生物制剂治疗炎症性肠病的进展
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摘要
近年来,随着炎症性肠病的病因和发病机制方面研究取得了重大进展,生物制剂的应用使其病情进展和疾病转归得到了新转折。抗肿瘤坏死因子α已成为治疗中重度炎症性肠病的一线用药。近年来,抗黏附因子也成为治疗炎症性肠病的重要药物,维多珠单抗(Vedolizumab)常被用于抗肿瘤坏死因子α失应答和对其他治疗方法不耐受的情况。而更多的生物制剂正处于临床试验的各个开发阶段,包括抗IL-12/23的乌司奴单抗(Ustekinumab)、JAK抑制剂—托法替尼(Tofacitinib)和抗黏附分子—Etrolizumab。本文主要介绍目前新出现的主要的治疗炎症性肠病的生物制剂的有效性和安全性。
In recent years,there is great progress in understanding the etiology and pathogenesis of inflammatory bowel disease(IBD).The application of biological agents has brought about a new turning point in treatment of IBD.Anti-TNF-alpha has become the first-line drug in the treatment of moderate to severe inflammatory bowel disease.Anti-adhesion factor has also become an important drug in the treatment of inflammatory bowel disease in recent years.Vedolizumab is often used for anti-TNF-alpha no-response and other treatment intolerance.More biological agents are being developed at various stages of clinical trials,including ustekinumab which belongs to anti-IL-12/23,tofacitinib,a JAK inhibitor,and etrolizumab,an anti-adhesion molecule.We review the effectiveness and safety of major biological agents in IBD.
In recent years,there is great progress in understanding the etiology and pathogenesis of inflammatory bowel disease(IBD).The application of biological agents has brought about a new turning point in treatment of IBD.Anti-TNF-alpha has become the first-line drug in the treatment of moderate to severe inflammatory bowel disease.Anti-adhesion factor has also become an important drug in the treatment of inflammatory bowel disease in recent years.Vedolizumab is often used for anti-TNF-alpha no-response and other treatment intolerance.More biological agents are being developed at various stages of clinical trials,including ustekinumab which belongs to anti-IL-12/23,tofacitinib,a JAK inhibitor,and etrolizumab,an anti-adhesion molecule.We review the effectiveness and safety of major biological agents in IBD.
引文
[1] Burger D,Travis S.Conventional medical management of inflammatory bowel disease[J].Gastroenterology,2011,140(6):1827-1837.
[2] Rutgeerts P,Sandborn WJ,Feagan BG,et al.Infliximab for induction and maintenance therapy for ulcerative colitis[J].N Engl J Med,2005,353(23):2462-2476.
[3] Feagan BG,Panaccione R,Sandborn WJ,et al.Effects of adalimumab therapy on incidence of hospitalization and surgery in Crohn's disease:results from the CHARM study[J].Gastroenterology,2008,135(5):1493-1499.
[4] Danese S,Furfaro F,Vetrano S.Targeting S1P in inflammatory bowel disease:new avenues for modulating intestinal leukocyte migration[J].J Crohns Colitis,2018,12(suppl_2):S678-S686.
[5] Wendling D,Prati C.Paradoxical effects of anti-TNF-alpha agents in inflammatory diseases[J].Expert Rev Clin Immunol,2014,10(1):159-169.
[6] Lichtenstein GR,Rutgeerts P,Sandborn WJ,et al.A pooled analysis of infections,malignancy,and mortality in infliximab- and immunomodulator-treated adult patients with inflammatory bowel disease[J].Am J Gastroenterol,2012,107(7):1051-1063.
[7] D′Haens GR,Panaccione R,Higgins PD,et al.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[J].Am J Gastroenterol,2011,106(2):199-212.
[8] Taks M,Pijls PA,Derijks LJ,et al.Short article:the effect of implementation of a treatment algorithm for infliximab on remission rates and drug costs in inflammatory bowel disease patients[J].Eur J Gastroenterol Hepatol,2017,29(2):169-173.
[9] Bots SJ,Kuin S,Ponsioen CY,et al.Relapse rates and predictors for relapse in a real-life cohort of IBD patients after discontinuation of anti-TNF therapy[J].Scand J Gastroenterol,2019,54(3):281-288.
[10] Inokuchi T,Takahashi S,Hiraoka S,et al.Long-term outcomes of patients with Crohn's disease who received infliximab or adalimumab as the first-line biologics[J].J Gastroenterol Hepatol,2019 .[Epub ahead of print]
[11] Sandborn WJ,Feagan BG,Marano C,et al.Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis[J].Gastroenterology,2014,146(1):85-95.
