Personalizing IBD Patient Care: From Risk Stratification to Individualized Therapy

Blog | August 04, 2021

Corey A. Siegel, MD, MS
Scientific Advisory Board Member
Trellus Health


Treating inflammatory bowel disease (IBD) used to be easy. It wasn’t remarkably effective, but it was easy. I am a specialist treating Crohn’s disease and ulcerative colitis (UC) and I finished my training in the early 2000s when we had a limited arsenal of drug treatments to choose from:

  • One biologic drug (infliximab)
  • Thiopurines (6-mercaptopurine and azathioprine)
  • Methotrexate
  • Mesalamine
  • Corticosteroids (prednisone)

At that time, after making a diagnosis of IBD and differentiating Crohn’s from UC, we set our patients on a fairly linear pathway. We typically started them with mesalamine, with or without corticosteroids, moved on to thiopurines if those failed, and then infliximab if our patients didn’t get better, and then finally on to surgery — our last resort.

The bottom-up approach was the only approach

This is the famous pyramid or “bottom-up” approach that was used for decades and, in some clinics, it is still being followed. It essentially started patients in the shallow end of the pool, only moving them to the deeper end if, and only if, their disease demanded stronger therapy. It was a straight line with little opportunity for deviation. I

If we tried to skip a step, either the insurance company blocked us, or our patients and colleagues questioned how we could justify using such expensive medications — which included side effects of tuberculosis and an increased risk of cancer and death — before it was the patients only option left. As I said, the treatment progress was easy, but ineffective and did little to change the natural course of a patient’s disease.

Evolving past one-size-fits-all

Over the past 20 years, we have made considerable progress.

First, we have several new treatment options, many more on the way, and a scientific research pipeline that continues to push for more and better therapies.

Second, and perhaps most importantly, is the recognition that patients with IBD experience a broad variation of disease behaviors. Some patients rapidly progressing to irreversible damage and the need for surgery while others have a much more indolent course and may go for many years (or forever) with only mild occasional symptoms.

We now understand that some patients do just fine with the bottom-up pyramidal approach while others need our absolute best medications or combinations of medications right at the time of diagnosis. Else, they are at risk for serious complications from their disease and may need frequent surgeries. The big challenge is to figure out who is who.

Risk stratification tools can guide individualized IBD care

Risk stratification tools have been developed to help us determine which patients are likely to go down a specific disease progression pathway. This allows us to begin individualizing our treatment approach as opposed to treating everyone based on textbook algorithms.

IBD CareNavigator

The American Gastroenterological Association (AGA) has developed a clinical decision tool that uses simple clinical variables (e.g., age, disease extent, deep ulcers on endoscopy, presence of complications) to distinguish patients at low-risk versus moderate- or high-risk of disease progression.

This tool is available online and will recommend a specific treatment class or combination of medications based on this stratification.

CDPATH

Another tool that has become recently available is called CDPATH. CDPATH uses a combination of clinical, serologic (anti-microbial antibodies), and genetic markers to show patients and providers a graph of their predicted time to progression of Crohn’s disease. About 20% of patients fall into the low-risk category with the remaining 80% at medium- to high-risk of progressing to complications (strictures or penetrating disease) within the next three years.

You can imagine how showing this prediction graphic to a patient could strongly guide them to a more or less intensive treatment approach, with the threshold of when to start therapy in the eye of the beholder (the patient) as individuals can then make their own decisions balancing the risk of their disease against the benefits and risks of specific therapies.

CDPATH is now available free of charge for eligible patients with Crohn’s disease — specifics can be found at CDPATH.com.

The next steps

There is still a lot of work to be done in this field, but we are well on our way to helping patients and providers come to a mutual understanding of their prognosis to help guide shared decision-making.

The next step is where the greatest growth in knowledge will come over the next 5–10 years. If patients are of low risk of progression, it’s fairly straightforward as almost any of our currently available medications are probably a reasonable choice. The challenge for the medium-high risk patients is not if to start a highly effective IBD drug, but which one.

Currently, we are admittedly still in a trial-and-error phase. We chose the medication that is at the center of the Venn diagram for patient preference, provider recommendation, and paid for by insurers. We just don’t have a lot more to go on. There are decision support tools available based on clinical trials and real-world data, but there is a long way to go.

The holy grail is diagnosing a patient and then simultaneously performing risk stratification with a tool to predict which medication(s) a patient is most likely to respond to. This is where we need to be.

For now, we must capitalize on what we have available and optimize, optimize, optimize every piece we can control. This is why IBD care is now hard. It is more effective, but it requires focus and diligence. Every patient at the time of diagnosis should have a discussion directed on their individual prognosis, and then we should use all the tools we have available to guide treatment.

We are now able to determine the appropriate dosing for thiopurine drugs, we can now predict which patients are at higher risk of developing antibodies to anti-tumor necrosis factor (TNF) medications, and we are getting even more precise about target goals of drug concentrations for each individual drug.

This is personalized medicine. We are not selecting a drug and putting everyone on the same care plan but modifying the frequency and/or dose for what that patient needs.

  • For patients at higher risk of medication side effects, we have safer drugs
  • For patients at higher risk of rapid progression and need for hospitalization, we have faster-acting drugs

It’s all a balancing act of what is right for an individual patient, and although we have a significant amount to still learn, we have made significant progress in the past 20 years.

Looking ahead

It is never a good time to have Crohn’s disease or ulcerative colitis, but now and looking to the future, it is an exciting time for patients and providers. We will continue to make progress and we will continue to learn and adapt our treatment algorithms accordingly.

I look forward to looking back at today and being thankful for the discovery that has changed our field. But for now, we need to use every weapon in our armamentarium against IBD so that we can stay ahead of these diseases as opposed to chasing them.


About the Author

Corey A. Siegel, MD, MS, is the Constantine and Joyce Hampers Professor at the Geisel School of Medicine at Dartmouth. Dr. Siegel also holds multiple positions at the Dartmouth-Hitchcock Medical Center including Section Chief of Gastroenterology and Hepatology and Co-Director of the IBD Center. Dr. Siegel is also Co-Chair of the IBD Qorus Quality Program for the Crohn’s and Colitis Foundation (CCF).  

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