The PRECIOUS Study: Predicting Crohn’s and colitis Outcomes in the United States

PRECIOUS is an observational study investigating the ability of a prognostic biomarker, called PredictSURE® IBD, to predict long-term outcomes in inflammatory bowel disease (IBD) patients.  PredictSURE IBD is a whole-blood biomarker test that can be performed at diagnosis and stratifies patients as high- or low-risk based on their risk of requiring multiple treatment escalations – a feature of aggressive disease.  The biomarker was developed by researchers at Professor Ken Smith’s laboratory at the University of Cambridge (UK) and validated in a UK patient cohort¹.  The PRECIOUS study seeks to extend that validation to the more ethnically diverse US population.

What’s so exciting about a prognostic test for IBD?

We’ve previously discussed the background of the test and why it’s important in our blog about the PROFILE study, so here are the key points:

• IBD is an incurable disease that causes inflammation of the digestive tract, leading to symptoms such as abdominal pain, diarrhoea and fatigue.
• Both Crohn’s disease and ulcerative colitis (the two main forms of IBD) are typified by their relapsing-remitting disease course.
• Disease course and response to treatment are highly variable from patient to patient.

Figure 1. illustrates the variability in IBD progression, with two patients who presented with very similar clinical results who went on to experience very different disease courses, requiring different therapeutic interventions and resulting in different outcomes.  PredictSURE IBD provides a means of differentiating between these two patients: the disease course of the top patient is consistent with low-risk classification and the bottom patient who has more frequent flares, is consistent with the high-risk category.

Figure 1:  Case studies from two patients diagnosed with Crohn’s disease, illustrating the variability of disease course from patient to patient.

In the absence of a prognostic test like PredictSURE IBD, that predicts long-term disease course, treatment cannot be tailored to an individual patient’s likely disease course.  As a result, patients are typically treated in one of two ways:

• Top-down: starting with the most aggressive therapies (and typically the ones with the highest risk of side effects) to get control of the disease as early as possible.
• Step-up: starting with the mildest therapies and escalating in response to continued or repeated disease activity

Neither approach is ideal when you’re dealing with patients as different as those illustrated in Figure 1.   Whilst the top-down approach provides the best opportunity to achieve remission in high-risk patients, it risks over-treating low-risk patients who may otherwise have had a more quiescent disease course.  Conversely, with a step-up approach you risk undertreating high-risk patients, which can result in bowel damage, increased risk of surgery and a poorer quality of life.

A reliable prognostic test allows gastroenterologists to differentiate between high- and low-risk patients, enabling them to tailor treatment choice to an individual patient’s likely disease course (Figure 2).  While no prognostic test is 100% accurate, PredictSURE IBD outperforms other current methods such as clinical markers of severity.  As such, PredictSURE IBD offers an additional tool to help gastroenterologists and patients select the best treatment for their individual risk profile.

Figure 2: How we envisage the PredictSURE IBD test being used to help identify the best treatment course for individual patients based on their likely disease course.

Why is the PRECIOUS study important?

PredictSURE IBD was originally shown to reliably identify high- and low-risk IBD patients at 4 UK sites.  This patient group was ~90% Caucasian, so we were keen to ensure that the test is effective in a more diverse patient population.  We chose North America for its diversity and also because we wanted to give US and Canadian clinicians a chance to become familiar with the test to support its uptake when it is approved for clinical use in the United States.

We successfully applied to the Crohn’s & Colitis Foundation for support to fund the study and are grateful to the Foundation for their ongoing support.

How is the study going?

The PRECIOUS study started recruitment in early 2019 under the guidance of our two Chief Investigators: Dr James Lee and Dr Lea Ann Chen.  PRECIOUS is recruiting at 15 sites:

• Northwell, Health Inc, PI: Dr Keith Sultan
• University of Southern California, PI: Sarah Sheibani, MD
• Rutgers Robert Wood Johnson Medical School (pediatric), PI: Dr Melissa Weidner
• Rutgers Robert Wood Johnson Medical School (Adult), PI: Dr Lea Ann Chen
• John Hopkins Medical Center (pediatric), PI: Maria Oliva-Hemker, MD
• NYU Langone/Bellevue, PI: Dr Jordan Axelrad MD
• Weill Cornell, PI: Dana Lukin
• NYU Winthrop, PI: Bradley Morgenstern, MD
• University of Rochester, Medical Center, PI: Dr. Saubermann
• University of Miami Crohn’s and Colitis Center, PI: Oriana Damas, MD
• UCLA Center for IBD, PI: Jenny Sauk, MD
• Mount Sinai Hospital (Toronto), PI: Ken Croitoru, MD
• Washington University in St. Louis, PI: Dr Deepak Parakkal
• Manhattan Clinical Research, LLC., PI: Dr Caterina Oneto
• Johns Hopkins IBD Center for Adults, PI: Brindusa Truta, MD

Who can participate?

We are seeking patients with a new or recent diagnosis of Crohn’s disease or ulcerative colitis who are biologic-naïve and who have active disease.

• Patients cannot be on steroids at the time of blood draw and must be steroid free for at least 7 days prior to blood draw
• Patients must be experiencing a flare or period of active disease
• Patient cannot be scheduled to start biologics as first line therapy

Despite the Covid pandemic and its impact on all studies, we are proud to have recruited 126 patients and are grateful for the hard work and dedication of our study teams and our intrepid study recruits.

What’s next?

Recruitment will continue until the end of March 2023, so if you or someone you know has a recent IBD diagnosis and is being treated at one of our sites, please check out the PRECIOUS website to find out more.

You can also contact Karen Hills or Lediona Ardolli for more information.