Treatment endpoints in ulcerative colitis: Does one size fit all?

Abstract

A treat-to-target strategy in inflammatory bowel disease (IBD) involves treatment intensification in order to achieve a pre-determined endpoint. Such uniform and tight disease control has been demonstrated to improve clinical outcomes compared to treatment driven by a clinician’s subjective assessment of symptoms. However, choice of treatment endpoints remains a challenge in management of IBD via a treat-to-target strategy. The treatment endpoints for ulcerative colitis (UC), recommended by the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) consensus have changed somewhat over time. The latest STRIDE-II consensus advises immediate (clinical response), intermediate (clinical remission and biochemical normalisation) and long-term treatment (endoscopic healing, absence of disability and normalisation of health-related quality of life, as well as normal growth in children) endpoints in UC. However, achieving deeper levels of remission, such as histologic normalisation or healing of the gut barrier function, may further improve outcomes among UC patients. Generally, all medical therapy should seek to improve short- and long-term mortality and morbidity. Hence treatment endpoints should be chosen based on their ability to predict for improvement in short- and long-term mortality and morbidity. Potential benefits of treatment intensification need to be weighed against the potential harms within an individual patient. In addition, changing therapy that has achieved partial response may lead to worse outcomes, with failure to recapture response on treatment reversion. Patients may also place different emphasis on certain potential benefits and harms of various treatments than clinicians, or may have strong opinions re certain therapies. Potential benefits and harms of therapies, incremental benefits of achieving deeper levels of remission, as well as uncertainties of the same, need to be discussed with individual patients, and a treatment endpoint agreed upon with the clinician. Future research should focus on quantifying the incremental benefits and risks of achieving deeper levels of remission, such that clinicians and patients can make an informed decision about appropriate treatment end-point on an individual basis.

Keywords: Ulcerative colitis; Treatment endpoints; Endoscopic remission; Histologic remission; Biomarkers; Gut barrier healing

Core Tip: Recently, more stringent treatment endpoints have emerged such as histologic remission and functional gut barrier healing, which may be better predictors of clinically important outcomes compared to mucosal healing. However, pursuing deeper levels of remission in ulcerative colitis patients can have risks. Treatment endpoints in ulcerative colitis should be set with two thresholds, minimum and ideal endpoints to be achieved. Endpoints also need to be appropriate for both the follow up timeframe and the treatment selected. Individual patient circumstances need to be taken into account in selecting endpoints, as at times relaxed treatment endpoints are appropriate.