溃疡性结肠炎的非手术治疗进展
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摘要
溃疡性结肠炎(UC)是一种病因尚不明确,累及直肠和结肠的慢性非特异性肠道炎性疾病。目前UC的常规治疗药物主要有氨基水杨酸、糖皮质激素和免疫抑制剂,当合并严重并发症及癌变时可行手术治疗。随着研究进一步深入,出现了新型治疗方式,主要包括沙利度胺、生物制剂、粪菌移植、选择性白细胞吸附疗法及干细胞疗法等。该文通过综述UC非手术治疗的研究现状,从而为临床上治疗UC提供一定的参考。
Ulcerative colitis(UC) is a chronic nonspecific inflammatory intestinal disease involved with the rectum and colon with an elusive etiology. Currently, the therapeutic drugs of UC mainly include amino salicylic acid, corticosteroids and immunosuppressor. Surgical intervention is considered in those UC patients with severe complications and canceration. Along with the research progression, novel therapeutic technologies of US emerge, such as thalidomide, biological agents, fecal microbiota transplantation, selective leukocytapheresis and stem cells, etc. In this article, the research progress in the non-surgical treatment of UC was summarized, aiming to provide reference for clinical treatment of UC.
Ulcerative colitis(UC) is a chronic nonspecific inflammatory intestinal disease involved with the rectum and colon with an elusive etiology. Currently, the therapeutic drugs of UC mainly include amino salicylic acid, corticosteroids and immunosuppressor. Surgical intervention is considered in those UC patients with severe complications and canceration. Along with the research progression, novel therapeutic technologies of US emerge, such as thalidomide, biological agents, fecal microbiota transplantation, selective leukocytapheresis and stem cells, etc. In this article, the research progress in the non-surgical treatment of UC was summarized, aiming to provide reference for clinical treatment of UC.
引文
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[5]Shah SA, Paradkar M, Desai D, Ashavaid TF. Nucleoside diphosphate-linked moiety X-type motif 15 C415T variant as a predictor for thiopurine-induced toxicity in Indian patients. J Gastroenterol Hepatol,2017,32(3):620-624.
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[10]Christensen B, Gibson P, Micic D, Colman RJ, Goeppinger SR, Kassim O, Yarur A, Weber CR, Cohen RD, Rubin DT.Safety and efficacy of combination treatment with calcineurin inhibitorsandvedolizumabinpatientswithrefractory inflammatory bowel disease. Clin Gastroenterol Hepatol,2018,pii:S1542-3565(18)30466-X.
[11]Escher M, Stange EF, Herrlinger KR. Two cases of fatal Pneumocystis jirovecii, pneumonia as a complication of tacrolimus therapy in ulcerative colitis—a need for prophylaxis.J Crohns Colitis,2010,4(5):606-609.
[12]Ogata H, Kato J, Hirai F, Hida N, Matsui T, Matsumoto T,Koyanagi K, Hibi T. Double-blind, placebo-controlled trial of oral tacrolimus(FK506)in the management of hospitalized patients with steroid-refractory ulcerative colitis. Inflamm Bowel Dis,2012,18(5):803-808.
[13]栾兴龙,苏峰,程元星.长期甲氨蝶呤治疗硫唑嘌呤干预无效型溃疡性结肠炎的临床研究.中华结直肠疾病电子杂志,2018,7(2):141-144.
[14]Herfarth H, Barnes EL, Valentine JF, Hanson J, Higgins PDR, Isaacs KL, Jackson S, Osterman MT, Anton K, Ivanova A, Long MD, Martin C, Sandler RS, Abraham B, Cross RK, Dryden G, Fischer M, Harlan W, Levy C, McCabe R,Polyak S, Saha S, Williams E, Yajnik V, Serrano J, Sands BE, Lewis JD; Clinical Research Alliance of the Crohn’s and Colitis Foundation. Methotrexate is not superior to placebo in maintaining steroid-free response or remission in ulcerative colitis. Gastroenterology, 2018,155(4):1098-1108.
