Seeking better biomarkers and indicators of IBD
Published: March 30, 2020
When Christopher Columbus first sighted land in October 1492, he thought he had reached Japan. That’s how bad his map was.
In medicine, we rely increasingly on biomarkers (indicators of disease) to ”map” our health, disease risks, disease conditions, and responses to treatment. Some biomarkers are often part of our everyday conversation, like cholesterol, blood pressure, and iron levels. A biomarker is a defined and measurable characteristic that help to track our health or disease. Think of them as ‘snapshots’ that help guide diagnosis or treatment decisions.
Are they reliable? Yes, if they’re validated, meaning that they’ve been tested in patients and shown to consistently link with clinical outcomes or conditions.
A Foundation priority: Accelerating the development of IBD biomarkers
We urgently need better and more IBD biomarkers to help answer critical questions, including diagnosis (“is this really Crohn’s disease or ulcerative colitis or something else?”); prognosis (“am I at high risk for more severe disease?”); therapeutic prediction/precision medicine (“Am I more likely to respond to drug A or drug B?”); and monitoring (“Is this an IBD flare or a virus?”).
Currently, we rely on procedures, like colonoscopy, to help diagnose and evaluate IBD. This procedure is very helpful, but also invasive, expensive, and carries some risk. They don’t answer all of our questions.
We also have two less invasive biomarkers in clinical use today:
- C–reactive protein (CRP), obtained through a simple blood test, measures inflammation. However, CRP doesn’t tell us whether the inflammation is linked to IBD or might be caused by something else (like a bacterial or fungal infection).
- Fecal calprotectin (FCP), a protein obtained from fecal samples that is more specific to the colon and can help tell whether there’s inflammation in the colon. But many patients dislike giving fecal samples, which is an important consideration.
We need better biomarkers.
That’s why the Foundation convened its second annual IBD Biomarker Summit at the end of last year. Our first Biomarker Summit, held in 2018, marked the first-time stakeholders from academia, industry, nonprofit organizations, patient advocates, and regulatory agencies came together to focus on IBD biomarkers. That meeting was conceived and led by the Foundation and helped to identify critical unmet needs and how these groups might work together.
This year, we heard updates on biomarkers in development and strategized about how to break down barriers and make more progress faster.
In this blog post, we’ll share what’s in the development pipeline, next steps, and what it means for you.
The Foundation as Catalyst: Bringing everyone to the table
Have you ever had problems switching between a Mac and a PC? Or upgrading to a new operating system for your cellphone? Ever find that they don’t talk to each other? New products may be innovative, but they often don’t translate well across brands or systems. We have the same problem in medicine.
As Dr. Anthony Samir from Massachusetts General Hospital and Harvard Medical School noted, “We use several different radiological instruments from several manufacturers who don’t normally collaborate. Everyone has their pet biomarkers [and] conflicts of interest and they stay in their own worlds. The Foundation has an important convening function to [enable] these discussions, which can lead to a more constructive competition.”
Dr. Diana Merino, a science policy analyst with Friends of Cancer Research, added, “Part of our job [as a non-profit] is to build trust [and] to turn competitors into ‘frenemies’ so that we can all work more productively. It’s not easy but it’s essential.”
The Foundation's Biomarker Summit brought together over 90 people from academia, industry, foundations, patient advocates, and government regulatory bodies such as the FDA. The Foundation also conducted interviews prior to the meeting with a wide range of stakeholders, including patients and caregivers, to make sure that their concerns were part of this agenda.
Biomarker Summit Highlights: What’s new and upcoming
Much of the Summit was devoted to sharing ideas on identifying key biomarker targets and strategies to accelerate research and development. But we also heard from researchers in several areas about new products in various stages of development. Here are a few highlights, covering new, less invasive concepts for blood tests, urine tests, and imaging:
- PredictSure IBD™, now available in the UK and Europe, is the first biomarker that can help guide personalized medical treatments for new IBD patients. Using just a blood test, this biomarker can reliably predict the risk of severe disease in newly diagnosed patients. This development is so important that the Foundation is supporting the U.S. clinical study for PredictSure IBD™. If it works as well here as it did in the UK trials, this could be a game changer to enable better-informed treatment decisions.
- Why this matters: PredictSure IBD™ is a non-invasive biomarkers that can help identify patients at high-risk for severe disease, which opens the door to more personalized treatment strategies for high-risk patients.
- Where it stands: Commercially available in the UK, and currently recruiting patients for U.S. study.
- PGE-MUM is a new urine test for ulcerative colitis (UC), now in development in Japan, which has the second largest population of UC patients in the world. As Dr. Mayasuki Saruta explained, the two current tests have limitations; fecal samples “are cumbersome and embarrassing for our patients to handle” and CRP tracks inflammation but can’t tell us whether there is healing of the intestinal wall (mucosal healing) in UC patients. So, they’ve worked hard to develop a more patient-friendly test that also can assess mucosal healing. Their product, PGE MUM, targets a urinary metabolite (a substance produced during digestion or other bodily chemical processes) that has been shown to do a better job of predicting mucosal healing in UC than the CRP test.
