What did STRIDE recommend about treat to target in IBD?

By Mark S. Silverberg, MD Volume 2 - Issue 5

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Treat to target in IBD

The goal of a treat-to-target strategy for inflammatory bowel disease (IBD) can be directly transferred from the approach developed for rheumatoid arthritis (RA), by substituting IBD for RA as the disease of interest, and articulated as follows:(1)

“The primary goal of treating patients with IBD is to maximize long-term health-related quality of life through control of symptoms, prevention of structural damage, normalization of function and participation in social and work-related activities.”(1)

This goal requires measurement of both clinical and endoscopic targets.(1) Patient-reported outcomes (PROs) measure the patient’s experience of the disease and impact of treatment. Normalization of quality of life with treatment in comparison with that before disease onset is the definitive PRO.(2) Symptoms affecting quality of life must be addressed and treatment goals tailored to the individual circumstances of each patient. Objective measures, such as endoscopic findings, measure the biological expression of the disease.(1) Comprehensive disease and risk factor assessment at diagnosis and at regular intervals in the disease course allows risk stratification and implementation of a treat-to-target strategy, after detailed patient consultation.

Ulcerative colitis

Mucosal healing is a logical treatment target in ulcerative colitis (UC), as hospitalized patients with severe endoscopic lesions have an odds ratio for colectomy of 41 compared with patients without severe lesions.(3) A retrospective cohort study of 60 patients with mild to severe endoscopic UC activity at baseline (mean disease duration 5 years, range 0.7–10.5 years) was performed to determine the feasibility of mucosal healing as a treatment target in UC.(4) Serial endoscopy and adjustment of therapy with findings of continuing disease activity resulted in mucosal healing in 26% at 26 weeks, 52% at 52 weeks and 70% at 76 weeks, demonstrating that mucosal healing is a feasible treatment target in UC.

Crohn’s disease

Despite an extensive literature on predictive factors in Crohn’s disease (CD), risk stratification is complicated by the lack of validated clinical prediction rules or a predictive model as well as the significant heterogeneity found in the CD phenotype.(5) Data from numerous trials indicate mucosal healing is a potential treatment target(5), and the presence of deep or large endoscopic ulcers in patients with CD has been found to increase the risk of colectomy to 31% at 12 months compared with 6% in patients without severe lesions.(3) A retrospective cohort study of 67 CD patients with endoscopic lesions at baseline (median disease duration 9.8 years, range 1.2–21.12 years) was performed to assess the feasibility of using mucosal healing as a treatment target in CD.(6) Serial endoscopy and adjustment of therapy with findings of continuing disease activity resulted in mucosal healing in 12.7% at 24 weeks and 45.0% at 52 weeks.

Patient-reported outcomes (PROs)

With regulatory support, PROs have the potential to become a therapeutic target in IBD.(2) A variety of PROs have been used in clinical trials in IBD, but outcome data are limited. As a result, IBD-specific tools to measure PROs in adults have yet to be developed.

A PRO tool, the TUMMY-UC, is being developed for use in pediatric patients with UC.(7) A multicentre, cross-sectional study consisting of 79 concept elicitation interviews has identified and ranked important symptoms, and additional work will finalize the wording of the tool. A recent study to assess the criterion validity and responsiveness of the Patient-Reported Outcomes Measurement Information System (PROMIS) involved a web-based cohort of 276 children with CD.(8) The study found that PROMIS scores showed a significant linear association with CD activity, health-related quality of life, and responsiveness to disease activity over a 6-month period.

STRIDE recommendations

The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program, initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) examined potential treatment targets in IBD and the evidence supporting them.(2) Based on the evidence and expert opinion, the group developed consensus recommendations for treatment targets for UC and CD. The composite treatment targets for patients with IBD are based on clinical symptoms and PROs plus endoscopic remission. Randomized clinical trial data indicate that intensive therapy should achieve these composite targets in one-third to two-thirds of patients with IBD, based on individual factors, such as disease duration and prior therapy.

Ulcerative colitis

The program agreed that the target for UC was the following:(2)

  • Clinical and patient-reported remission, defined as resolution of rectal bleeding and diarrhea or altered bowel habit (assessed at least every 3 months until resolution, then every 6 to 12 months), plus
  • Endoscopic remission, defined as a Mayo endoscopic subscore of 0 or 1 (assessed 3 to 6 months after starting therapy in symptomatic patients and then at least every 3 months during active disease).

