Treat to Target in Inflammatory Bowel Disease
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With the expanding armamentarium in IBD the current treatment targets can be reached. By optimally using our drugs we can avoid long-term complications in IBD. For this the therapeutic strategy has to be changed from a clinically driven approach to a target-driven strategy. Currently mucosal healing, normalization of biomarkers, histological healing, and healing on abdominal imaging are proposed targets. Correct phenotyping of the patient before initiation of therapy is mandatory. Once treatment is initiated a continuous re-evaluation with consequent adaptation of the treatment when goals are not (yet) reached is needed. Both escalation and de-escalation should be considered. Drug levels can be used as a guidance to reach these targets.
KeywordsTreat to target Mucosal healing Biomarkers MRE Histological healing IBD
Compliance with Ethical Standards
Conflict of Interest
Peter Bossuyt reports grants from Abbvie, consultancy or speakers fees from Mundipharma, MSD, Robarts, and Hospira, outside the submitted work.
Séverine Vermeire reports grants from Abbvie, Takeda, MSD, and consultancy or speakers fees paid to the institution from Abbvie, Takeda, MSD, Pfizer, Genentech/Roche, Galapagos, Hospira, Mundipharma, J&J, Shire, Ferring, and Cellgene.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading
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- 1.Hindryckx P, Baert F, Hart A, Magro F, Armuzzi A, Peyrin-Biroulet L, et al. Clinical trials in ulcerative colitis: a historical perspective. J Crohns Colitis. 2015.Google Scholar
- 6.Stoffer MA, Schoels MM, Smolen JS, Aletaha D, Breedveld FC, Burmester G, et al. Evidence for treating rheumatoid arthritis to target: results of a systematic literature search update. Ann Rheum Dis. 2015.Google Scholar
- 7.••Smolen JS, Breedveld FC, Burmester GR, Bykerk V, Dougados M, Emery P, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis. 2015. This article reviews the current evidence for a workable treat-to-target strategy in rheumatoid arthritis. These recommendations are the framework for further clinical trial of a treat to target strategy in IBD.Google Scholar
- 10.Pope JE, Haraoui B, Rampakakis E, Psaradellis E, Thorne C, Sampalis JS, et al. Treating to a target in established active rheumatoid arthritis patients receiving a tumor necrosis factor inhibitor: results from a real-world cluster-randomized adalimumab trial. Arthritis Care Res. 2013;65(9):1401–9.CrossRefGoogle Scholar
- 11.Schipper LG, Vermeer M, Kuper HH, Hoekstra MO, Haagsma CJ, Den Broeder AA, et al. A tight control treatment strategy aiming for remission in early rheumatoid arthritis is more effective than usual care treatment in daily clinical practice: a study of two cohorts in the Dutch rheumatoid arthritis monitoring registry. Ann Rheum Dis. 2012;71(6):845–50.CrossRefPubMedGoogle Scholar
- 12.Soubrier M, Lukas C, Sibilia J, Fautrel B, Roux F, Gossec L, et al. Disease activity score-driven therapy versus routine care in patients with recent-onset active rheumatoid arthritis: data from the GUEPARD trial and ESPOIR cohort. Ann Rheum Dis. 2011;70(4):611–5.CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Peyrin-Biroulet L, Sandborn W, Sands BE, Reinisch W, Bemelman W, Bryant RV, et al. Selecting therapeutic targets in inflammatory bowel disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol. 2015.Google Scholar
- 29.Theede K, Holck S, Ibsen P, Ladelund S, Nordgaard-Lassen I, Nielsen AM. Level of fecal calprotectin correlates with endoscopic and histologic inflammation and identifies patients with mucosal healing in ulcerative colitis. Clin Gastroenterol Hepatol. 2015.Google Scholar
- 30.Sandborn WJ, Panes J, Zhang H, Yu D, Niezychowski W, Su C. Correlation between concentrations of fecal calprotectin and outcomes of patients with ulcerative colitis in a phase 2 trial. Gastroenterology. 2015.Google Scholar