[12] Sandborn WJ,Feagan BG,Marano C,et al.Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis[J].Gastroenterology,2014,146(1):96-109.
[13] Zhang D,Xiong B,Li X,et al.Meta-analysis:serious adverse events in Crohn's disease patients treated with TNF-alpha inhibitors[J].Hepatogastroenterology,2013,60(126):1333-1342.
[14] Lobaton T,Vermeire S,Van Assche G,et al.Review article:anti-adhesion therapies for inflammatory bowel disease[J].Aliment Pharmacol Ther,2014,39(6):579-594.
[15] Amiot A,Peyrin-Biroulet L.Current,new and future biological agents on the horizon for the treatment of inflammatory bowel diseases[J].Therap Adv Gastroenterol,2015,8(2):66-82.
[16] Yousry TA,Major EO,Ryschkewitsch C,et al.Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy[J].N Engl J Med,2006,354(9):924-933.
[17] Danese S,Panes J.Development of drugs to target interactions between leukocytes and endothelial cells and treatment algorithms for inflammatory bowel diseases[J].Gastroenterology,2014,147(5):981-989.
[18] Feagan BG,Rutgeerts P,Sands BE,et al.Vedolizumab as induction and maintenance therapy for ulcerative colitis[J].N Engl J Med,2013,369(8):699-710.
[19] Arijs I,De Hertogh G,Lemmens B,et al.Effect of vedolizumab (anti-alpha4beta7-integrin) therapy on histological healing and mucosal gene expression in patients with UC[J].Gut,2018,67(1):43-52.
[20] Feagan BG,Rubin DT,Danese S,et al.Efficacy of vedolizumab induction and maintenance therapy in patients with uicerative colitis,regardless of prior exposure to tumor necrosis factor antagonists[J].Clin Gastroenterol Hepatol,2017,15(2):229-239.
[21] Sandborn WJ,Feagan BG,Rutgeerts P,et al.Vedolizumab as induction and maintenance therapy for Crohn's disease[J].N Engl J Med,2013,369(8):711-721.
[22] Feagan BG,Schwartz D,Danese S,et al.Efficacy of vedolizumab in fistulising crohn′s disease:exploratory analyses of data from GEMINI 2[J].J Crohns Colitis,2018,12(5):621-626.
[23] Vermeire S,O'Byrne S,Keir M,et al.Etrolizumab as induction therapy for ulcerative colitis:a randomised,controlled,phase 2 trial[J].Lancet,2014,384(9940):309-318.
[24] Motaghi E,Ghasemi-Pirbaluti M,Zabihi M.Etrolizumab versus infliximab in the treatment of induction phase of ulcerative colitis:a systematic review and indirect comparison[J].Pharmacol Res,2019,139:120-125.
[25] Vignali DA,Kuchroo VK.IL-12 family cytokines:immunological playmakers[J].Nat Immunol,2012,13(8):722-728.
[26] Rawla P,Sunkara T,Raj JP.Role of biologics and biosimilars in inflammatory bowel disease:current trends and future perspectives[J].J Inflamm Res,2018,11:215-226.
[27] Leonardi CL,Kimball AB,Papp KA,et al.Efficacy and safety of ustekinumab,a human interleukin-12/23 monoclonal antibody,in patients with psoriasis:76-week results from a randomised,double-blind,placebo-controlled trial (Phoenix 1) [J].Lancet,2008,371(9625):1665-1674.
[28] Feagan BG,Sandborn WJ,Gasink C,et al.Ustekinumab as induction and maintenance therapy for crohn′s disease[J].N Engl J Med,2016,375(20):1946-1960.
[29] Sandborn WJ,Gasink C,Gao LL,et al.Ustekinumab induction and maintenance therapy in refractory Crohn's disease[J].N Engl J Med,2012,367(16):1519-1528.
[30] Macaluso FS,Orlando A,Cottone M.Anti-interleukin-12 and anti-interleukin-23 agents in Crohn′s disease[J].Expert Opin Biol Ther,2018.[Epub ahead of print]
[31] Janssen Research & Development.A study to evaluate the safety and efficacy of ustekinumab induction and maintenance therapy in participants with moderately to severely active ulcerative colitis (UNIFI) [EB/OL].[2018-4-30].https://clinicaltrials.gov/ct2/show/NCT02407236 term=ustekinumab & cond=ulcerative+colitis & rank=1.
