Joseph Feuerstein, MD, on the AGA Clinical Guidelines for Managing Moderate to Severe Ulcerative Colitis

Earlier this year, the American Gastroenterological Association (AGA) issued updated clinical guidelines for the management of moderate to severe ulcerative colitis (UC) in outpatients as well as in hospitalized patients with acute severe UC (ASUC). Joseph Feuerstein, MD, served as chair of the Clinical Guidelines Committee. Dr Feuerstein, from Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, answered some questions for Gastroenterology Learning Network about the project.

GASTROENTEROLOGY LEARNING NETWORK: What initiated this update to the clinical guidelines for managing moderate to severe UC: new data, new therapeutic agents, new thinking about how best to approach treatment?

Dr Feuerstein: The field of inflammatory bowel disease and specifically ulcerative colitis is an ever-evolving field. There are increasing numberS of new drugs and classes of drugs that have been approved. Additionally, our approach to care has changed dramatically. In clinical practice we no longer manage patients with a step-therapy approach but rather we try to address the disease based on the disease severity with the best drug available to use for that disease severity.

GLN: There was only one strong recommendation in the guidelines—that infliximab, adalimumab, golimumab, vedolizumab, tofacitinib, or ustekinumab are recommended over no treatment for moderate to severe UC. What evidence do you look for when deciding to make strong vs conditional recommendations? What is needed in terms of data, length of time a drug is on the market, etc?

Dr Feuerstein: The challenge with a strong recommendation in the GRADE system is that we really remove the subjective nature of the recommendations. The recommendation is based on specific criteria defined in GRADE methodology. There is the underlying evidence and overall quality of evidence available. In most cases, this is the major rate-limiting step for the ability to make a strong recommendation. The strength of the recommendation is rooted in the evidence, risks of harms, benefits, costs, patient values and preferences, and more. The idea is that you do not just choose to rate something as a strong recommendation if you think it is a good idea. It is a very standardized way of looking at the evidence. The lack of many strong recommendation is more based on the fact that we really do need higher quality trials and data to inform clinicians.

GLN:  The guidelines state that the critical outcomes for decision-making for adults with moderate to severe UC were induction and maintenance of remission, and for hospitalized adults with acute severe UC (ASUC) the critical outcome was the risk of colectomy risk within 3 months of hospitalization. Have you seen improvements in these outcomes over the past few years, as new therapies have been approved for UC?

Dr Feuerstein: Anecdotally, I do think that we have seen an improvement. Recently, some studies have suggested this improvement, as well. Conceptually it makes sense that if someone is healed up that they would do better, but we really do need concrete evidence to definitively tell us that we have reduced both the short-term risks and long-term risks of drug failure and colectomy.

GLN: In the 2017 Global Burden of Disease Study, researchers found that the prevalence of inflammatory bowel diseases (IBD), including UC, had increased substantially since 1990 in higher-income nations, and also rose rapidly in newly industrialized countries. How might the new guidelines help physicians prepare to treat more patients with UC in the future?

Dr Feuerstein: The new guideline tries to take a more 20^th-century approach to managing these patients. The guideline has separated out mild to moderate UC, which was addressed earlier by the AGA, and now moderate to severe UC. It focuses that patients should be treated based on severity of disease and efficacy of drug therapy. One key part to the guideline is that we cannot continue with step-therapy recommendations that require failure of older, ineffective agents for moderate to severe UC.

GLN: Did you discover anything that surprised you as you reviewed the data, study results, and other information that went into developing the guidelines—either positive or negative?

Dr Feuerstein: I think it was less of a surprise at the findings and more of a vindication that most of what we practice nowadays is really supported by the evidence and now we have this document that provides the background information we need to support our current practice.

GLN: In this update the authors noted that the next update to the guidelines is anticipated in 3 years. Given the pace of change in therapeutics, do you foresee the need for these updates to be done more often in the future? How do you suggest that clinicians stay up to date on the best treatment strategies between guideline updates?

Dr Feuerstein: I do think we will need more frequent updates. I think there are many tools and mechanisms for clinicians to stay more up to date. There are many email summaries that we get on a daily basis summarizing the evidence. There are lots of GI conferences now throughout the year and there are many IBD conferences held all over that provide key updates on a regular basis.

GLN: What does the future hold for patients with UC in terms of advances in treatment?

Dr Feuerstein: I think the future for UC is going to focus on much more gut-selective targeted therapies with lower risks of side effects and lower risks of complications. I think we will eventually be able to test patient’s immune system to determine which pathway is activated and then utilize a more appropriate drug that is specifically designed to target/block that pathway.

Reference: 

Feuerstein JD, Isaacs KL, Schneider Y, et al, on behalf of the AGA Institute Clinical Guidelines Committee. AGA clinical practice guidelines on the management of moderate to severe ulcerative colitis. Gastroenterology. 2020;158(5):1450-1461. doi.org/10.1053/j.gastro.2020.01.006