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General Review Article

‘Treat to Target’ in Mild to Moderate Ulcerative Colitis: Evidence to Support this Strategy

Author(s): Arianna Dal Buono, Giulia Roda, Marjorie Argollo, Kristine Paridaens, Laurent Peyrin-Biroulet and Silvio Danese*

Volume 22, Issue 1, 2021

Published on: 27 July, 2020

Page: [117 - 125] Pages: 9

DOI: 10.2174/1389450121666200727120305

Price: $65

Abstract

Background: The management of chronic conditions, above all rheumatic disease and diabetes, now incorporates a "treat to target" strategy where treatment aims to achieve objective outcomes. This is applicable in ulcerative colitis (UC) as well. Targets are demonstrated to prevent endorgan dysfunction, specifically bowel damage and its complications, and lastly colorectal cancer. Recently, the scientific community has tried to define further targets beyond those currently recommended, namely mucosal healing and clinical remission. Studies that prospectively investigated this approach in UC are scanty and a treat-to-target (T2T) algorithm is not routinely used in daily clinical practice.

Objective: We aim to review current evidence on T2T in UC and discuss its adoption in routine clinical practice as well as in clinical trials.

Methods: A PubMed search was conducted in February 2020 to identify published papers investigating targets’ achievement rates in UC.

Results: Different targets can be achieved through approved drugs for mild to moderate UC; histological remission is emerging as a robust target with respect to long-term outcomes.

Conclusion: Further studies to compare a T2T strategy with the traditional care are needed, particularly in the mild to moderate spectrum of disease.

Keywords: Ulcerative colitis, histological healing, mucosal healing, inflammation, target, remission.

