An Addenbrooke’s-led study is the first to provide clear evidence that using more powerful treatments earlier has long-term benefits for people living with Crohn’s disease. These findings have been widely welcomed by patients and world-leading experts.
Under existing guidance, people with Crohn's disease typically start advanced treatment only once they have more severe symptoms and disease complications. However, evidence from the trial instead supports an approach known as ‘top-down’ treatment where patients start on advanced biologic medications such as infliximab or adalimumab, as soon as possible after diagnosis.
Published today (11 September 2026) in The Lancet Gastroenterology & Hepatology, over 350 patients were followed for an average of five years after diagnosis. Those in the top-down group were 2-times less likely to progress to more complicated disease, 2-times less likely to be admitted to hospital, and had 5-times lower risk of needing abdominal surgery.
Chris Dromgoole took part in the trial after being diagnosed with Crohn’s disease in late 2021. The 33-year-old from Newmarket said:
I feel incredibly lucky to have been on the trial. My symptoms improved almost as soon as the treatment started, I haven’t spent any time in hospital and I’ve had next to no problems. You hear a lot of stories about the complications of Crohn’s disease and I hope the results of the trial will help more people to avoid them.
Crohn’s disease is a form of inflammatory bowel disease (IBD). It is a life-long condition that affects around one in 350 people in the UK, with around 10,000 diagnosed each year. It can significantly impact quality of life with symptoms such as stomach pains, diarrhoea or constipation, weight loss and fatigue.
If you have IBD and interested in research, consider taking part in the IBD BioResource.
The PROFILE trial shows what a dramatic difference early treatment with advanced therapy can make to people who have just been diagnosed with Crohn’s disease. Being told you have a lifelong condition is a lot to take on board and it is vital that patients are involved in decisions about their care. No one knows the daily reality of Crohn's or colitis better than the person living with it. Having access to safe, effective drugs is a real positive so that patients everywhere can benefit from these research findings.
Marianne Radcliffe, CEO of Crohn's & Colitis UK
These findings really are a game changer for those of us working to support and improve the lives of people living with this condition. This is the first study to robustly show that effective treatment from the point of diagnosis can slow long-term progression of Crohn’s disease.
Professor Nick Powell, Chair of the British Society of Gastroenterology (BSG) IBD Clinical Research Group
Current treatment for Crohn’s disease focuses on managing symptoms, which go through phases of being more or less severe. However, overall damage to the bowel generally progresses and worsen over time.
The new findings are the latest results from PROFILE, a trial supported by the National Institute of Health and Care Research (NIHR), which ran from 2017 to 2022. It compared outcomes between patients on the standard treatment approach, known as ‘step-up’, against those on the top-down approach. Patients have now been followed for an average of 5 years since joining the trial.
These long-term findings from PROFILE help to answer one of the most important questions that people have been asking for decades. Is it possible to modify the course or alter the natural history of Crohn's disease? Our data provide perhaps the most compelling evidence to date, that this can be achieved, by offering early effective therapy to patients – as soon as possible after diagnosis.
Dr Nurulamin Noor, Clinical Lecturer in Gastroenterology and first author for the PROFILE trial
Last year Dr Noor was named Young Gastroenterologist of the Year by the BSG and was awarded an NIHR Impact prize for his work on the PROFILE trial.
The new results from the over 350 patients included in the follow-up show that over the 5-year period:
- 26 patients on step-up treatment needed surgery vs. 6 on top-down.
- Disease progressed in 17% of step-up patients vs. 7% of top-down
- 34% of step-up patients were admitted to hospital vs. 24% of top-down
This is the first study to convincingly show that we can modify the course of Crohn’s disease. These new 5-year findings from the PROFILE trial will have a major international impact, and support global efforts to reduce time-to-diagnosis, time-to-treatment, and start the appropriate treatment strategy. Implementing these findings into clinical care should help improve outcomes for patients living with Crohn’s disease all around the world.
Professor Fernando Magro, President of the European Crohn’s and Colitis Organisation (ECCO)
While the step-up approach escalates treatment as a patient’s symptoms or inflammation worsen, the top-down approach start patients on biologic therapies – which directly target inflammation – as soon as possible after diagnosis.
PROFILE is already referenced worldwide in guidance on treating Crohn’s disease. It has shown short-term benefits for patients in the first year (opens in a new tab) after diagnosis and an economic analysis found top-down therapy could save the NHS £20 million per year by reducing symptom flares, hospital admissions and surgical procedures.
Infliximab and adalimumab are existing drugs already used to treat a range of autoimmune diseases. The top-down approach just changes the timing of when these treatments are used in Crohn’s disease.
The PROFILE trial was led by Professor Miles Parkes, Consultant Gastroenterologist at Addenbrooke’s Hospital and Director of the NIHR Biomedical Research Centre (BRC): Cambridge.
The findings are striking. The data from PROFILE now clearly show that early “top-down” anti-TNF therapy from diagnosis is more effective and safer over both the short and long term, and saves money for the NHS and healthcare systems. These findings will change treatment for people newly diagnosed with Crohn’s disease around the world.
Professor Miles Parkes
This work is an outstanding example of the clinical and academic community coming together to address a key unmet need. This type of work is not typically undertaken by commercial organisations and highlights the vital role of the clinical academic community in advancing patient care.
Professor Duncan Richards, Head of Department of Medicine at the University of Cambridge School of Clinical Medicine
PROFILE originally recruited almost 400 patients from across 40 hospitals in the UK. It was sponsored by CUH and the University of Cambridge and was supported by Crohn’s and Colitis UK, Wellcome, Celltrion, the NIHR BRC: Cambridge, NIHR Research Delivery Network and Cambridge Clinical Trials Unit.
The NIHR is proud to continue to support PROFILE into its second phase. This important study continues to have a hugely positive impact on newly diagnosed people with Crohn’s disease both in the UK, and around the world.
Professor Lucy Chappell, Chief Scientific Adviser at the Department of Health and Social Care and Chief Executive Officer of NIHR
Chris’s story
Chris first started feeling unwell during a trip to Venice in Spring 2021. After a period of flu-like symptoms he started getting stomach pains and increasingly severe symptoms, sometimes needing the toilet more than 12 times a day.
Chris was referred to Addenbrooke’s Hospital where he was diagnosed with Crohn’s disease and invited to join the PROFILE trial.
Joining this trial felt like an easy decision. The treatments were all well understood, it was just about a difference in timing. I figured there wasn’t really anything to lose and there was a chance to make things better for myself and other people.
Chris, PROFILE trial participant
During the trial, Chris visited hospital for a few hours every two months to receive infusions of infliximab as well as a regular tablet medication called azathioprine.
Right away, everything was 95% better, I was quickly back to a normal life and didn’t need to worry about my health. It was a huge relief. In the last five years I’ve had one small relapse for a few weeks but recovered quickly.
Chris enjoys getting out in the countryside and says being on treatment has given him back that freedom. He is also in the process of renovating his home and will be getting married later this year to, Natalia, his partner for the last 10 years.
Chris has continued on the same treatments since the trial but is now able to get them as an injection that he gives himself at home every two weeks.
I’m hugely grateful to everyone at Addenbrooke’s. I say to everyone how amazing it is to live in a part of the world where I have free access to specialist healthcare, cutting-edge clinical trials, and I can just get these powerful, effective treatments delivered right to my door.