[32] Allocca M,Furfaro F,Fiorino G,et al.Can IL-23 be a good target for ulcerative colitis[J].Best Pract Res Clin Gastroenterol,2018,32-33:95-102.
[33] Sandborn WJ,Ghosh S,Panes J,et al.Tofacitinib,an oral Janus kinase inhibitor,in active ulcerative colitis[J].N Engl J Med,2012,367(7):616-624.
[34] Dai C,Jiang M,Sun MJ.Tofacitinib as induction and maintenance therapy for ulcerative colitis[J].N Engl J Med,2017,377(5):496.
[35] Sandborn WJ,Ghosh S,Panes J,et al.A phase 2 study of tofacitinib,an oral Janus kinase inhibitor,in patients with Crohn's disease[J].Clin Gastroenterol Hepatol,2014,12(9):1485-1493.
[36] Panes J,Sandborn WJ,Schreiber S,et al.Tofacitinib for induction and maintenance therapy of Crohn′s disease:results of two phase IIb randomised placebo-controlled trials[J].Gut,2017,66(6):1049-1059.
[2] Rutgeerts P,Sandborn WJ,Feagan BG,et al.Infliximab for induction and maintenance therapy for ulcerative colitis[J].N Engl J Med,2005,353(23):2462-2476.
[3] Feagan BG,Panaccione R,Sandborn WJ,et al.Effects of adalimumab therapy on incidence of hospitalization and surgery in Crohn's disease:results from the CHARM study[J].Gastroenterology,2008,135(5):1493-1499.
[4] Danese S,Furfaro F,Vetrano S.Targeting S1P in inflammatory bowel disease:new avenues for modulating intestinal leukocyte migration[J].J Crohns Colitis,2018,12(suppl_2):S678-S686.
[5] Wendling D,Prati C.Paradoxical effects of anti-TNF-alpha agents in inflammatory diseases[J].Expert Rev Clin Immunol,2014,10(1):159-169.
[6] Lichtenstein GR,Rutgeerts P,Sandborn WJ,et al.A pooled analysis of infections,malignancy,and mortality in infliximab- and immunomodulator-treated adult patients with inflammatory bowel disease[J].Am J Gastroenterol,2012,107(7):1051-1063.
[7] D′Haens GR,Panaccione R,Higgins PD,et al.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[J].Am J Gastroenterol,2011,106(2):199-212.
[8] Taks M,Pijls PA,Derijks LJ,et al.Short article:the effect of implementation of a treatment algorithm for infliximab on remission rates and drug costs in inflammatory bowel disease patients[J].Eur J Gastroenterol Hepatol,2017,29(2):169-173.
[9] Bots SJ,Kuin S,Ponsioen CY,et al.Relapse rates and predictors for relapse in a real-life cohort of IBD patients after discontinuation of anti-TNF therapy[J].Scand J Gastroenterol,2019,54(3):281-288.
[10] Inokuchi T,Takahashi S,Hiraoka S,et al.Long-term outcomes of patients with Crohn's disease who received infliximab or adalimumab as the first-line biologics[J].J Gastroenterol Hepatol,2019 .[Epub ahead of print]
[11] Sandborn WJ,Feagan BG,Marano C,et al.Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis[J].Gastroenterology,2014,146(1):85-95.
[12] Sandborn WJ,Feagan BG,Marano C,et al.Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis[J].Gastroenterology,2014,146(1):96-109.
[13] Zhang D,Xiong B,Li X,et al.Meta-analysis:serious adverse events in Crohn's disease patients treated with TNF-alpha inhibitors[J].Hepatogastroenterology,2013,60(126):1333-1342.
[14] Lobaton T,Vermeire S,Van Assche G,et al.Review article:anti-adhesion therapies for inflammatory bowel disease[J].Aliment Pharmacol Ther,2014,39(6):579-594.
[15] Amiot A,Peyrin-Biroulet L.Current,new and future biological agents on the horizon for the treatment of inflammatory bowel diseases[J].Therap Adv Gastroenterol,2015,8(2):66-82.
[16] Yousry TA,Major EO,Ryschkewitsch C,et al.Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy[J].N Engl J Med,2006,354(9):924-933.
[17] Danese S,Panes J.Development of drugs to target interactions between leukocytes and endothelial cells and treatment algorithms for inflammatory bowel diseases[J].Gastroenterology,2014,147(5):981-989.
