): 1716-1730. doi: 10.1053/j.gastro.2015.08.055 pmid: 26381892
[25]	Feuerstein JD, Isaacs KL, Schneider Y, et al. AGA clinical practice guidelines on the management of moderate to severe ulcerative Colitis[J]. Gastroenterology, 2020, 158(5): 1450-1461. doi: S0016-5085(20)30018-4 pmid: 31945371
[26]	Panaccione R, Steinhart AH, Bressler B, et al. Canadian association of gastroenterology clinical practice guideline for the management of luminal Crohn’s disease[J]. Clin Gastroenterol Hepatol, 2019, 17(9): 1680-1713.
[27]	Little DHW, Tabatabavakili S, Shaffer SR, et al. Effectiveness of dose de-escalation of biologic therapy in inflammatory bowel disease:a systematic review[J]. Am J Gastroenterol, 2020, 115(11): 1768-1774.
[28]	Noor NM, Sousa P, Bettenworth D, et al. ECCO topical review on biological treatment cycles in Crohn’s disease[J]. J Crohns Colitis, 2023, 17(7): 1031-1045.
[29]	Louis E, Mary JY, Vernier-Massouille G, et al. Maintenance of remission among patients with Crohn's disease on antimetabolite therapy after infliximab therapy is stopped[J]. Gastroenterology, 2012, 142(1): 63-70. doi: 10.1053/j.gastro.2011.09.034 pmid: 21945953
[30]	Pauwels RWM, van der Woude CJ, Nieboer D, et al. Prediction of relapse after anti-tumor necrosis factor cessation in Crohn’s disease:individual participant data meta-analysis of 1 317 patients from 14 studies[J]. Clin Gastroenterol Hepatol, 2022, 20(8): 1671-1686.
[31]	Kobayashi T, Motoya S, Nakamura S, et al. Discontinuation of infliximab in patients with ulcerative colitis in remission (HAYABUSA):a multicentre, open-label, randomised controlled trial[J]. Lancet Gastroenterol Hepatol, 2021, 6(6): 429-437.
[32]	Louis E, Resche-Rigon M, Laharie D, et al. Withdrawal of infliximab or concomitant immunosuppressant therapy in patients with Crohn’s disease on combination therapy (SPARE): a multicentre, open-label, randomised controlled trial[J]. Lancet Gastroenterol Hepatol, 2023, 8(3):215-227.
[33]	Martin A, Nachury M, Peyrin-Biroulet L, et al. Maintenance of remission among patients with inflammatory bowel disease after vedolizumab discontinuation:a multicentre cohort study[J]. J Crohns Colitis, 2020, 14(7): 896-903.
[34]	Miyatani Y, Kobayashi T. De-escalation of therapy in patients with quiescent inflammatory bowel disease[J]. Gut Liver, 2023, 17(2): 181-189.
[35]	Baert F, Moortgat L, Van Assche G, et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn’s disease[J]. Gastroenterology, 2010, 138(2): 463-468.
[36]	Zenlea T, Yee EU, Rosenberg L, et al. Histology grade is independently associated with relapse risk in patients with ulcerative Colitis in clinical remission:a prospective study[J]. Am J Gastroenterol, 2016, 111(5): 685-690. doi: 10.1038/ajg.2016.50 pmid: 26977756
[37]	Kennedy NA, Kalla R, Warner B, et al. Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease: relapse and recapture rates, with predictive factors in 237 patients[J]. Aliment Pharmacol Ther, 2014, 40(11-12): 1313-1323.
[38]	Langhorst J, Boone J, Lauche R, et al. Faecal lactoferrin, calprotectin, PMN-elastase, CRP, and white blood cell count as indicators for mucosal healing and clinical course of disease in patients with mild to moderate ulcerative Colitis:post hoc analysis of a prospective clinical trial[J]. J Crohns Colitis, 2016, 10(7):786-794. doi: 10.1093/ecco-jcc/jjw044 pmid: 26874351
[39]	Kopylov U, Rosenfeld G, Bressler B, et al. Clinical utility of fecal biomarkers for the diagnosis and management of inflammatory bowel disease[J]. Inflamm Bowel Dis, 2014, 20(4): 742-756. doi: 10.1097/01.MIB.0000442681.85545.31 pmid: 24562174
[40]	D’haens G, Ferrante M, Vermeire S, et al. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease[J]. Inflamm Bowel Dis, 2012, 18(12): 2218-2224. doi: 10.1002/ibd.22917 pmid: 22344983
[41]	Molander P, Färkkilä M, Ristimäki A, et al. Does fecal calprotectin predict short-term relapse after stopping TNFα-blocking agents in inflammatory bowel disease patients in deep remission?[J]. J Crohns Colitis, 2015, 9(1):33-40. doi: 10.1016/j.crohns.2014.06.012 pmid: 25052347
[42]	Buisson A, Mak WY, Andersen MJ, et al. Faecal calprotectin is a very reliable tool to predict and monitor the risk of relapse after therapeutic de-escalation in patients with inflammatory bowel diseases[J]. J Crohns Colitis, 2019, 13(8): 1012-1024. doi: 10.1093/ecco-jcc/jjz023 pmid: 30726887
[43]	Ben-Horin S, Chowers Y, Ungar B, et al. Undetectable anti-TNF drug levels in patients with long-term remission predict successful drug withdrawal[J]. Aliment Pharmacol Ther, 2015, 42(3): 356-364.
[44]	Rajca S, Grondin V, Louis E, et al. Alterations in the intestinal microbiome (dysbiosis) as a predictor of relapse after infliximab withdrawal in Crohn’s disease[J]. Inflamm Bowel Dis, 2014, 20(6): 978-986.