[00:30]
Hello, I’m Dr. Ryan Ungaro and welcome to IBDIQ, part of The IBD Project by Takeda, where we’re coming together to help enhance expertise in IBD care—right from the start.
Today, we’re going to discuss factors associated with the progression of inflammatory bowel disease (or IBD). We’ll start by overviewing IBD disease progression and complications, including the implications of delayed IBD diagnosis. Next, we’ll define disease activity and severity factors. And then, based on these and other prognostic factors, we will review how patients may be stratified by their risk of progression through using risk assessment tools.
Let’s get started.
[01:06]
IBD, which includes Crohn’s disease (or CD) and ulcerative colitis (or UC), is a chronic and progressive disease of the intestinal tract.1
As a progressive disease, the subclinical inflammation associated with Crohn’s may lead to various complications.2-4 These may include fistulae which are abnormal connections between epithelial surfaces, like the skin and the anus; strictures, which happen when scar tissue leads to a narrowing of the intestine; perianal abscesses, which are collections of pus near the anus; and colorectal cancer.4-8
Growing evidence suggests that early treatment of Crohn’s may be favorable.4 We’ve come to recognize a potential ‘window of opportunity’ after diagnosis, where if we treat inflammation effectively, then we may be able to prevent long-term complications such as strictures, fistulae, abscesses, and surgery.
[01:55]
In UC, subclinical inflammation and disease progression have been associated with complications, including structural and functional abnormalities.2,9,10 Structural abnormalities may include bridging fibrosis, or connecting bands of accumulated scar tissue in the intestine, strictures, and pseudopolyps.9-13 Neoplasia, or tumors resulting from abnormal tissue growth may also occur.11,14
Functional abnormalities may include increased colonic permeability, leading to a leaky intestinal lining, and decreased contractility, or weakened intestinal movements.9-11 Rectal dysmotility, or changes in how the rectum moves and adapts to pressure, may also occur.9,10
A 2023 systematic review and meta-analysis based on 31 population-based and cohort studies provides insight on one of the challenges associated with UC over time.15 The study assessed the risk of colectomy at various time intervals following a UC diagnosis.
In Years 1 through 5, the risk of colectomy was between 3% and 5%.15 By Year 10, the risk rose to 10%, and by Year 20, the risk was 14%.
[03:00]
Conveying the increase in colectomy risk over time may help patients with UC understand their disease's potentially progressive nature and support more timely intervention.4,9
So, you may be wondering, “What determines whether a patient with IBD will experience disease progression?” To answer this, we first need to explore 2 concepts: disease activity and disease severity.
Disease activity reflects the state of inflammation at a single point in time.16 In contrast, disease severity captures the bigger picture of the impact of the disease on the patient over time.
Understanding these differences may be particularly relevant if a patient has low disease activity at a specific time, but their clinical history suggests a high disease severity.16
There are a variety of monitoring tools which may offer insights into the level of Crohn’s and UC disease activity.17 They may be based on clinical symptoms, imaging techniques, endoscopy, and biomarker assessment.
[03:57]
The patient-reported outcome 2 (or PRO2) is a tool that assesses clinical symptoms in both Crohn’s and UC.18 The Harvey-Bradshaw Index (or HBI) and Crohn's Disease Activity Index (or CDAI) evaluate activity in Crohn’s only. The partial and full Mayo score, as well as the Simple Clinical Colitis Activity Index (or SCCAI), are used specifically in UC.17,18
Imaging techniques to assess inflammation in both diseases include: computed tomography enterography (or CTE), magnetic resonance enterography (or MRE), and bowel ultrasound.17,18 Endoscopic and histological assessments may utilize sigmoidoscopy and colonoscopy.17-19
Endoscopic assessment is another component to evaluating disease activity.20 In Crohn’s, disease activity can be assessed using endoscopic indices such as the Crohn’s Disease Endoscopic Index of Severity (or CDEIS) and the Simple Endoscopic Score for Crohn’s Disease (or SES-CD).17,18 UC-specific assessments include the Mayo endoscopic subscore and the Ulcerative Colitis Endoscopic Index of Severity (or UCEIS).
[05:05]
Biomarkers are also utilized in disease activity monitoring for both Crohn’s and UC. These may include C-reactive protein (or CRP), fecal calprotectin, and erythrocyte sedimentation measurements (or ESR).17,18
And what about measuring a patient’s disease severity?
As mentioned earlier, IBD severity reflects the long-term impact on the patient, incorporating factors related to overall prognosis.16
Accordingly, it is measured using a combination of variables, including clinical disease severity factors, serology, and genetic biomarkers.16
Key clinical factors associated with disease severity for both types of IBD include, but are not limited to, the extent of anatomic involvement, age and potential delay of diagnosis, and the need for systemic steroids.16
More severe Crohn’s is associated with a history of smoking, and having perianal, stricturing, or penetrating disease.16 In contrast, UC disease severity is impacted by the presence of certain concurrent infections, like Clostridium difficile and cytomegalovirus.
[06:09]
Certain blood serology types—which indicate the presence of antibodies to certain bacteria or particles—may also contribute to assessments of IBD severity.16
Serology results that are positive for anti-neutrophil cytoplasmic antibodies (or ANCAs) and anti-CBir1 microbial flagellin protein (or CBir), are both associated with severe disease in Crohn’s.16 Although limited, there is some evidence for their implications in UC.16,21,22
The presence of anti-Saccharomyces cerevisiae antibodies (or ASCAs) or antibodies against granulocyte-macrophage colony-stimulating factor (or anti-GM-CSF) is currently only associated with disease severity in Crohn’s.16
Mutation in genes like NOD2, an immune-regulating gene associated with defense against and tolerance to pathogens, may also indicate Crohn’s severity.16,23
NOD2 mutation has been associated with severe Crohn’s as well as ileal involvement and increased risk of surgery.16,23,24
[07:04]
At this time, there is limited clinically practical evidence of associations between specific genetic variations and disease severity in UC.25-27
So, how do we integrate disease activity and severity assessments into an overall prognostic assessment of disease progression? Let’s explore this through the lens of each disease.
