Giving Crohn’s drug early ‘cuts need for surgery and further treatment’

Starting people with Crohn’s disease on an advanced therapy soon after diagnosis could dramatically reduce the need for surgery, according to a study.

Prescribing infliximab within two years of diagnosis would be considered “early”, according to University of Cambridge researchers working on the Profile trial, which included 386 newly diagnosed Crohn’s patients from 40 hospitals across the UK.

The study initially set out to test genetic biomarkers in the blood to determine if a person with the condition – which causes parts of the digestive system to become inflamed – was at a higher risk of relapsing.

Researchers found the biomarker test was not likely to help improve outcomes for Crohn’s patients, although a “top-down” approach of prescribing infliximab after diagnosis was “both highly effective and safe”.

According to NHS England, many Crohn’s patients take steroids to manage symptoms and sometimes require immunosuppressants. In some cases, surgery may be required.

The drug infliximab is usually only offered to patients who have regular flare ups and do not respond to other medication.

It works by blocking a protein in the immune system and is administered through intravenous infusions or injections.

Researchers found that prescribing it to patients soon after diagnosis could “prevent the majority of adverse outcomes” from Crohn’s disease.

Professor Miles Parkes, director of the NIHR Cambridge Biomedical Research Centre and chief investigator of the Profile trial, said:  “Up until now, the view has been ‘why would you use a more expensive treatment strategy and potentially over-treat people if there’s a chance they might do fine anyway?’

“As we’ve shown, and as previous studies have demonstrated, there’s actually a pretty high risk that an individual with Crohn’s disease will experience disease flares and complications even in the first year after diagnosis.

“We now know we can prevent the majority of adverse outcomes, including need for urgent surgery, by providing a treatment strategy that is safe and becoming increasingly affordable.”

Researchers split the 386 patients on the Profile trial into two groups.

Half were given conventional treatment while the other half were offered a “top-down” approach and were given infliximab as soon as possible after their diagnosis regardless of symptoms.

The majority (80%) of those on infliximab had their symptoms controlled for one year compared to just 15% in the conventional group.

Some 67% of the infliximab patients also showed no ulcers on an endoscopy at the end of the trial.

About 5% of the patients being treating conventionally required surgery compared to 0.5% in the infliximab group.

Prof Parkes added: “If you take a holistic view of safety, including the need for hospitalisations and urgent surgery, then the safest thing from a patient point of view is to offer ‘top-down’ therapy straight after diagnosis rather than having to wait and use ‘step-up’ treatment.”

First author Dr Nuru Noor, of the Department of Medicine at the University of Cambridge, said the findings – published in The Lancet Gastroenterology and Hepatology – “redefine what should be considered early treatment”.

He added: “Historically, treatment with an advanced therapy like infliximab within two years of diagnosis has been considered ‘early’ and an ‘accelerated step-up’ approach therefore ‘good enough’.

“As soon as a patient is diagnosed with Crohn’s disease, the clock is ticking – and has likely been ticking for some time – in terms of damage happening to the bowel, so there’s a need to start on an advanced therapy such as infliximab as soon as possible.

“We’ve shown that by treating earlier, we can achieve better outcomes for patients than have previously been reported.”

Ruth Wakeman, director of services, advocacy and evidence at Crohn’s & Colitis UK, said: “Crohn’s disease affects over 200,000 people in the UK and we know that many of them have symptoms for a long time before they are diagnosed.

“But diagnosis is not the end of their journey, and the trial and error involved in finding the right treatment can be challenging and distressing.

“This study shows what a dramatic difference early treatment with advanced therapy can make to newly diagnosed patients.

“People with Crohn’s don’t want to be stuck in hospital or having surgery, they want to be out in the world, living their lives. Anything that speeds up the path to remission can only be a good thing.”

The study was funded by Wellcome and PredictImmune Ltd, and supported by the NIHR Cambridge Biomedical Research Centre.