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Graphical Abstract

[1]
Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF. Ulcerative colitis. Lancet 2017; 389(10080): 1756-70.
[http://dx.doi.org/10.1016/S0140-6736(16)32126-2] [PMID: 27914657]
[2]
Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Selecting therapeutic targets in inflammatory bowel disease (STRIDE): Determining therapeutic goals for treat-to-target. Am J Gastroenterol 2015; 110(9): 1324-38.
[http://dx.doi.org/10.1038/ajg.2015.233] [PMID: 26303131]
[3]
Colombel JF, Narula N, Peyrin-Biroulet L. Management strategies to improve outcomes of patients with inflammatory bowel diseases. Gastroenterology 2017; 152(2): 351-361.e5.
[http://dx.doi.org/10.1053/j.gastro.2016.09.046] [PMID: 27720840]
[4]
Colombel JF, Keir ME, Scherl A, et al. Discrepancies between patient-reported outcomes, and endoscopic and histological appearance in UC. Gut 2017; 66(12): 2063-8.
[http://dx.doi.org/10.1136/gutjnl-2016-312307] [PMID: 27590995]
[5]
Römkens TEH, Kranenburg P, Tilburg AV, et al. Assessment of histological remission in ulcerative colitis: discrepancies between daily practice and expert opinion. J Crohn’s Colitis 2018; 12(4): 425-31.
[http://dx.doi.org/10.1093/ecco-jcc/jjx165] [PMID: 29240880]
[6]
Colombel JF, Shin A, Gibson PR. AGA Clinical Practice Update on functional gastrointestinal symptoms in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2019; 17(3): 380-390.e1.
[http://dx.doi.org/10.1016/j.cgh.2018.08.001] [PMID: 30099108]
[7]
Colombel JF, Panaccione R, Bossuyt P, et al. Effect of tight control management on Crohn’s disease (CALM): a multicentre, randomised, controlled phase 3 trial. Lancet 2018; 390(10114): 2779-89.
[http://dx.doi.org/10.1016/S0140-6736(17)32641-7] [PMID: 29096949]
[8]
Magro F, Gionchetti P, Eliakim R, et al. European Crohn’s and Colitis Organisation [ECCO European Crohn’s and Colitis Organisation [ECCO Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders. J Crohn’s Colitis 2017; 11(6): 649-70.
[http://dx.doi.org/10.1093/ecco-jcc/jjx008] [PMID: 28158501]
[9]
Shah SC, Colombel JF, Sands BE, Narula N. Mucosal healing is associated with improved long-term outcomes of patients with ulcerative colitis: A systematic review and meta-analysis. Clin Gastroenterol Hepatol 2016; 14(9): 1245-1255.e8.
[http://dx.doi.org/10.1016/j.cgh.2016.01.015] [PMID: 26829025]
[10]
Ungaro R, Colombel JF, Lissoos T, Peyrin-Biroulet L. A Treat-to-Target Update in Ulcerative Colitis: A Systematic Review. Am J Gastroenterol 2019; 114(6): 874-83.
[http://dx.doi.org/10.14309/ajg.0000000000000183] [PMID: 30908297]
[11]
Lopez A, Pouillon L, Beaugerie L, Danese S, Peyrin-Biroulet L. Colorectal cancer prevention in patients with ulcerative colitis. Best Pract Res Clin Gastroenterol 2018; 32-33: 103-9.
[http://dx.doi.org/10.1016/j.bpg.2018.05.010] [PMID: 30060933]
[12]
Danese S, Roda G, Peyrin-Biroulet L. Evolving therapeutic goals in ulcerative colitis: towards disease clearance. Nat Rev Gastroenterol Hepatol 2020; 17(1): 1-2.
[http://dx.doi.org/10.1038/s41575-019-0211-1] [PMID: 31520081]
[13]
Strober BE, van der Walt JM, Armstrong AW, et al. Clinical goals and barriers to effective psoriasis care. Dermatol Ther (Heidelb) 2019; 9(1): 5-18.
[http://dx.doi.org/10.1007/s13555-018-0279-5] [PMID: 30578464]
[14]
Danve A, Deodhar A. Treat to target in axial spondyloarthritis: What are the issues? Curr Rheumatol Rep 2017; 19(5): 22.
[http://dx.doi.org/10.1007/s11926-017-0648-6] [PMID: 28386759]
[15]
Nardone OM, Cannatelli R, Zardo D, Ghosh S, Iacucci M. Can advanced endoscopic techniques for assessment of mucosal inflammation and healing approximate histology in inflammatory bowel disease? Therap Adv Gastroenterol 2019.121756284819863015
[http://dx.doi.org/10.1177/1756284819863015] [PMID: 31360224]
[16]