[15]Smith MR, Cooper SC. Mycophenolate mofetil therapy in the management of inflammatory bowel disease—a retrospective case series and review. J Crohns Colitis,2014,8(8):890-897.
[16]Macaluso FS, Maida M, Renna S, Orlando E, Affronti M,Sapienza C, Dimarco M, Orlando R, Rizzuto G, Cottone M,Orlando A. Mycophenolate mofetil is a valid option in patients with inflammatory bowel disease resistant to TNF-αinhibitors and conventional immunosuppressants. Dig Liver Dis,2017,49(2):157-162.
[17]宋岩,杨虎,姜葵,王邦茂.沙利度胺及其类似物治疗炎症性肠病的系统性回顾.临床荟萃,2018,33(5):434-439.
[18]BramuzzoM,VenturaA,MartelossiS,LazzeriniM.Thalidomide for inflammatory bowel disease:systematic review.Medicine(Baltimore),2016,95(30):e4239.
[19]Bariol C, Meagher AP, Vickers CR, Byrnes DJ, Edwards PD,Hing M, Wettstein AR, Field A. Early studies on the safety and efficacy of thalidomide for symptomatic inflammatory bowel disease. J Gastroenterol Hepatol,2002,17(2):135-139.
[20]Danese S. Mechanisms of action of infliximab in inflammatory bowel disease:an anti-inflammatory multitasker. Dig Liver Dis,2008, 40(suppl 2):S225-S228.
[21]李懿璇,李世荣,李俊霞,杨欣艳,王化虹.英夫利昔单抗-类克在激素抵抗及激素依赖溃疡性结肠炎治疗中的应用.世界华人消化杂志,2012,20(21):1987-1992.
[22]Clark M, Colombel JF, Feagan BC, Fedorak RN, Hanauer SB,KammMA,MayerL,RegueiroC,RutgeertsP,Sandborn WJ, Sands BE, Schreiber S, Targan S, Travis S, Vermeire S. American gastroenterological association consensus development conference on the use of biologics in the treatment of inflammatory bowel disease, June 21-23, 2006.Gastroenterology,2007,133(1):312-339.
[23]王诗怡,范一宏,吕宾.炎症性肠病生物治疗的不良反应及防治策略.胃肠病学和肝病学杂志,2015,24(8):1006-1011.
[24]Lemaitre M, Kirchgesner J, Rudnichi A, Carrat F, Zureik M, Carbonnel F, Dray-Spira R. Association between use of thiopurines or tumor necrosis factor antagonists alone or in combination and risk of lymphoma in patients with inflammatory bowel disease. JAMA,2017,318(17):1679-1686.
[25]中华医学会消化病学分会炎症性肠病学组.炎症性肠病诊断与治疗的共识意见(2012年·广州).中华内科杂志,2012,51(10):818-831.
[26]D’Haens GR, Panaccione R, Higgins PD, Vermeire S, GassullM, Chowers Y, Hanauer SB, Herfarth H, Hommes DW, Kamm M, L?fberg R, Quary A, Sands B, Sood A, Watermeyer G,Lashner B, Lémann M, Plevy S, Reinisch W, Schreiber S,Siegel C, Targan S, Watanabe M, Feagan B, Sandborn WJ,Colombel JF, Travis S. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn’s and Colitis Organization:when to start, when to stop, which drug to choose, and how to predict response?Am J Gastroenterol,2011,106(2):199-212.
[27]Rawla P, Sunkara T, Raj JP. Role of biologics and biosimilars in inflammatory bowel disease:current trends and future perspectives. J Inflamm Res,2018,11:215-226.
[28]Park SC, Jeen YT. Anti-integrin therapy for inflammatory bowel disease. World J Gastroenterol,2018,24(17):1868-1880.
[29]李美,苗建壮,许述.炎症性肠病小分子免疫抑制剂的研发进展.药学学报,2018,53(8):1290-1302.
