[00:29]
Hello, I’m Dr. Jami Kinnucan 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.
Thank you for joining me in this discussion of treat-to-target approach in inflammatory bowel disease (or IBD) as well as monitoring of disease after treatment initiation.
During this presentation, we’ll focus on the importance of treatment targets in IBD, their relation to disease modification, and the ways to monitor IBD during treatment.
[00:58]
We’ll first review what treat-to-target strategy is and why it’s important when treating patients with IBD.
In 2021, the International Organization for IBD (IO-IBD) Selecting Therapeutic Targets in IBD, STRIDE-2 guidance was published and this provides a definition of treat-to-target strategy in IBD consisting of short-, intermediate-, and long-term goals based on symptoms, biomarkers, endoscopic healing, and overall well-being.1,2
This infographic outlines a treat-to-target strategy for IBD based on patients with active inflammation and presumed active symptoms.1
Applying this to my own practice, utilizing the treat-to-target strategy in IBD requires the personalization of a patient’s therapy plan according to their risk, comorbidities, patient preference, previous drug exposure and responses, as well as overall efficacy and safety of a specific treatment.3
[01:51]
Patients are monitored by assessing for clinical symptoms, cross-sectional imaging, biomarkers of inflammation, and patient-reported outcomes.1
Assessment for overall clinical response is followed by clinical remission and normalization of a biomarker, like C-reactive protein (or CRP).2
When initiating therapy, the treat-to-target strategy helps us define our immediate and intermediate targets, such as clinical response and clinical remission, respectively.2
There are also long-term targets including endoscopic healing, normalized quality of life, and absence of disability.2
The STRIDE-2 guidance recommends a treat-to-target strategy in IBD.1
It highlights newer modalities in monitoring disease, including intestinal ultrasound.2
It is important to note that the targets of transmural healing in Crohn’s disease (or CD) and histological healing in ulcerative colitis (or UC) are not considered formal treatment targets, according to STRIDE-2.2
[02:47]
Rather, these targets should be used as adjuncts to endoscopic remission, which represents a deeper level of healing.2
The goal of treat-to-target strategies is to avoid long-term disease progression through appropriate therapy in patients and regular monitoring.4 This helps adjust therapy so that therapeutic targets can be met.
The treat-to-target strategy identifies the importance of regularly assessing objective response to treatment.1
More importantly, it highlights the need for proactive monitoring to optimize therapy when targets are not being reached.1
It’s essential to recognize that IBD patients, as per the guidance from the STRIDE committee, require constant and continuous monitoring to ensure these targets.5
The turbo treat-to-target monitoring strategy recommends proactive monitoring every 2 to 3 months to ensure ongoing management and response evaluation.1
[03:35]
Prevention of disease progression through early inflammation control is crucial.1
However, there is a lack of agreement on how disease progression should be defined in IBD trials.4
The Selecting Endpoints for Disease-Modification Trials (or SPIRIT) initiative, under the authority of the IOIBD, had the objective of achieving an international expert consensus on endpoints to utilize in the future IBD disease-modification trials.4
Recommendations for outcome measures are divided into three sections4:
Impact on patient’s life (including health-related quality of life, disability, and fecal incontinence)
Midterm complications (comprising bowel damage, IBD-related surgery, IBD-related hospitalizations, disease extension, extraintestinal manifestations, permanent stoma, and short-bowel syndrome)
And long-term complications (defined by dysplasia or cancer, as well as mortality)
[04:31]
Now, let’s review specific treatment targets as recommended by STRIDE-2 for the management of IBD.
