June 7, 2022

Adopting a Precision Medicine Approach to Outcome Prediction in Inflammatory Bowel Disease

Renewed funding accelerates Rieder lab discoveries


Inflammatory bowel disease (IBD) was once generally considered a dichotomous disease group. Patients either suffered from Crohn’s disease (CD) or ulcerative colitis (UC) and were treated accordingly.


Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

Genetic discoveries have challenged this traditional view, with an emerging understanding of IBD as a heterogenous condition with a range of subphenotypes with varying levels of severity and responses to treatment types. And yet, much of clinical medicine continues to reflect the traditional view of IBD.

“Right now, we have a standardized approach to our patients because we lack the biomarkers to differentiate their needs,” says Florian Rieder, MD, Vice Chair of the Department of Gastroenterology, Hepatology and Nutrition and Director of Inflammatory Bowel Diseases Research at Cleveland Clinic. “To reflect the reality of the diseases we treat, we must move more rapidly and systematically toward a precision medicine approach.”

A precision approach for an individualized disease

Not only is IBD genetically heterogenous, but current treatments also differ in efficacy and side effect profiles among individual patients. Anti-tumor necrosis factor (TNF) treatment is a primary pharmacological approach, but almost 40% of patients experience primary nonresponse, while 40% of initial responders experience nonresponse within a year.

“With many patients, the more we use these medications, the less effective they become,” says Dr. Rieder. “It’s also very common for patients to discontinue the medication due to severe side effects. If we could identify biomarkers that reliably predict which patients will have a disease course that necessitates pharmacological intervention and then which patients will respond to a particular medication, we can save a lot of morbidity and mortality.”

Moving beyond short-term thinking

One of the primary challenges to shifting to a precision medicine approach for IBD treatment is that current studies mostly focus on short-term treatment response as an endpoint. “We do have some precision tools we use in predicting responses to or complications from particular therapies in the short term, such as blood, genetic and fecal biomarkers,” says Dr. Rieder.


Short-term treatment response is a meaningful endpoint, but research has shown that it does not correlate with rates of future tissue damage and remodeling. “Since more than half of patients with CD experience stricturing disease, we must shift our focus from short-term treatment response to predictive biomarkers that recognize the separate mechanisms driving inflammation and tissue damage,” he says.

Validated predictive biomarkers to define future disease course are lacking in essentially all major areas of IBD, Dr. Rieder and three other leading researchers note in a recent issue of Gastroenterology. “Future precision approaches should aim to proactively escalate immune suppression on the basis of preclinical biomarkers to prevent an otherwise aggressive future disease course,” they write. “Approaches should identify features that would favor one immune-targeted regimen over another in a specific individual.”

Another challenge is to embrace the complexity of systems biology in studies geared toward prediction. Current studies consider gene and environment interactions separately, but Dr. Rieder advocates a multimodal omics approach that attempts to capture the totality of the genome, microbiome or exposome.

“Traditional prediction studies don’t account for our advancing understanding of IBD pathogenesis, which necessitates a systems biology approach that allows us to integrate analyses of individual ‘-omes’ into a whole result that is greater than the sum of its parts,” he says. “Ideally, we can measure thousands of biomarkers in an unbiased approach and allow artificial intelligence to analyze these from multiple tissues of multiple patients over time.”

Grant renewal advances precision medicine for stricturing CD

The Leona M. and Harry B. Helmsley Charitable Trust recently awarded a $5.3 million grant renewal to Cleveland Clinic, Mayo Clinic and Alimentiv, Inc., to expand support for the Stenosis Therapy and Anti-Fibrotic Research (STAR) consortium.


With its initial grant, the consortium developed and validated outcome measures that would enable the first patient trials of anti-fibrotic therapies. With the grant renewal, STAR hopes to refine the clinical trial population through a derivation and validation approach. Dr. Rieder’s lab in Cleveland Clinic’s Lerner Research Institute is focused on the molecular analysis aspect of the project.

“Right now, we don’t have any selective anti-fibrotic therapy or biomarkers,” says Dr. Rieder, co-leader of the consortium, for which Cleveland Clinic is the coordinating center. “That patient population has been poorly defined, and even the definition of a stricture isn’t standard across studies. Our initial hope is to create a global consensus defining the stricture patient, with links to pathology as the gold standard.”

The end goal? A validated mucosal biomarker that can inform treatment decisions and define clinical trial populations. “The bottom line in precision medicine is the right approach at the right moment for each individual patient,” he says. “That’s what we hope to achieve.”

Related Articles

Impostor phenomenon
February 6, 2024
Recognizing the Impact of Impostor Phenomenon and Microaggressions in Gastroenterology

The importance of raising awareness and taking steps to mitigate these occurrences

Koji Hashimoto, MD, and team
February 2, 2024
Combined Cardiac Surgery and Liver Transplant Is a New Option for Highly Selected Patients

New research indicates feasibility and helps identify which patients could benefit

December 8, 2023
MILU Improves Outcomes Among Critically Ill Patients with Advanced Liver Disease

Standardized and collaborative care improves liver transplantations

November 17, 2023
Younger Patients with Alcohol-Associated Hepatitis Present to the ED More Often, Research Shows

Caregiver collaboration and patient education remain critical

food allergies
October 26, 2023
What Gastroenterologists Need to Know About Managing Food Allergies in Clinical Practice

Beyond recognizing and treating food allergies, GIs also have a responsibility to address common food allergy misconceptions

October 25, 2023
ChatGPT “Pretty Good” at Basic IBS Info, but Misses Details

Important to recognize limitations when it comes to healthcare and research

celiac disease
October 24, 2023
Women’s Health Disorders Found More Frequently Among Individuals With Celiac Disease

Findings reinforce the importance of multidisciplinary care

Miguel Reguiero, MD
October 23, 2023
No Link Between Small Molecule Therapies and Cardiovascular Events in New IBD Study

Underlying inflammation may cause higher rates of CV events