[30]Fiorino G, D’Amico F, Italia A, Gilardi D, Furfaro F, Danese S.JAK inhibitors:novel developments in management of ulcerative colitis. Best Pract Res Clin Gastroenterol,2018,32-33:89-93.
[31]廖诗乐,陈白莉,曾志荣.粪菌移植治疗炎症性肠病的现状和问题.新医学,2014,45(9):569-572.
[32]Rossen NG, Fuentes S, van der Spek MJ, Tijssen JG, Hartman JH, Duflou A, L?wenberg M, van den Brink GR, Mathus-Vliegen EM, de Vos WM, Zoetendal EG, D’Haens GR,Ponsioen CY. Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis.Gastroenterology,2015,149(1):110-118.e4.
[33]Wang S, Xu M, Wang W, Cao X, Piao M, Khan S, Yan F, Cao H, Wang B. Systematic review:adverse events of fecal microbiota transplantation. PLoS One,2016,11(8):e0161174.
[34]Peng Z, Xiang J, He Z, Zhang T, Xu L, Cui B, Li P, Huang G,Ji G, Nie Y, Wu K, Fan D, Zhang F. Colonic transendoscopic enteral tubing:a novel way of transplanting fecal microbiota.Endosc Int Open,2016,4(6):E610-E613.
[35]Lai YM, Yao WY, He Y, Jiang X, Gu YB, Chen MH, Liu YL, Yuan YZ, Qian JM. Adsorptive granulocyte and monocyte apheresis in the treatment of ulcerative colitis:the first multicenter study in China. GutLiver,2017,11(2):216-225.
[36]Markovic BS, Kanjevac T, Harrell CR, Gazdic M, Fellabaum C,Arsenijevic N, Volarevic V. Molecular and cellular mechanisms involved in mesenchymal stem cell-based therapy of inflammatory bowel diseases. Stem Cell Rev,2018,14(2):153-165.
[2]Bermejo F, Lopez-Sanroman A, Taxonera C, Gisbert JP, PérezCalle JL, Vera I, Menchén L, Martín-Arranz MD, Opio V,Carneros JA, Van-Domselaar M, Mendoza JL, Luna M, López P, Calvo M, Algaba A. Acute pancreatitis in inflammatory bowel disease, with special reference to azathioprine-induced pancreatitis. Aliment Pharmacol Ther,2008,28(5):623-628.
[3]Hibi T, Naganuma M, Kitahora T, Kinjyo F, Shimoyama T.Low-dose azathioprine is effective and safe for maintenance of remission in patients with ulcerative colitis. J Gastroenterol,2003,38(8):740-746.
[4]Newman WG, Payne K, Tricker K, Roberts SA, Fargher E,Pushpakom S, Alder JE, Sidgwick GP, Payne D, Elliott RA,Heise M, Elles R, Ramsden SC, Andrews J, Houston JB,Qasim F, Shaffer J, Griffiths CE, Ray DW, Bruce I, Ollier WE; TARGET study recruitment team. A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment:the TARGET study. Pharmacogenomics,2011,12(6):815-826.
[5]Shah SA, Paradkar M, Desai D, Ashavaid TF. Nucleoside diphosphate-linked moiety X-type motif 15 C415T variant as a predictor for thiopurine-induced toxicity in Indian patients. J Gastroenterol Hepatol,2017,32(3):620-624.
[6]Farkas K, Molnár T, Szepes Z. Ability of different rescue therapies to save the bowel in acute, severe, steroid-refractory ulcerative colitis. Expert Rev Gastroenterol Hepatol, 2014, 8(6):695-702.
[7]Sternthal MB, Murphy SJ, George J, Kornbluth A, Lichtiger S, Present DH. Adverse events associated with the use of cyclosporine in patients with inflammatory bowel disease. Am J Gastroenterol,2008,103(4):937-943.
[8]Van Assche G, D’Haens G, Noman M, Vermeire S, Hiele M, Asnong K, Arts J, D’Hoore A, Penninckx F, Rutgeerts P. Randomized, double-blind comparison of 4 mg/kg versus2 mg/kg intravenous cyclosporine in severe ulcerative colitis.Gastroenterology,2003,125(4):1025-1031.