Agrawal M, Colombel JF. Treat-to-target in inflammatory bowel diseases: what is the target and how do we treat? Gastrointest Endosc Clin N Am 2019; 29(3): 421-36.
[http://dx.doi.org/10.1016/j.giec.2019.02.004] [PMID: 31078245]
[17]
Colombel JF, D’Haens G, Lee WJ, et al. Outcomes and strategies to support a treat-to-target approach in inflammatory bowel disease: A systematic review. J Crohn’s Colitis 2019.1-13.
[18]
Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol. 19(Suppl A): 5A- 36°
[19]
Fumery M, Singh S, Dulai PS, Gower-Rousseau C, Peyrin-Biroulet L, Sandborn WJ. Natural History of Adult Ulcerative Colitis in Population-based Cohorts: A Systematic Review. Clin Gastroenterol Hepatol 2018; 16(3): 343-356.e3.
[http://dx.doi.org/10.1016/j.cgh.2017.06.016] [PMID: 28625817]
[20]
Lichtenstein GR, Kamm MA, Boddu P, et al. Effect of once- or twice-daily MMX mesalamine (SPD476) for the induction of remission of mild to moderately active ulcerative colitis. Clin Gastroenterol Hepatol 2007; 5(1): 95-102.
[http://dx.doi.org/10.1016/j.cgh.2006.10.025] [PMID: 17234558]
[21]
Lichtenstein GR, Kamm MA, Sandborn WJ, Lyne A, Joseph RE. MMX mesalazine for the induction of remission of mild-to-moderately active ulcerative colitis: efficacy and tolerability in specific patient subpopulations. Aliment Pharmacol Ther 2008; 27(11): 1094-102.
[http://dx.doi.org/10.1111/j.1365-2036.2008.03688.x] [PMID: 18363894]
[22]
Wang Y, Parker CE, Feagan BG, MacDonald JK. Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev 2016; 2016(5)CD000544
[http://dx.doi.org/10.1002/14651858.CD000544.pub4] [PMID: 27158764]
[23]
Feagan BG, Chande N, MacDonald JK. Are there any differences in the efficacy and safety of different formulations of Oral 5-ASA used for induction and maintenance of remission in ulcerative colitis? evidence from cochrane reviews. Inflamm Bowel Dis 2013; 19(9): 2031-40.
[http://dx.doi.org/10.1097/MIB.0b013e3182920108] [PMID: 23811638]
[24]
Meucci G, Fasoli R, Saibeni S, et al. IG-IBD. Prognostic significance of endoscopic remission in patients with active ulcerative colitis treated with oral and topical mesalazine: a prospective, multicenter study. Inflamm Bowel Dis 2012; 18(6): 1006-10.
[http://dx.doi.org/10.1002/ibd.21838] [PMID: 21830282]
[25]
Le Berre C, Roda G, Nedeljkovic Protic M, Danese S, Peyrin-Biroulet L. Modern use of 5-aminosalicylic acid compounds for ulcerative colitis. Expert Opin Biol Ther 2020; 20(4): 363-78.
[http://dx.doi.org/10.1080/14712598.2019.1666101] [PMID: 31498003]
[26]
Ford AC, Khan KJ, Achkar JP, Moayyedi P. Efficacy of oral vs. topical, or combined oral and topical 5-aminosalicylates, in Ulcerative Colitis: systematic review and meta-analysis. Am J Gastroenterol 2012; 107(2): 167-76.
[http://dx.doi.org/10.1038/ajg.2011.410] [PMID: 22108446]
[27]
Römkens TEH, Kampschreur MT, Drenth JPH, van Oijen MG, de Jong DJ. High mucosal healing rates in 5-ASA-treated ulcerative colitis patients: results of a meta-analysis of clinical trials. Inflamm Bowel Dis 2012; 18(11): 2190-8.
[http://dx.doi.org/10.1002/ibd.22939] [PMID: 22419617]
[28]
Rubin DT, Bradette M, Gabalec L, et al. Ulcerative Colitis Remission Study Group. Ulcerative colitis remission status after induction with Mesalazine predicts maintenance outcomes: the MOMENTUM Trial. J Crohn’s Colitis 2016; 10(8): 925-33.
[http://dx.doi.org/10.1093/ecco-jcc/jjw049] [PMID: 26908939]
[29]
Bajpai M, Seril DN, Van Gurp J, et al. Effect of long-term mesalamine therapy on cancer-associated gene expression in colonic mucosa of patients with ulcerative colitis. Dig Dis Sci 2019; 64(3): 740-50.
[http://dx.doi.org/10.1007/s10620-018-5378-8] [PMID: 30478770]
[30]
Lasson A, Öhman L, Stotzer PO, et al. Pharmacological intervention based on fecal calprotectin levels in patients with ulcerative colitis at high risk of a relapse: A prospective, randomized, controlled study. United European Gastroenterol J 2015; 3(1): 72-9.