STRIDE considered histologic remission to be an adjunctive target, as insufficient evidence exists to recommend histologic remission as a target in clinical practice.

In UC, the most commonly used endoscopy scoring system is the Mayo Clinic endoscopy subscore.(3) The ulcerative colitis endoscopic index of severity (UCEIS), a new score assessing vascular pattern, bleeding, and erosions and ulcers, is being used in clinical trials, and once validated, may be integrated into clinical practice.

Crohn’s disease

The agreed target for CD was the following: (2)

  • Clinical and patient-reported remission, defined as resolution of abdominal pain and diarrhea or altered bowel habit (assessed at least every 3 months until resolution, then every 6 to 12 months), plus
  • Endoscopic remission, defined as resolution of ulceration at ileocolonoscopy, or resolution of inflammation on cross-sectional imaging, in patients who could not be assessed adequately by ileocolonoscopy (assessed at least every 6 to 9 months during active disease).

STRIDE considered biomarker remission, that is, normalization of C-reactive protein and fecal calprotectin to be an adjunctive target, as insufficient evidence exists to recommend treatment optimization based on biomarkers alone.      

Validated endoscopic scoring systems for CD with good inter-observer agreement are the Crohn’s disease endoscopic index of severity (CDEIS) and the simple endoscopic score for Crohn’s disease (SES-CD).(3) The complexity of the CDEIS generally restricts its use to clinical trials. The SES-CD, which correlates well with the CDEIS, is reliable and measures ulcer size, ulcerated and affected surfaces, and stenosis in 5 bowel segments. Although use of the SES-CD in clinical practice is not widespread, the IOIBD recommends its use in defining endoscopic response and remission.

Elevated fecal calprotectin

In CD, fecal calprotectin may facilitate patient monitoring and act as an adjunctive biomarker of response to therapy and relapse prediction, especially in Crohn’s colitis and after ileocecectomy.(2) Nevertheless, based on the current evidence, fecal calprotectin remains an adjunctive outcome measure that can facilitate monitoring rather than a treatment target. Elevated fecal calprotectin should prompt endoscopic assessment, whether or not the patient is symptomatic.


The treat-to-target approach to therapy has the potential to change patient outcomes. Prospective studies are, however, still needed to determine how effectively this approach changes disease course and patients’ quality of life.(2) Routine endoscopic assessment of disease activity and mucosal healing, despite its limitations, is increasingly becoming the standard of care as part of a treat-to-target strategy in clinical practice.(3)


  1. Bossuyt P, Vermeire S. Treat to target in inflammatory bowel disease. Curr Treat Options Gastro. 2016;14:61–72.
  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;110:1324–38.
  3. Christensen B, Rubin DT. Understanding endoscopic disease activity in IBD: how to incorporate it into practice. Curr Gastroenterol Rep. 2016;18(1):5
  4. Bouguen G, Levesque BG, Pola S, et al. Feasibility of endoscopic assessment and treating to target to achieve mucosal healing in ulcerative colitis. Inflamm Bowel Dis. 2014;20:231–9.
  5. Bouguen G, Levesque BG, Feagan BG, et al. Treat to target: a proposed new paradigm for the management of Crohn’s disease. Clin Gastroenterol Hepatol. 2015;13(6):1042–50.
  6. Bouguen G, Levesque BG, Pola S, et al. Endoscopic assessment and treating to target increase the likelihood of mucosal healing in patients with Crohn’s disease. Clin Gastroenterol Hepatol. 2014;12:978–85.
  7. Marcovitch L, Nissan A, Mack D, et al. Item generation and reduction towards developing a patient reported outcome for pediatric ulcerative colitis (TUMMY-UC). J Pediatr Gastroenterol Nutr. 2016 May 6. [Epub ahead of print]
  8. Arvanitis M, DeWalt DA, Martin CF, et al. Patient-reported outcomes measurement information system in children with Crohn’s disease. J Pediatr. 2016; May 2. [Epub ahead of print]

Special Edition IBD Dialogue 2016 Volume 02: Treat-to-Target in IBD is made possible by an unrestricted educational grant from…