2 The diagnostic tests

Clinical need and practice

2.1 Crohn's disease is a chronic condition that causes inflammation of the gastrointestinal tract, particularly the large intestine and the last section of the small intestine. This condition is characterised by recurring periods of active symptoms (flares). At other times health is generally good (remission). According to Crohn's & Colitis UK, 1 in every 650 people in the UK is affected by Crohn's disease. Complications of Crohn's disease include intestinal strictures (narrowing of the affected area of the intestine), fistulas (ulceration of the lining of the gastrointestinal tract) and perforation. Children may also have growth problems because of poor absorption of nutrients.

2.2 The disease course varies a lot from person to person. Some people are at a higher risk of more frequent flares and relapses that do not respond to standard drug treatment. In the long term, they may be at a higher risk of developing complications and may need surgery.

2.3 Crohn's disease has no cure. The goal of treatment is to induce remission by controlling symptoms and maintain remission to prevent relapse. Current standard care is a 'step-up' strategy, which starts with corticosteroids, then immunosuppressants, then biological therapies if the disease does not respond, or loses response, to treatment. NICE's guideline on Crohn's disease covers the management of Crohn's disease in children, young people and adults and recommends the step-up strategy. Step-up treatment involves multiple courses of steroids before changing to a stronger treatment. 'Accelerated step-up' treatment involves rapidly changing to stronger treatments if the expected response is not seen in the time frame. Adequate response can be defined as no clinical symptoms, no signs of ongoing inflammation, or both.

2.4 An alternative approach not currently recommended as standard care is the top-down strategy, which reverses the order of treatment in the step-up strategy, starting with biologics such as tumour necrosis factor (TNF)-alpha inhibitors. It has been suggested that for some people with Crohn's disease, the top-down strategy could achieve a faster and higher rate of mucosal healing. This could potentially modify the natural disease course and allow people with a severe disease course to control it better. Biologics are more clinically effective but are also associated with more side effects.

2.5 Neither the step-up nor the top-down approach are suitable for all people with Crohn's disease. Clinicians in specialist centres may offer the top-down strategy to people if at diagnosis they consider them to have a poor prognosis (for example, if they have significant fistulising disease, complex perianal disease or multiple risk factors). Being able to predict the course of the disease could allow the clinician to identify people who may benefit from the top-down strategy, that is, early treatment with biologics. There is currently no standard means of categorising people based on their risk of having a severe disease course.

2.6 PredictSURE IBD and IBDX tests could identify people at a higher risk of a severe course of Crohn's disease, potentially guiding more personalised disease management.

The interventions


2.7 PredictSURE IBD (PredictImmune) is a whole blood-based biomarker prognostic laboratory-based test combined with a proprietary algorithm to categorise people into a high or low risk of a severe course of Crohn's disease. The test is based on detecting CD8+ T‑cell exhaustion. People with a non-exhausted CD8+ T‑cell signature were linked to a higher risk of frequently relapsing disease. The test involves isolating mRNA from the whole blood sample using the PAXgene Blood RNA kit (QIAGEN), followed by quantitative polymerase chain reaction with reverse transcription (RT‑qPCR) to assess expression of 15 target genes and 2 controls. RT‑qPCR is a 2‑step process: cDNA synthesis in the reverse transcription reaction, and then a qPCR on a 384‑well plate. A maximum of 4 samples may be analysed per plate because cDNA derived from each RNA sample is run in triplicate.


2.8 IBDX (Glycominds) is a panel of 6 indirect solid-phase enzyme-linked immunosorbent assay (ELISA) kits, each of which detects serum levels of specific antiglycan antibodies. Antiglycan antibodies are serological biomarkers thought to be highly specific for Crohn's disease and associated with a severe disease course. The IBDX ELISA kits available to detect specific antibodies include:

  • IBDX anti-chitobioside (ACCA) immunoglobulin A (IgA)

  • IBDX anti-laminaribioside (ALCA) IgG

  • IBDX anti-mannobioside (AMCA) IgG

  • IBDX anti-Saccharomyces cerevisiae (gASCA) IgG

  • IBDX anti-laminarin (anti‑L) IgA

  • IBDX anti-chitin antibody (anti‑C) IgA.

The comparator

2.9 The comparator is standard clinical care in which no test or algorithm is used to predict the disease course. Instead, prognosis is based on clinical judgement of presenting signs and symptoms and known clinical risk factors for a severe disease course.

  • National Institute for Health and Care Excellence (NICE)