[9]Saifuddin A, Harris A. Tacrolimus therapy in moderate to subacute ulcerative proctocolitis:a large single-centre cohort study. Frontline Gastroenterol,2018,9(2):148-153.
[10]Christensen B, Gibson P, Micic D, Colman RJ, Goeppinger SR, Kassim O, Yarur A, Weber CR, Cohen RD, Rubin DT.Safety and efficacy of combination treatment with calcineurin inhibitorsandvedolizumabinpatientswithrefractory inflammatory bowel disease. Clin Gastroenterol Hepatol,2018,pii:S1542-3565(18)30466-X.
[11]Escher M, Stange EF, Herrlinger KR. Two cases of fatal Pneumocystis jirovecii, pneumonia as a complication of tacrolimus therapy in ulcerative colitis—a need for prophylaxis.J Crohns Colitis,2010,4(5):606-609.
[12]Ogata H, Kato J, Hirai F, Hida N, Matsui T, Matsumoto T,Koyanagi K, Hibi T. Double-blind, placebo-controlled trial of oral tacrolimus(FK506)in the management of hospitalized patients with steroid-refractory ulcerative colitis. Inflamm Bowel Dis,2012,18(5):803-808.
[13]栾兴龙,苏峰,程元星.长期甲氨蝶呤治疗硫唑嘌呤干预无效型溃疡性结肠炎的临床研究.中华结直肠疾病电子杂志,2018,7(2):141-144.
[14]Herfarth H, Barnes EL, Valentine JF, Hanson J, Higgins PDR, Isaacs KL, Jackson S, Osterman MT, Anton K, Ivanova A, Long MD, Martin C, Sandler RS, Abraham B, Cross RK, Dryden G, Fischer M, Harlan W, Levy C, McCabe R,Polyak S, Saha S, Williams E, Yajnik V, Serrano J, Sands BE, Lewis JD; Clinical Research Alliance of the Crohn’s and Colitis Foundation. Methotrexate is not superior to placebo in maintaining steroid-free response or remission in ulcerative colitis. Gastroenterology, 2018,155(4):1098-1108.
[15]Smith MR, Cooper SC. Mycophenolate mofetil therapy in the management of inflammatory bowel disease—a retrospective case series and review. J Crohns Colitis,2014,8(8):890-897.
[16]Macaluso FS, Maida M, Renna S, Orlando E, Affronti M,Sapienza C, Dimarco M, Orlando R, Rizzuto G, Cottone M,Orlando A. Mycophenolate mofetil is a valid option in patients with inflammatory bowel disease resistant to TNF-αinhibitors and conventional immunosuppressants. Dig Liver Dis,2017,49(2):157-162.
[17]宋岩,杨虎,姜葵,王邦茂.沙利度胺及其类似物治疗炎症性肠病的系统性回顾.临床荟萃,2018,33(5):434-439.
[18]BramuzzoM,VenturaA,MartelossiS,LazzeriniM.Thalidomide for inflammatory bowel disease:systematic review.Medicine(Baltimore),2016,95(30):e4239.
[19]Bariol C, Meagher AP, Vickers CR, Byrnes DJ, Edwards PD,Hing M, Wettstein AR, Field A. Early studies on the safety and efficacy of thalidomide for symptomatic inflammatory bowel disease. J Gastroenterol Hepatol,2002,17(2):135-139.
[20]Danese S. Mechanisms of action of infliximab in inflammatory bowel disease:an anti-inflammatory multitasker. Dig Liver Dis,2008, 40(suppl 2):S225-S228.
[21]李懿璇,李世荣,李俊霞,杨欣艳,王化虹.英夫利昔单抗-类克在激素抵抗及激素依赖溃疡性结肠炎治疗中的应用.世界华人消化杂志,2012,20(21):1987-1992.