In 2014, the American Gastroenterological Association (or AGA) published their perspective on which patients with Crohn’s may be at a moderate to high, or low risk of, progression.28 In 2015, they published a companion piece for UC.29 I will refer to these publications as the AGA Care Pathway for CD and UC, respectively.
The AGA Care Pathway for Crohn’s notes that patients with Crohn’s may have a moderate or high risk of progression for several reasons: if they were diagnosed before the age of 30, had extensive anatomic involvement, deep ulcers, prior surgical resection, perianal or severe rectal disease, and stricturing or penetrating disease behavior.28
[08:06]
In contrast, it states that patients with Crohn’s may be at a low risk of progression if they were diagnosed after the age of 30, had limited anatomic involvement, no perianal or severe rectal disease, superficial ulcers, no prior surgical resection, and no signs of stricturing or penetrating disease behavior.28
Now let’s look at the AGA Care Pathway for UC, which stratifies patients by their risk of colectomy.29
According to this pathway, patients with UC may be at high risk if they were diagnosed before the age of 40 and had extensive colitis, deep ulcers, and/or other indicators, including the elevation of certain biomarkers, a history of hospitalization, steroid-requiring disease, or certain infections.29
The AGA Care Pathway for UC notes that patients may be at low risk of colectomy if they exhibit limited anatomic involvement and mild endoscopic disease.29
Physicians should consult updated guidelines when considering factors related to progression risk.29
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Let’s now explore the IBD Clinical Decision Support Tool (or IBD CDST), a no-cost, web-based tool for risk stratifying patients with either UC or Crohn’s which was endorsed by the AGA in 2022.30,31
This tool collects the patient’s demographic information, such as age, gender, ethnicity, race, and disease type.30,31
It evaluates disease burden through a series of questions.30,31 For Crohn’s, the questions are about anatomic involvement, perianal disease, rectal disease, presence of deep ulcers, history of surgical resections, stricturing behavior, and penetrating behavior.
For UC, the tool evaluates the presence of extensive colitis and/or deep ulcers, whether the patient has high CRP, their disease requires systemic steroids, and if there is a history of hospitalizations.30,31
[09:55]
The IBD CDST then provides an assessment about whether the patient is at high or low risk of developing complications with additional questions intended to support disease management planning.30,31 The IBD CDST may thus support physician selection of appropriate therapies based on their patient’s risk.
Limitations include that the CDST was not tested across all countries or health systems and does not incorporate patient preferences.30,31 Provider-patient conversations may additionally help clarify the tool's guidance.31
Let’s explore another method of assessing the potential risk of progression for a patient with Crohn’s specifically.32 Namely, a personalized prognostic tool called CDPATH.
CDPATH shows eligible adult patients with Crohn’s their potential individualized risk of developing a serious complication within a 3-year period.32,33 These may include development of bowel strictures, internal penetrating disease, or non-perianal surgery like bowel resection or stricturoplasty.
[10:55]
CDPATH is provided at no cost to patients who meet the following eligibility criteria: They are 18 years or older and were diagnosed with Crohn’s within the last 10 years.32
They have not yet experienced serious complications (defined as bowel strictures, internal penetrating disease, or non-perianal surgery).32 And patients must also be commercially insured or uninsured. Full eligibility terms and conditions are available at CDPATH.com.
CDPATH's advanced algorithm looks at specific patient characteristics, serologic factors, and a genetic factor to assess a patient’s individualized risk profile.32,33
Patient characteristics included in the model are: time from diagnosis—which helps confirm eligibility and also provides the baseline hazard function—and the disease location, which can help determine the likelihood of serious complications.32,33
Serologic factors also contribute to CDPATH predictions of the course of disease.32,33 Specifically, the model accounts for results from assays detecting ASCA, pANCA, and CBir1 antibodies.
Finally, the CDPATH model looks at a specific variant of NOD2, a genetic factor that may help identify the likelihood of serious complications.32,33
[12:05]
These selected clinical measures are good predictors of a diagnosed adult patient’s potential risk of developing serious Crohn’s complications within 3 years.32 However, not all known variables are incorporated; thus, CDPATH should be considered in conjunction with other relevant clinical assessments.
The CDPATH report provides results from the model’s components.32 The report also includes a graphical depiction of whether a patient is potentially at low, medium, or high risk of developing a serious Crohn’s complication.32,33 This visual approach may help patients better understand their disease and individual risk profile, which may promote more proactive collaboration with their care team around disease management.
Results should be interpreted alongside a comprehensive clinical assessment and a provider-patient discussion.32,33 CDPATH is validated only in the U.S. and the model has not been tested or established in patients who already had surgery or experienced a complication. Full details regarding the development of the model, its validation, and limitations are available on CDPATH.com.
[13:06]
Now that we've discussed IBD progression and the importance of risk stratification, let's take a moment to review the key points we've covered today.
IBD is a chronic and progressive inflammatory disease for which timely intervention may help prevent progression and associated complications.1,2,4,9
Factors associated with IBD disease activity and severity may contribute to a prognostic assessment of progression risk.16
Available risk stratification tools may provide clarity on a patient's potential IBD prognosis.30,32
And finally, risk stratification tools may support shared decision-making conversations between the care team and patient.30,32
Thank you for your interest and for spending some time with IBDIQ today to help adapt to the evolving care needs of all patients with IBD.
