PredictSURE® IBD and the PROFILE trial

PredictSURE® IBD and the PROFILE trial – a patient perspective

Imagine this situation, you get diagnosed with a lifelong medical condition and while specialised doctors can treat you when you are symptomatic, they cannot predict how severe the condition could or will get for you. It’s a scary prospect and this is where I was as an inflammatory bowel disease (IBD) patient almost a decade ago.

A significant period of my first six months of learning to live with Crohn’s disease – one of the main forms of IBD – was spent wrapping my head around just how much this was going to impact on my once healthy life. I can remember the frustration I felt when I found it hard to plan more than a couple months ahead and how I had to adjust to a new ‘normal’.

Statistics and ‘worse case scenarios’ were thrown my way and that did not comfort me in accepting my illness. No medical professional could predict or plan how my immune system would respond to the medications, stress, lifestyle changes or indeed adaptations I made to my diet; because IBD was still so unpredictable.
Things have moved on in the last 10 years, with increasing recognition that treating all patients in an identical way, without considering the future path of their disease (their “prognosis”) does not lead to the best outcomes. When I was diagnosed, I was treated in the standard way – the step-up approach – which means first being given steroids, and then waiting to see if they work. They didn’t, so I progressed to 5-ASA and then when that didn’t work biologics, which were effective. My experience since then hasn’t been great – unpleasant hospital admissions, multiple surgeries. It has left me wondering, had I gone straight on to biologic therapy, and achieved control of my disease early on, could I have avoided those admissions and maybe the surgery?

Predicting disease course

While clinical pathways that tell doctors how to approach to IBD treatment have been improved throughout the years as new medications have been discovered, tools for doctors to predict disease course and prescribe accordingly have remained unavailable. To make things better for patients, many doctors think that giving those at risk of more severe disease stronger medication first (the ‘top-down’ approach) is vital, which has given rise to a hunt for predictive ”prognostic” biomarkers.

One such biomarker was identified by clinical immunologist Kenneth Smith’s team, at the University of Cambridge. They found a genetic signature relating to ‘T-cell exhaustion’, a kind of immune dysfunction, which can affect how bad your IBD is. In IBD, where the body is in effect attacking itself, each person’s experience is dependent on the state of their own immune system. T-cell exhaustion is important because when in this state, the immune system is weakened, meaning less inflammation and a milder disease.

The potential of this gene signature, and evidence that it can accurately predict long-term disease outcome at the time of IBD diagnosis, led to the “spinning out” of start-up company PredictImmune from the University of Cambridge in 2017 to translate the biomarker into a prognostic blood test suitable for clinical use. Could this test truly answer the burning question: how bad will an individual patient’s IBD become?

The science – why the test matters

The blood test, called PredictSURE IBD, can tell you whether you are more or less likely to suffer multiple flare ups in the first year after diagnosis. Currently, standard treatment pathways are ‘one size fits all’ which can either under treat or over treat patients, as their disease course is unknown. This test could take away a lot of the guessing game that surrounds newly diagnosed patients with Crohn’s disease, leading to appropriate treatments, improved outcomes and improved quality of life. The test is already approved for use in the UK, but not yet available on the NHS, which is the ultimate goal.

Figure 1 PredictSURE IBD can predict who is at greater or lesser risk of severe disease. Knowing potential patient outcomes could help doctors choose treatments more effectively.

The PROFILE trial

Getting the NHS to start using PredictSURE IBD will partly dependent on additional clinical evidence of the impact of basing treatment on a patient’s prognosis. To find this out, PredictImmune are running the PROFILE clinical trial in collaboration with Cambridge University, Cambridge University Hospitals and with funding from the Wellcome Trust.

PROFILE has a broad inclusion criteria i.e. most patients with a new or recent (<3 months) diagnosis of active luminal Crohn’s disease aged 16-80 can be considered. There are some exclusion criteria to consider such as severe penetrating disease and complex peri-anal disease. It is also worth considering that when patients who sign up to PROFILE, do not get given the results of their test (to avoid skewing results), and the treatment they get might be either step-up or top-down as this is randomised in the trial. If you think you are eligible and are interested in signing up to PROFILE, you can find out more here.

Why is the PROFILE study important?

It will support the wider use of the test, which is invaluable to patients – allowing them to make more informed treatment decisions with their doctor, and to take more responsibility for their disease, allows them to plan better for the future
The potential for long term lower costs for the NHS. The test is a currently a one off payment at the beginning of a patients journey with IBD. But ultimately it could be cost saving as it could prevent unnecessary medications, surgery and overall potential disability. With the changing landscape of moving to more remote appointments, it could be that doctors can be more confident in monitoring low-risk patients less frequently with the results of this test.
It will help provide more evidence to assess whether treating patients with a more personalised approach – the study randomises patients for a ‘top down’ or ‘step up’ treatment pathway – is beneficial.,. For the future, it is hoped that this test takes the guesswork out of drug selection for people with IBD. And this could be the difference between patients receiving unnecessary medications and being able to correctly treat with the right and most appropriate pathway

Latest study update (January 2021)

Currently the study is running at ~40 sites across the UK.
About half of these sites have now re-opened since the first COVID lockdown.
It is expected that sites will continue to recruit as best as possible.

How PredictSURE IBD and PROFILE could impact patients such as myself

I’ve experienced a lot during my decade with Crohn’s disease. It has had its moments of being particularly challenging and, at times, hard to cope with. The uncertainty is a response I feel a lot of patients who have lived with this condition for some time will attest to; it does not play fair.

If I could have had my disease course ‘predicted’ with this test, some of the persistent fear, guilt and anxiety would have been resolved. Planning for the future has always been hard when you have the uncertainly of a chronic illness with you. Also, maybe if I had been identified as “high-risk” perhaps earlier treatment with biologics might have resulted in better outcomes, less time in hospital, no surgery. I hope that PROFILE will provide evidence that supports a personalised approach to IBD, and that this makes things better for IBD patients in the future.

Get involved
http://www.crohnsprofiletrial.com/