[http://dx.doi.org/10.1177/2050640614560785] [PMID: 25653861]
[31]
Prieux-Klotz C, Nahon S, Amiot A, et al. Rate and predictors of mucosal healing in ulcerative colitis treated with thiopurines: results of a multicentric cohort study. Dig Dis Sci 2017; 62(2): 473-80.
[http://dx.doi.org/10.1007/s10620-016-4374-0] [PMID: 27853898]
[32]
Giugliano FP, Strisciuglio C, Martinelli M, et al. Does Azathioprine induce endoscopic and histologic healing in pediatric inflammatory bowel disease? A prospective, observational study. Dig Liver Dis 2018; 50(3): 240-6.
[http://dx.doi.org/10.1016/j.dld.2017.10.017] [PMID: 29174208]
[33]
Papamichael K, Cheifetz AS. Use of anti-TNF drug levels to optimise patient management. Frontline Gastroenterol 2016; 7(4): 289-300.
[http://dx.doi.org/10.1136/flgastro-2016-100685] [PMID: 28839870]
[34]
Nasuno M, Miyakawa M, Tanaka H, Motoya S. Short- and Long-Term Outcomes of Infliximab Treatment for Steroid-Refractory Ulcerative Colitis and Related Prognostic Factors: A Single-Center Retrospective Study. Digestion 2017; 95(1): 67-71.
[http://dx.doi.org/10.1159/000452459] [PMID: 28052276]
[35]
Papamichael K, Rakowsky S, Rivera C, Cheifetz AS, Osterman MT. Infliximab trough concentrations during maintenance therapy are associated with endoscopic and histologic healing in ulcerative colitis. Aliment Pharmacol Ther 2018; 47(4): 478-84.
[http://dx.doi.org/10.1111/apt.14458] [PMID: 29210094]
[36]
Little RD, Taylor KM, Friedman AB, et al. A treat-to-target approach via a virtual clinic amongst inflammatory bowel disease patients with secondary loss of response to anti-TNF agents improves clinical outcomes. J Gastroenterol Hepatol 2016; 31: 141.
[37]
Naviglio S, Lacorte D, Lucafò M, et al. Causes of treatment failure in children with Inflammatory Bowel Disease treated with Infliximab: a pharmacokinetic study. J Pediatr Gastroenterol Nutr 2019; 68(1): 37-44.
[http://dx.doi.org/10.1097/MPG.0000000000002112] [PMID: 30211845]
[38]
Magro F, Lopes SI, Lopes J, et al. Portuguese IBD group. [GEDII Histological outcomes and predictive value of faecal markers in moderately to severely active ulcerative colitis patients receiving infliximab. J Crohn’s Colitis 2016; 10(12): 1407-16.
[http://dx.doi.org/10.1093/ecco-jcc/jjw112] [PMID: 27226417]
[39]
Tursi A, Elisei W, Picchio M, et al. Managing ambulatory ulcerative colitis patients with infliximab: a long term follow-up study in primary gastroenterology centers. Eur J Intern Med 2014; 25(8): 757-61.
[http://dx.doi.org/10.1016/j.ejim.2014.07.007] [PMID: 25086677]
[40]
Sugimoto K, Ikeya K, Kato M, et al. Assessment of long-term efficacy and safety of Adalimumab in patients with ulcerative colitis: results from a 6-year real-world clinical practice. Dig Dis 2019; 37(1): 11-20.
[http://dx.doi.org/10.1159/000493121] [PMID: 30205400]
[41]
Fernández-Blanco JI, Fernández-Díaz G, Cara C, Vera MI, Olivares D, Taxonera C. Adalimumab for induction of histological remission in moderately to severely active ulcerative colitis. Dig Dis Sci 2018; 63(3): 731-7.
[http://dx.doi.org/10.1007/s10620-018-4935-5] [PMID: 29372480]
[42]
Juncadella A, Papamichael K, Vaughn BP, Cheifetz AS. Maintenance Adalimumab Concentrations Are Associated with Biochemical, Endoscopic, and Histologic Remission in Inflammatory Bowel Disease. Dig Dis Sci 2018; 63(11): 3067-73.
[http://dx.doi.org/10.1007/s10620-018-5202-5] [PMID: 30006816]
[43]
Sands BE, Peyrin-Biroulet L, Loftus EV Jr, et al. VARSITY Study Group. Vedolizumab versus Adalimumab for moderate-to-severe ulcerative colitis. N Engl J Med 2019; 381(13): 1215-26.
[http://dx.doi.org/10.1056/NEJMoa1905725] [PMID: 31553834]
[44]
Loftus EV Jr, Colombel JF, Feagan BG, et al. Long-term efficacy of vedolizumab for ulcerative colitis. J Crohn’s Colitis 2017; 11(4): 400-11.