Like the biomarkers used for diagnosis and monitoring, many of the same biomarkers and clinical assessment tools are used at baseline and throughout disease management to assess change.2,6
We will explore various targets: Clinical, biomarker, and imaging modalities including endoscopy and histologic scoring.2
When selecting a therapeutic plan, consider factors such as disease severity, medication safety profile, and patient and payer preference.7
Post-initiation of treatment, assessment of response to therapy is used to ensure patients are improving symptomatically.1 The time it takes to achieve goals like clinical response and normalization of biomarkers depends on the specific therapy being used.2
[05:17]
Utilizing patient-reported outcomes in addition to objective measures like laboratory results are important to improve medical care.8
Examples of these tools include patient reported 2-item (PRO2) and 3-item (PRO3). These tools are used in Crohn’s disease and ulcerative colitis.2,8
PRO2 and PRO3 cover stool frequency, the presence of abdominal pain, rectal bleeding, and the patient’s general well-being.8 The PRO2 is standard for assessing symptoms.2
Other patient-reported outcome tools include the IBDQ for quality of life, PSQI for sleep quality, and PHQ-9 for depression.8
There is also the PROMIS initiative, which developed ways to measure PROs across many chronic diseases, including health-related quality of life.9
The choice of which PROs to use in the electronic health record or documentation depends on your practice. Many of these assessments are web-based, and can save time and resources for the clinician.8
[06:10]
It is imperative to emphasize that establishing patients’ baseline is as important as monitoring their disease, so you can gauge whether or not they have objectively improved, and to guide treatment selection.1
The most comprehensive measures for disease activity available are the Crohn’s Disease Activity Index (or CDAI) for CD, and the Mayo score for UC.8
Other scoring tools, including the Harvey-Bradshaw Index in CD and the partial Mayo Score in UC, help define goals like clinical response and remission.1
Following patient clinical response, according to STRIDE-2 treat-to-target strategy, we should aim for symptomatic remission and normalization of CRP and fecal calprotectin (or FC).2
CRP is the main serum biomarker used for monitoring inflammation in IBD.1
CRP has a short half-life, 19 hours, and will rise and decrease rapidly at the onset and resolution of inflammation.1
It is important to remember, however, that over 15% of patients may not have an elevated CRP level.1
[07:09]
STRIDE-2 currently recommends that normalization of CRP, to the values under the upper limit of normal or less than 5 milligrams per deciliter, should be a mandatory short- to medium-term target goal.1,2
Endoscopic healing, a long-term treatment target, can be assessed by sigmoidoscopy, colonoscopy, or other methods such as capsule endoscopy or balloon enteroscopy.2
Endoscopic healing should be measured by Simple Endoscopic Score for Crohn’s disease (or the SES-CD) and Mayo endoscopic subscore or ulcerative colitis Endoscopic Index of Severity (UCEIS).2
Transmural healing may be assessed using various imaging modalities, such as CT enterography, MR enterography, and intestinal ultrasound.2
Again, while not a formal treatment target in CD or UC, transmural healing may be used as an adjunct to endoscopic remission, representing a deeper level of healing.2
Video capsule endoscopy may want to be considered for cases with more isolated small bowel disease.1
[08:09]
It’s important to remember that any of these modalities can be paired with CRP or fecal calprotectin, a non-invasive stool marker.10
Fecal calprotectin is a calcium-binding protein that consists of a complex formed by two proteins, S100A8 and S100A9.6 It is derived primarily from neutrophils and has a role in innate immune response. Calprotectin is stable at room temperature for several days.
Fecal calprotectin has a high correlation with clinical disease activity as well as endoscopic and histologic indices.2
It is effective in detecting colonic or ileal colonic disease, as well as cases of isolated small bowel disease.6,11
Additionally, fecal calprotectin can be used at baseline and in routine practice for follow-up.1
It is a better study for looking at colonic or ileal colonic disease than for patients with isolated small bowel disease.12
[09:01]
The other thing that comes up when monitoring patients is the appropriate timeline to consider evaluating therapies.1 We have to be able to assess response monitoring, which does not just mean asking about clinical symptoms. Many patients will start to feel better, but they might still have ongoing objective inflammation, and so you’ll have to be able to capture that.
This could mean using CRP in the majority of patients for monitoring. And in order to do this, you have to understand where their baseline was to assess change.11 You could utilize fecal calprotectin as well, but it is important to understand that there are various different cut offs that can be utilized for monitoring.
Also consider follow-up imaging modalities, either CT or MR enterography.11
With endoscopy, the STRIDE guideline recommends endoscopic assessment 3 to 6 months after starting therapy for UC, and 6 to 9 months after initiating therapy for CD.13
And then of course we have the opportunity to consider the use of intestinal ultrasound in our practice and where this might fit into monitoring strategies.11
[10:00]
When to monitor therapy is an important consideration.
