Figure 2: a) in the absence of a reliable prognostic test, it is not possible to distinguish between patients likely to follow a quiescent disease path and those likely to follow a more aggressive, relapsing-remitting course, so all patients are treated the same. b) the PredictSURE IBD test enables patients to be stratified based on risk of following an aggressive disease course, with those at high-risk likely to benefit from top-down therapy and close monitoring. Low-risk patients are likely to benefit from a less aggressive step-up approach.
The ability of PredictSURE IBD to reliably classify patients into high- or low-risk of following a frequently relapsing disease course has been previously demonstrated during development and validation clinical studies. Further validation studies are planned or ongoing in different cohorts around the world, including the PRECIOUS trial which is recruiting across the USA. PROFILE is the first randomised clinical trial of this biomarker, and is assessing whether use of this blood test to guide initial treatment strategy will result in better clinical outcomes for patients. The economic impact of this biomarker-stratified approach will also be assessed as part of the PROFILE trial analyses.
The study started recruiting in December 2017 and has been delivered by a multidisciplinary team led by the Chief Investigator Professor Miles Parkes and Clinical Research Fellow Dr Nuru Noor. The trial is managed by the Cambridge Clinical Trials Unit and is co-sponsored by Cambridge University Hospitals NHS Foundation Trust and University of Cambridge. PROFILE is overseen by an international team of independent experts in IBD, clinical trials, and statistics.
Prior to the COVID pandemic, PROFILE had opened to recruitment at 40 sites around the UK with recruitment reaching 15 patients per month by the end of 2019 and a total 215 participants recruited. With 14 months to go, the target of 400 patients was looking very achievable. Then the world changed with the spread of the COVID-19 pandemic.
The effects of the pandemic were felt immediately, as hospitals switched focus to COVID-19 clinical care and COVID-19 research projects only. Recruitment to the PROFILE trial dropped dramatically in the first quarter of 2020 before stopping completely in April 2020.
The PROFILE trial team felt it was important to keep the trial open for patients and implemented several modifications to make the trial protocol more patient-centred and allow increased flexibility of data collection for both researchers and patients. These modifications included the possibility for home delivery of medications, virtual data collection, greater use of non-invasive or point of care investigations, and the option for remote monitoring visits.
This was a decision welcomed by many sites and patients around the country. Sites were able to open to recruitment later in the summer of 2020 with the number of sites able to recruit increasing as the year progressed. PROFILE was highlighted by the National Institute for Health Research as a national exemplar trial on how to make modifications and continue successful delivery as part of a national research recovery programme in the post-pandemic period. PROFILE was also designated as a national priority non-COVID research studies around the UK, due to its impact on patients living with CD both in the UK and around the world.
As a consequence of the pandemic and rising recruitment rates in the latter half of 2020, the trial team and funders supported the decision to continue recruiting new participants until the end of 2021. The trial closed for recruitment in December 2021 with a total of 369 patients enrolled. PROFILE is the largest academic interventional IBD trial ever conducted in the UK and one of the largest academic IBD trials ever conducted worldwide. The trial follows all participants for 12 months, ending with a final trial visit and end of trial procedures. This follow-up period should complete in December 2022, with several months of data cleaning, central reading and statistical analysis required before results can be reported.
The whole team is excited about seeing the final results and sharing them with IBD clinicians and patients alike. We expect the results to be presented and submitted for publication during 2023. We are excited about the impact these results may have on clinical management in CD, anticipating that there will be demonstrable clinical benefit by using a prognostic risk stratified approach to guide treatment of CD patients. Such an outcome could lead to the PredictSURE IBD test being adopted as a routine tool to help guide treatment decisions and make personalised medicine a reality for patients living with IBD.
Successfully completing recruitment to the PROFILE trial, despite the challenges encountered over the last two years, is a real achievement and a testament to the hard work and determination of everyone involved in trial. We would like to thank the central trial team and leadership, collaborators, patients and public involvement representatives, company stakeholders, and especially to all the participants who enrolled in the trial itself for making it such a huge success.