[18] Feagan BG,Rutgeerts P,Sands BE,et al.Vedolizumab as induction and maintenance therapy for ulcerative colitis[J].N Engl J Med,2013,369(8):699-710.
[19] Arijs I,De Hertogh G,Lemmens B,et al.Effect of vedolizumab (anti-alpha4beta7-integrin) therapy on histological healing and mucosal gene expression in patients with UC[J].Gut,2018,67(1):43-52.
[20] Feagan BG,Rubin DT,Danese S,et al.Efficacy of vedolizumab induction and maintenance therapy in patients with uicerative colitis,regardless of prior exposure to tumor necrosis factor antagonists[J].Clin Gastroenterol Hepatol,2017,15(2):229-239.
[21] Sandborn WJ,Feagan BG,Rutgeerts P,et al.Vedolizumab as induction and maintenance therapy for Crohn's disease[J].N Engl J Med,2013,369(8):711-721.
[22] Feagan BG,Schwartz D,Danese S,et al.Efficacy of vedolizumab in fistulising crohn′s disease:exploratory analyses of data from GEMINI 2[J].J Crohns Colitis,2018,12(5):621-626.
[23] Vermeire S,O'Byrne S,Keir M,et al.Etrolizumab as induction therapy for ulcerative colitis:a randomised,controlled,phase 2 trial[J].Lancet,2014,384(9940):309-318.
[24] Motaghi E,Ghasemi-Pirbaluti M,Zabihi M.Etrolizumab versus infliximab in the treatment of induction phase of ulcerative colitis:a systematic review and indirect comparison[J].Pharmacol Res,2019,139:120-125.
[25] Vignali DA,Kuchroo VK.IL-12 family cytokines:immunological playmakers[J].Nat Immunol,2012,13(8):722-728.
[26] Rawla P,Sunkara T,Raj JP.Role of biologics and biosimilars in inflammatory bowel disease:current trends and future perspectives[J].J Inflamm Res,2018,11:215-226.
[27] Leonardi CL,Kimball AB,Papp KA,et al.Efficacy and safety of ustekinumab,a human interleukin-12/23 monoclonal antibody,in patients with psoriasis:76-week results from a randomised,double-blind,placebo-controlled trial (Phoenix 1) [J].Lancet,2008,371(9625):1665-1674.
[28] Feagan BG,Sandborn WJ,Gasink C,et al.Ustekinumab as induction and maintenance therapy for crohn′s disease[J].N Engl J Med,2016,375(20):1946-1960.
[29] Sandborn WJ,Gasink C,Gao LL,et al.Ustekinumab induction and maintenance therapy in refractory Crohn's disease[J].N Engl J Med,2012,367(16):1519-1528.
[30] Macaluso FS,Orlando A,Cottone M.Anti-interleukin-12 and anti-interleukin-23 agents in Crohn′s disease[J].Expert Opin Biol Ther,2018.[Epub ahead of print]
[31] Janssen Research & Development.A study to evaluate the safety and efficacy of ustekinumab induction and maintenance therapy in participants with moderately to severely active ulcerative colitis (UNIFI) [EB/OL].[2018-4-30].https://clinicaltrials.gov/ct2/show/NCT02407236 term=ustekinumab & cond=ulcerative+colitis & rank=1.
[32] Allocca M,Furfaro F,Fiorino G,et al.Can IL-23 be a good target for ulcerative colitis[J].Best Pract Res Clin Gastroenterol,2018,32-33:95-102.
[33] Sandborn WJ,Ghosh S,Panes J,et al.Tofacitinib,an oral Janus kinase inhibitor,in active ulcerative colitis[J].N Engl J Med,2012,367(7):616-624.
[34] Dai C,Jiang M,Sun MJ.Tofacitinib as induction and maintenance therapy for ulcerative colitis[J].N Engl J Med,2017,377(5):496.
[35] Sandborn WJ,Ghosh S,Panes J,et al.A phase 2 study of tofacitinib,an oral Janus kinase inhibitor,in patients with Crohn's disease[J].Clin Gastroenterol Hepatol,2014,12(9):1485-1493.
[36] Panes J,Sandborn WJ,Schreiber S,et al.Tofacitinib for induction and maintenance therapy of Crohn′s disease:results of two phase IIb randomised placebo-controlled trials[J].Gut,2017,66(6):1049-1059.