Monitoring response to therapy is important not only to insure symptomatic improvement but objective improvement in intestinal inflammation as well.1
According to the AGA and ECCO-ESGAR guidelines, the evaluation and reevaluation of CRP and fecal calprotectin is recommended after 2 to 6 months based on the clinical context to predict further disease progression while utilizing most therapies.14-16
Additionally, according to the ECCO-ESGAR Diagnostics guideline, endoscopic or transmural response to therapy should be evaluated within 6 months after therapy initiation or optimization.14
Consideration should also be given to the potential role of intestinal ultrasound in monitoring strategies since it is preferred by some patients over invasive modalities.11
Intestinal ultrasound has demonstrated value beyond diagnosis and has utility in disease monitoring and treatment management in the treat-to-target era.17
[10:55]
In Crohn’s disease, intestinal ultrasound can be used to assess healing to determine whether treatment should be changed or continued.18 It can detect potential complications like strictures and abscesses as well as be used to evaluate treatment response after initiating steroids or biologics.19 Intestinal ultrasound can also be useful in ulcerative colitis.18 To evaluate treatment response, intestinal ultrasound can be used to measure bowel wall thickness and assess for transmural healing after treatment initiation.19
However, it’s important to acknowledge areas of uncertainty.19 The role of intestinal ultrasound as a monitoring tool has not yet been standardized, nor is there a consensus definition for intestinal ultrasound response. There remains a need for more robust trials and clearer guidelines on its optimal utilization.
[11:41]
Surgical intervention is a common aspect of managing Crohn’s disease.20 According to a 2021 meta-analysis of 22 population-based cohort studies, the cumulative risk of undergoing the first major abdominal surgery within 10 years of diagnosis is approximately 40% in patients with Crohn’s disease.
Post-surgery monitoring for Crohn’s disease activity is crucial and utilizes various modalities.21
The AGA recommends postoperative endoscopic monitoring at 6 to 12 months after resection.22
[12:09]
No matter what therapy plan you’ve decided for your patient, this slide provides an overview of some of the available testing modalities utilized post-surgery, including using fecal calprotectin and biomarkers, intestinal ultrasound, and the use of imaging modalities like CT enterography or MR enterography, and of course the role of colonoscopy post-surgery. The idea is to avoid monitoring too soon, as it may not capture potential recurrence. However, it is important to conduct post-surgery testing periodically after initiating a therapy plan.
So, let’s sum everything up in a treat-to-target monitoring algorithm.
It is important to note that IBD management aims for clinical and endoscopic remission, though different management scenarios necessitate personalized patient care.2
Our targets are clinical remission and ultimately endoscopic healing.1
[12:58]
After successfully attaining our targets of clinical remission and endoscopic healing in a patient, and they feel better symptomatically, we are going to keep them on a monitoring strategy.1
For patients who have had a clinical response or even achieved remission and despite that, continue to have a persistent elevation of their CRP or their fecal calprotectin with evidence of ongoing inflammation, there is an opportunity to optimize their therapy and reevaluate response.1
For patients who continue to have clinical symptoms of Crohn’s disease or ulcerative colitis, without objective evidence of inflammation, instead of optimizing their IBD therapy, there is an opportunity to discuss and treat other causes of symptoms unrelated to IBD.1
[13:40]
To illustrate the aspects of IBD monitoring we have discussed thus far, let’s review this turbo treat-to-target monitoring strategy developed by Plevris, and colleagues.1
At diagnosis or treatment initiation, it is crucial to establish a baseline assessment with blood and stool biomarkers matched to imaging for use as benchmarks.1
Once treatment is initiated, biomarkers can be used, monitoring proactively every few months regardless of clinical disease activity.1 If both biomarker and symptom targets are met, therapy can continue as is. If biomarker targets are not met, optimization of therapy is necessary.
In cases where biomarker targets are met but symptoms persist, non-inflammatory causes for symptoms should be explored.1
[14:25]
After 12 months of therapy, repeating baseline assessments, including endoscopy, should be performed to confirm achievement of long-term targets.1,7
Long-term targets include endoscopic remission, and future considerations involve achieving transmural healing in Crohn’s disease and histologic healing in patients with ulcerative colitis.