[PMID: 27683800]
[45]
Ungaro RC, Yarur A, Jossen J, et al. Higher trough vedolizumab concentrations during maintenance therapy are associated with corticosteroid-free remission in inflammatory bowel disease. J Crohn’s Colitis 2019; 13(8): 963-9.
[http://dx.doi.org/10.1093/ecco-jcc/jjz041] [PMID: 31087100]
[46]
Arijs I, De Hertogh G, Lemmens B, et al. Effect of vedolizumab (anti-α4β7-integrin) therapy on histological healing and mucosal gene expression in patients with UC. Gut 2018; 67(1): 43-52.
[http://dx.doi.org/10.1136/gutjnl-2016-312293] [PMID: 27802155]
[47]
Peyrin-Biroulet L, Panés J, Chiorean M, et al. Histological remission and mucosal healing in a randomised, placebocontrolled,Phase 2 study of etrasimod in patients with moderately to severely active ulcerative colitis. ECCO 2019 OP09 2019 230 October; 10 www.ecco-ibd.eu/publications/congress-abstract-s/abstracts-2019/item/op09-histological-remission-and-mucosal-healing-in-a-randomised-placebo-controlled-phase-2-study-of-etrasimod-in-patients-with-moderately-to-severely-active-ulcerative-colitis.html
[48]
Bryant RV, Costello SP, Schoeman S, et al. Limited uptake of ulcerative colitis “treat-to-target” recommendations in real-world practice. J Gastroenterol Hepatol 2018; 33(3): 599-607.
[http://dx.doi.org/10.1111/jgh.13923] [PMID: 28806471]
[49]
Römkens TE, Gijsbers K, Kievit W, Hoentjen F, Drenth JP. Treatment targets in inflammatory bowel disease: current status in daily practice. J Gastrointestin Liver Dis 2016; 25(4): 465-71.
[http://dx.doi.org/10.15403/jgld.2014.1121.254.ken] [PMID: 27981302]
[50]
Yokomizo L, Limketkai B, Park KT. Cost-effectiveness of adalimumab, infliximab or vedolizumab as first-line biological therapy in moderate-to-severe ulcerative colitis. BMJ Open Gastroenterol 2016; 3(1)e000093
[http://dx.doi.org/10.1136/bmjgast-2016-000093] [PMID: 27195130]
[51]
Ananthakrishnan AN, Korzenik JR, Hur C. Can mucosal healing be a cost-effective endpoint for biologic therapy in Crohn’s disease? A decision analysis. Inflamm Bowel Dis 2013; 19(1): 37-44.
[http://dx.doi.org/10.1002/ibd.22951] [PMID: 22416019]
[52]
Panaccione R, Colombel JF, Bossuyt P, et al. Long-term costeffectiveness of tight control for Crohn’s disease with adalimumabbased treatment: economic evaluation beyond 48 weeks of CALM trial. J Crohns Colitis 2018.12(Supplement 1) 074-075.
[53]
Allocca M, Fiorino G, Bonovas S, et al. Accuracy of Humanitas Ultrasound Criteria in Assessing Disease Activity and Severity in Ulcerative Colitis: A Prospective Study. J Crohn’s Colitis 2018; 12(12): 1385-91.
[http://dx.doi.org/10.1093/ecco-jcc/jjy107] [PMID: 30085066]
[54]
Molander P, Sipponen T, Kemppainen H, et al. Achievement of deep remission during scheduled maintenance therapy with TNFα-blocking agents in IBD. J Crohn’s Colitis 2013; 7(9): 730-5.
[http://dx.doi.org/10.1016/j.crohns.2012.10.018] [PMID: 23182163]
[55]
Itzkowitz SH, Yio X. Inflammation and cancer IVColorectal cancer in inflammatory bowel disease: the role of inflammation Am J Physiol Gastrointest Liver Physiol 2004. 287: G7e17.
[56]
Peyrin-Biroulet L, Lopez A, Cummings JRF, Dignass A, Detlie TE, Danese S. Review article: treating-to-target for inflammatory bowel disease-associated anaemia. Aliment Pharmacol Ther 2018; 48(6): 610-7.
[http://dx.doi.org/10.1111/apt.14922] [PMID: 30069896]
[57]
Mosli MH, Zou G, Garg SK, et al. C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis. Am J Gastroenterol 2015; 110(6): 802-19.
[http://dx.doi.org/10.1038/ajg.2015.120] [PMID: 25964225]
[58]
Narang V, Kaur R, Garg B, et al. Association of endoscopic and histological remission with clinical course in patients of ulcerative colitisIntest Res 2018; 16(1): 55-61.
[http://dx.doi.org/10.5217/ir.2018.16.1.55] [PMID: 29422798]

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