[22]Clark M, Colombel JF, Feagan BC, Fedorak RN, Hanauer SB,KammMA,MayerL,RegueiroC,RutgeertsP,Sandborn WJ, Sands BE, Schreiber S, Targan S, Travis S, Vermeire S. American gastroenterological association consensus development conference on the use of biologics in the treatment of inflammatory bowel disease, June 21-23, 2006.Gastroenterology,2007,133(1):312-339.
[23]王诗怡,范一宏,吕宾.炎症性肠病生物治疗的不良反应及防治策略.胃肠病学和肝病学杂志,2015,24(8):1006-1011.
[24]Lemaitre M, Kirchgesner J, Rudnichi A, Carrat F, Zureik M, Carbonnel F, Dray-Spira R. Association between use of thiopurines or tumor necrosis factor antagonists alone or in combination and risk of lymphoma in patients with inflammatory bowel disease. JAMA,2017,318(17):1679-1686.
[25]中华医学会消化病学分会炎症性肠病学组.炎症性肠病诊断与治疗的共识意见(2012年·广州).中华内科杂志,2012,51(10):818-831.
[26]D’Haens GR, Panaccione R, Higgins PD, Vermeire S, GassullM, Chowers Y, Hanauer SB, Herfarth H, Hommes DW, Kamm M, L?fberg R, Quary A, Sands B, Sood A, Watermeyer G,Lashner B, Lémann M, Plevy S, Reinisch W, Schreiber S,Siegel C, Targan S, Watanabe M, Feagan B, Sandborn WJ,Colombel JF, Travis S. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn’s and Colitis Organization:when to start, when to stop, which drug to choose, and how to predict response?Am J Gastroenterol,2011,106(2):199-212.
[27]Rawla P, Sunkara T, Raj JP. Role of biologics and biosimilars in inflammatory bowel disease:current trends and future perspectives. J Inflamm Res,2018,11:215-226.
[28]Park SC, Jeen YT. Anti-integrin therapy for inflammatory bowel disease. World J Gastroenterol,2018,24(17):1868-1880.
[29]李美,苗建壮,许述.炎症性肠病小分子免疫抑制剂的研发进展.药学学报,2018,53(8):1290-1302.
[30]Fiorino G, D’Amico F, Italia A, Gilardi D, Furfaro F, Danese S.JAK inhibitors:novel developments in management of ulcerative colitis. Best Pract Res Clin Gastroenterol,2018,32-33:89-93.
[31]廖诗乐,陈白莉,曾志荣.粪菌移植治疗炎症性肠病的现状和问题.新医学,2014,45(9):569-572.
[32]Rossen NG, Fuentes S, van der Spek MJ, Tijssen JG, Hartman JH, Duflou A, L?wenberg M, van den Brink GR, Mathus-Vliegen EM, de Vos WM, Zoetendal EG, D’Haens GR,Ponsioen CY. Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis.Gastroenterology,2015,149(1):110-118.e4.
[33]Wang S, Xu M, Wang W, Cao X, Piao M, Khan S, Yan F, Cao H, Wang B. Systematic review:adverse events of fecal microbiota transplantation. PLoS One,2016,11(8):e0161174.
[34]Peng Z, Xiang J, He Z, Zhang T, Xu L, Cui B, Li P, Huang G,Ji G, Nie Y, Wu K, Fan D, Zhang F. Colonic transendoscopic enteral tubing:a novel way of transplanting fecal microbiota.Endosc Int Open,2016,4(6):E610-E613.
[35]Lai YM, Yao WY, He Y, Jiang X, Gu YB, Chen MH, Liu YL, Yuan YZ, Qian JM. Adsorptive granulocyte and monocyte apheresis in the treatment of ulcerative colitis:the first multicenter study in China. GutLiver,2017,11(2):216-225.
[36]Markovic BS, Kanjevac T, Harrell CR, Gazdic M, Fellabaum C,Arsenijevic N, Volarevic V. Molecular and cellular mechanisms involved in mesenchymal stem cell-based therapy of inflammatory bowel diseases. Stem Cell Rev,2018,14(2):153-165.