According to ECCO-ESGAR Diagnostics guideline, imaging allows for personalized approach to patient care and monitoring of IBD after initiating therapy.1,14
Cross-sectional imaging, including CT enterography, MR enterography and intestinal ultrasound, have a key role in assessment before, during and after treatment in Crohn’s disease.23
[15:05]
The use of intestinal ultrasound to assess disease activity is becoming widely available and its use is gaining popularity.1,2 In the last few years, there have been growing utilization of cross-sectional imaging techniques for assessing IBD.24 CT enterography and MR enterography can be useful for assessing Crohn’s disease activity, and bowel ultrasound can help with detecting post-surgical recurrence. The use of cross-sectional imaging has increased for ulcerative colitis as well in the form of intestinal ultrasound, which has demonstrated accuracy in detecting colonic inflammation in ulcerative colitis.
Imaging methods such as MR enterography can provide disease information by revealing post-treatment anatomical changes.23
This could enable a more personalized approach to patient care, allowing for tailored strategies based on the specific therapy plan.1,2
[15:50]
Compared with other cross-sectional imaging modalities, intestinal ultrasound is non-invasive, rapidly available, requires no preparation, involves no radiation, provides expedient results, and has a low cost.11
Additionally, point of care ultrasound can enable earlier changes in treatment.25
This modality could gain broader acceptance with increased training.26
Notably, intestinal ultrasound directly reflects transmural disease activity, making it a valuable tool.11
IBD monitoring strategies have evolved over time, transitioning from relying solely on patients’ symptoms to incorporating more objective testing and non-invasive monitoring strategies.26
While current modalities include cross-sectional imaging, future opportunities may exist in novel biomarkers related to fibrostenotic disease or fibrosis-related imaging.25
Artificial intelligence is an emerging and potential tool for enhancing monitoring strategies and reducing variability.25
[16:43]
In my opinion, IBD monitoring is just like IBD treatment. It needs to be personalized to the patient in front of you, which means considering what their needs and desires are, and what their symptoms may or may not be.1,26
If you don’t do C-reactive protein monitoring, CRP is going to add little value to what therapy plan you selected. In my practice, I might look sooner and monitor sooner in a patient that I use either steroids or a JAK inhibitor as opposed to a patient that I might use a therapy that may have a more delayed onset in terms of inducing remission.
The landscape of IBD monitoring is continually evolving. I recommend staying abreast of current guidelines and consensus recommendations regarding the use of imaging in monitoring as this will help you to provide optimal care for your patients.
[17:28]
A study assessing the preferences of 916 patients for IBD monitoring strategies showed patients are more accepting of serum and fecal biomarkers, capsule endoscopy, MR enterography, and intestinal ultrasound compared with other endoscopic procedures.27
Intestinal ultrasound is a widely preferred option due to its non-invasiveness, efficiency, affordability, and point-of-care evaluation capabilities.11,25,27
Venipuncture is also considered favorable by patients; it’s used to monitor CRP and other lab abnormalities such as anemia, or iron deficiency.27,28
Patients with Crohn’s disease expressed a preference for capsule endoscopy over methods like stool collection, colonoscopy, or flexible sigmoidoscopy.27
[18:10]
So far in our program we have discussed approximate timing for monitoring and reassessment of mucosal healing, but the exact timing may depend on the clinical necessity and particular therapy.14
It is important to note that there is no single approach for all patients. The expanding therapeutic landscape necessitates identification of biomarkers to predict therapeutic response or therapy-specific complications.29
Implementing a monitoring strategy is a multidisciplinary effort; clinicians need a clear understanding of the baseline assessment and when to assess treatment response, symptom check-ins, and testing schedules.1,30
Care of patients with IBD can be complex.30 The multidisciplinary team should include at least: a gastroenterologist, a surgeon, a radiologist, a pathologist, an IBD-specialized nurse, a dietician, and a pharmacist.
[19:01]
Of equal importance is patient understanding and buy-in; maintaining open communication with patients and effective shared decision-making may help with treatment satisfaction and improved adherence.7,30,31
I hope you enhanced your knowledge about these principles that can be integrated into your practice.
Thank you for your interest and spending time with IBDIQ today to help adapt to the evolving care needs of all IBD patients.