- Why this matters: Mucosal healing is linked with better long-term outcomes (fewer recurrences and fewer complications). A patient-friendly and more accurate test can help physicians make better treatment decisions without having to conduct multiple invasive endoscopic procedures over a short period of time.
- Where it stands: Currently undergoing further studies in Japan; no testing as yet in U.S.
- Have ever you used Siri or Alexa, or even done a simple Google search to get information? If so, you’re already using artificial intelligence (AI) and machine learning (a type of AI, in which the computer and software teaches itself to recognize key patterns based on an enormous input of data). Right now, when it comes to IBD imaging, neither magnetic resonance nor ultrasound studies do a good enough job at differentiating inflammation (which needs treatment) from scarring (also known as fibrosis). Several teams from various academic centers are working to solve this problem with machine learning.
- Why this matters: Many imaging researchers think that AI and machine learning may produce more accurate readings of images than individual human radiologists. As one attendee noted,, “machines don’t get tired and need coffee breaks.”
- Where it stands: The potential of this technology is currently being evaluated in studies supported by the Foundation and the National Institutes of Health.
Biomarker Summit: Next steps
Much of the discussion at the Biomarker Summit focused on how best to accelerate research and development. Some of the ideas were built upon the 2018 Summit while others came out of the ‘spontaneous combustion’ of getting the right people together in the same room. Some examples:
Advancing biomarker qualification by the FDA
At the 2018 Biomarker Summit, the Foundation brought together the Critical Path Institute (a nonprofit organization dedicated to accelerating the drug development process) with multiple nonprofit, academic, and pharmaceutical industry collaborators active in the IBD field to identify key challenges and opportunities to developing better biomarkers to improve clinical trials. Now the Critical Path Institute is leading a pre-consortium (an informal work group) with members from industry, academic and regulatory agencies on a mission to get fecal calprotectin and additional biomarkers ready for the FDA qualification process, a rigorous process to establish how a biomarker can and should be used in the context of drug trials.
If the FDA has approved the significance of a specific biomarker, then when a clinical trial shows significant positive results and measures it with an approved biomarker, it may pass through the FDA approval process more easily. However, FDA qualification doesn’t necessarily mean that a test is available for clinical use or, for those tests that are available, that your insurance will pay for it. If you or your physicians are using laboratory tests to help with your treatment but are having problems with reimbursement, the Foundation has some sample appeal letters designed to help.
Including broad populations in research
At a special breakout session on special populations, clinicians and researchers focused on patient groups that often face lag times in product development, These include pediatric patients, older adults (over 65), and post-surgical patients who cannot yet be scoped. There’s a longstanding issue in medicine of testing mostly in adult populations, and leaving geriatric and pediatric patients behind. Attendees discussed out-of-the-box ideas to make sure these populations are included in clinical studies.
Special Inflammatory Bowel Diseases issue
The Foundation will be a dedicating a special issue of Inflammatory Bowel Diseases®, the official journal of the Crohn’s & Colitis Foundation, to IBD biomarkers in 2020. The issue will include an overview of take-home messages from the two Biomarker Summits, plus new articles designed to educate and advance this important area of research. The deadline to submit a paper for this special issue is April 24. Click here to learn more about submitting your research.
Biomarkers: the bottom line
Pharmaceutical companies are in the business of developing drugs, not biomarkers. Biomarkers are generally like Cinderella, an essential housekeeper in the background but not the star of the show. As one attendee at the Biomarker Summit noted, “biomarkers are a bonus, not the main course when it comes to drug development.” That‘s one reason nonprofit organizations and academia need to be engaged to help develop useful biomarkers.
PredictSure IBD™, the new prognostic biomarker in the UK was developed at an academic institution (Cambridge University) with support from the Wellcome Trust, a UK medical charity. The Crohn’s & Colitis Foundation is now supporting a U.S. study of the tool in order to accelerate its validation in our country.
None of this happens without you.
Your participation—as patients, caregivers, and patient advocates— is crucial, whether through engaging with the Foundation, giving feedback, sharing ideas, or participating in clinical trials. Dr. Mary-Louise Greer, radiologist at Children’s Sick Hospital in Toronto, spoke for many attendees when she said, “I hope patients understand that when they give samples—whether it’s for a biomarker study or another kind of study—they’re giving us multiple chances to develop better tools and treatments. Without their participation, we can’t move forward.”
We echo Dr. Greer’s point. You may or may not benefit directly from participating in a research study. But by participating, or donating samples during a routine colonoscopy, for example, you may be giving a gift that keeps giving for years.
If you’re interested in learning more about or getting involved with research opportunities, here are two easy ways to get started:
- Learn about clinical trials and search for one near you with our Clinical Trial Finder
- Join IBD Partners, answer surveys, and pose and/or vote on research questions
Sheila Roher, MPH, is a science writer for the Crohn's & Colitis Foundation.