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. 2019 Jun;114(6):874-883.
doi: 10.14309/ajg.0000000000000183.

A Treat-to-Target Update in Ulcerative Colitis: A Systematic Review

Ryan Ungaro  1 , Jean-Frédéric Colombel  1 , Trevor Lissoos  2 , Laurent Peyrin-Biroulet  3
Affiliations

A Treat-to-Target Update in Ulcerative Colitis: A Systematic Review

Ryan Ungaro et al. Am J Gastroenterol. 2019 Jun.

Abstract

Objectives: In 2015, the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program proposed shifting the therapeutic focus on ulcerative colitis (UC) toward altering the natural history of the disease course by regularly monitoring objective measurements of disease activity and tailoring treatment accordingly. The therapeutic paradigm shift was well received in the research community and is often cited. However, new evidence on optimal UC treatment targets continues to accumulate since the time of the STRIDE guidelines. This systematic review summarizes the evidence accrued since the STRIDE UC recommendations, discusses the barriers for adoption of treat-to-target approaches in clinical practice in UC, and suggests directions for future research.

Methods: We systematically reviewed MEDLINE for studies from the time of the STRIDE systematic review up to March 31, 2018, that assessed the potential treatment targets identified by the STRIDE recommendations.

Results: Each potential treatment target literature search returned > 200 articles, which were then reviewed by 2 independent investigators for relevant studies. Selected studies of clinical factors, patient-reported outcomes, endoscopy, histology, imaging, and biomarkers and implications on treatment targets are summarized.

Conclusions: It appears that the relative weight given to different therapeutic targets in the development and improvement of UC treatments could be optimized, with an increased emphasis on endoscopic and histological targets over clinical or symptomatic targets. For this evolution to occur, however, new research has to demonstrate that the treat-to-target approach will deliver on the promise of better long-term outcomes compared with current approaches.

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Figures

Figure 1.
Figure 1.
Accumulating evidence and evolution of specific targets in the management of UC. CRP, C-reactive protein; PRO, patient-reported outcomes; UCEIS, UC Endoscopic Index of Severity.
Figure 2.
Figure 2.
Feasibility of and barriers to implementation of a T2T approach. In the above matrices, the targets are placed on a scale that accounts for the ease of implementation as a treatment target (x-axis) and perceived impact of treatment target on disease outcome (y-axis). Quadrant 1 contains targets that are difficult to implement but have high perceived impact by stakeholder, quadrant 2 contains targets that are easy to implement and have high perceived impact, quadrant 3 contains targets that are difficult to implement and have low perceived impact, and finally quadrant 4 contains targets that are easy to implement and have low perceived impact. Each stakeholder will require different levels of evidence and education to successfully adopt the treat-to-target approach proposed by the STRIDE committee. Barriers to implementation are summarized under each matrix. PRO, patient-reported outcomes; QoL, quality of life; T2T, treat-to-target; STRIDE, Selecting Therapeutic Targets in Inflammatory Bowel Disease.
Figure 3.
Figure 3.
Proposed ulcerative colitis T2T algorithm. aMucosal healing as a treatment target must involve patient decision because of the high burden of monitoring and potential need for therapy escalation despite symptom resolution. bBiomarker normalization as a treatment target must involve patient decision because of potential need for therapy escalation despite symptom resolution. cIf adjunctive biomarkers are not improving or normalizing, mucosal healing targets should be reassessed. QoL, quality of life; RHI, Robarts Histopathology Index; T2T, treat-to-target; UCEIS, UC Endoscopic Index of Severity.
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