- 32.Guidi L, Marzo M, Andrisani G, Felice C, Pugliese D, Mocci G, et al. Faecal calprotectin assay after induction with anti-tumour necrosis factor alpha agents in inflammatory bowel disease: prediction of clinical response and mucosal healing at one year. Dig Liver Dis. 2014;46(11):974–9.CrossRefPubMedGoogle Scholar
- 34.Guardiola J, Lobaton T, Rodriguez-Alonso L, Ruiz-Cerulla A, Arajol C, Loayza C, et al. Fecal level of calprotectin identifies histologic inflammation in patients with ulcerative colitis in clinical and endoscopic remission. Clin Gastroenterol Hepatol. 2014;12(11):1865–70.CrossRefPubMedGoogle Scholar
- 44.Sulz MC, Siebert U, Arvandi M, Gothe RM, Wurm J, von Kanel R, et al. Predictors for hospitalization and outpatient visits in patients with inflammatory bowel disease: results from the Swiss inflammatory bowel disease cohort study. Eur J Gastroenterol Hepatol. 2013;25(7):790–7.CrossRefPubMedGoogle Scholar
- 45.Koutroubakis IE, Regueiro M, Schoen RE, Ramos-Rivers C, Hashash JG, Schwartz M, et al. Multiyear patterns of serum inflammatory biomarkers and risk of colorectal neoplasia in patients with ulcerative colitis. Inflamm Bowel Dis. 2015.Google Scholar
- 47.Kiss LS, Papp M, Lovasz BD, Vegh Z, Golovics PA, Janka E, et al. High-sensitivity C-reactive protein for identification of disease phenotype, active disease, and clinical relapses in Crohn’s disease: a marker for patient classification? Inflamm Bowel Dis. 2012;18(9):1647–54.CrossRefPubMedGoogle Scholar
- 49.Kiss LS, Szamosi T, Molnar T, Miheller P, Lakatos L, Vincze A, et al. Early clinical remission and normalisation of CRP are the strongest predictors of efficacy, mucosal healing and dose escalation during the first year of adalimumab therapy in Crohn’s disease. Aliment Pharmacol Ther. 2011;34(8):911–22.CrossRefPubMedGoogle Scholar
- 55.Cornillie F, Hanauer SB, Diamond RH, Wang J, Tang KL, Xu Z, et al. Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: a retrospective analysis of the ACCENT I trial. Gut. 2014;63(11):1721–7.CrossRefPubMedPubMedCentralGoogle Scholar
- 58.••Vande Casteele N, Ferrante M, Van Assche G, Ballet V, Compernolle G, Van Steen K, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology. 2015;148(7):1320–9.e3. This paper highlights the value of anti-TNF dose optimization in IBD. Optimal anti-TNF drug levels in maintenance therapy favors achieving treatment targets.CrossRefPubMedGoogle Scholar
- 61.•Ordas I, Rimola J, Rodriguez S, Paredes JM, Martinez-Perez MJ, Blanc E, et al. Accuracy of magnetic resonance enterography in assessing response to therapy and mucosal healing in patients with Crohn’s disease. Gastroenterology. 2014;146(2):374–82.e1. This article demonstrates the good correlation between MRE and endoscopy. It also highlights the role of MRE scores in the evaluation of treatment response.CrossRefPubMedGoogle Scholar
- 65.Sauer CG, Middleton JP, McCracken C, Loewen J, Braithwaite K, Alazraki A, et al. Magnetic resonance enterography (MRE) healing and MRE remission predicts improved outcome in pediatric Crohn disease. J Pediatr Gastroenterol Nutr. 2015.Google Scholar
- 76.•Bouguen G, Levesque BG, Pola S, Evans E, Sandborn WJ. Feasibility of endoscopic assessment and treating to target to achieve mucosal healing in ulcerative colitis. Inflamm Bowel Dis. 2014;20(2):231–9. This article—although retrospective—highlights the importance of early re-evaluation after initiation of a treatment in IBD.CrossRefPubMedGoogle Scholar
- 77.•Bouguen G, Levesque BG, Pola S, Evans E, Sandborn WJ. Endoscopic assessment and treating to target increase the likelihood of mucosal healing in patients with Crohn’s disease. Clin Gastroenterol Hepatol. 2014;12(6):978–85. This article—although retrospective—highlights the importance of early re-evaluation after initiation of a treatment in IBD.CrossRefPubMedGoogle Scholar