Authors' objectives: The ability to predict whether patients with a new diagnosis of Crohn’s disease will develop disabling disease is an unmet clinical need. Magnetic resonance enterography is a first-line investigation for Crohn’s disease, but its role in prognostication is unknown. To improve prediction of disabling Crohn’s disease within 5 years of diagnosis by developing and internally evaluating a multivariable prediction model comprising clinical predictors and adding magnetic resonance enterography scores (Magnetic resonance Enterography Global Score, Simplified Magnetic Resonance Index of Activity and Lémann Index). To estimate the healthcare costs incurred within 5 years of Crohn’s disease diagnosis and to explore factors driving costs. Crohn’s disease (CD), a subtype of inflammatory bowel disease, is a chronic bowel disorder of uncertain aetiology that is progressive, can affect any part of the gastrointestinal (GI) tract from mouth to anus and typically has a relapsing and remitting disease course. Previously, the treatment of CD involved a stepwise approach guided by symptomatology, with the gradual escalation of drug therapy, including corticosteroids, immunomodulators through biologics, such as anti-tumour necrosis factor agents. However, there is a disconnect between clinical symptoms and the degree of underlying inflammatory activity, so this symptom-directed approach risks severe bowel damage if there is uncontrolled subclinical inflammation. Therefore, there is increasing interest in early treatment with biologic and immunomodulator therapy in a ‘top-down’ fashion to reduce the risk of progressive disease and subsequent complications. Although these agents are highly efficacious for improving symptoms and promoting bowel healing, they are associated with side effects and are relatively expensive, so administering these to all CD patients is inefficient. However, there are no validated or consensus definitions for which patients are most at risk of progressing to disabling CD. A current unmet major clinical need is the ability to accurately identify CD patients at initial diagnosis who are most at risk of developing future disabling CD. This would allow clinicians to administer early, aggressive treatment in those most likely to benefit and avoid unrequired over-treatment in others, so that side effects, complications, costs and clinical outcomes improve overall. A recent systematic review reported five clinical predictors (age, disease duration, disease location, smoking and Montreal behaviour) that demonstrated statistically significant prognostic potential to identify disabling CD. Magnetic resonance enterography (MRE) has become a first-line investigation for CD because it is highly accurate for identifying disease and activity, its extent and distribution, assessing treatment response as well as delineating complications. MRE is well placed to quantify both bowel damage and underlying inflammatory activity concurrently. Given its excellent performance characteristics for staging and monitoring CD, it has been postulated that MRE findings at diagnosis may also be able to predict clinical trajectory, but prognostic research evaluating cross-sectional imaging is lacking. The primary objective was to improve prediction of modified Beaugerie disabling CD (MBDD) within 5 years of diagnosis by developing and internally evaluating a multivariable prediction model comprising clinical predictors and adding predictors based on MRE. Secondary objectives were to improve prediction of disabling disease, defined by Montreal behaviour and Liège criteria, within 5 years of diagnosis, by developing and internally evaluating a multivariable model comprising clinical predictors and adding MRE severity scores. Additional secondary objectives focused on identifying predictive MRE parameters using principal component analysis (PCA) and studying the healthcare costs of CD, specifically to estimate the healthcare costs incurred within 5 years of a new diagnosis of CD and to explore patient, imaging and disease characteristics driving higher health economic costs.

Authors' results and conclusions: We studied 194 patients, median age 29, interquartile range 22–44 years. Within 5 years from diagnosis, 42% (81/194) developed modified Beaugerie disabling disease. There was a univariable association between initial need for steroid therapy and developing modified Beaugerie disabling disease [hazard ratio 2.11 (95% confidence interval 1.36 to 3.26)]. Using risk group definition 1, the baseline clinical model had 49% (95% confidence interval 39 to 60) sensitivity and 66% (95% confidence interval 57 to 74) specificity for predicting the development of modified Beaugerie disabling disease. There was no difference in sensitivity and specificity between models incorporating Magnetic resonance Enterography Global Score, Simplified Magnetic Resonance Index of Activity and Lémann Index compared to the baseline clinical model. Using risk group definition 2, the model, including magnetic resonance enterography predictors, had 86% (95% confidence interval 77 to 92) sensitivity and 35% (95% confidence interval 27 to 45) specificity for predicting the development of modified Beaugerie disabling disease. There was no difference in sensitivity between the clinical model and models incorporating Magnetic resonance Enterography Global Score, Simplified Magnetic Resonance Index of Activity and Lémann Index, but specificity was significantly lower for models incorporating Magnetic resonance Enterography Global Score [29% (95% confidence interval 22 to 38)] and Lémann Index [29% (95% confidence interval 22 to 38)]. The mean total 5-year per-patient cost of health care was £24,267 (standard deviation £33,108). Mean 5-year costs were £29,763 (standard deviation £38,278) compared to £20,327 (standard deviation £28,368) for those with and without disabling disease, respectively. The largest contributor to costs was biologic use. Age under 40 years, presence of perianal disease and presence of severe endoscopic disease were associated with higher costs. Addition of magnetic resonance enterography scores to a multivariable model comprising existing clinical predictors did not improve prediction of modified Beaugerie disabling disease. Healthcare costs were increased in those aged under 40 years and patients with perianal and severe endoscopic disease. We analysed 194 patients. The median age was 29 (interquartile range 22–44) years. Within 5 years of diagnosis, 42% (81/194) of participants developed MBDD. We found evidence of an unadjusted association between initial need for steroid therapy and developing MBDD {hazard ratio 2.11 [95% confidence interval (CI) 1.36 to 3.26]}. Using RD1, the model based on clinical predictors alone (model B) had a sensitivity of 49% (95% CI 39 to 60) and a specificity of 66% (57 to 74) for predicting the development of MBDD. There was no evidence of a significant difference in sensitivity nor specificity between model B and models adding MEGS, sMARIA and LI. Using RD2, model B had a sensitivity of 86% (77 to 92) and specificity of 35% (27 to 45) for predicting the development of MBDD. There was no evidence of a significant difference in sensitivity between model B and models adding MEGS, sMARIA and LI, but specificity was significantly lower for models adding MEGS [29% (22 to 38)] and LI [29% (22 to 38)]. The 6 principal components accounted for approximately 70% of the total variance in a PCA with 20 MRE features. However, we were unable to model the principal components to predict the development of MBDD due to collinearity issues. The mean total 5-year per-patient costs of health care across the whole cohort were £24,267 [standard deviation (SD) £33,108]. For those developing disabling disease (modified Beaugerie criteria), mean 5-year costs were £29,763 (SD £38,278) compared to £20,327 (SD £28,368) for those without disabling disease. The largest contributor to costs was biologic use; a greater proportion of those patients developing disabling disease (modified Beaugerie criteria) received biologics [43/81 (53%)] than those without disabling disease [44/113 (39%)]. According to these unadjusted models, the following factors can be associated with driving higher costs over the first 5 years from diagnosis: age under 40 years at diagnosis, presence of perianal disease at diagnosis and presence of severe (ileocolonic) endoscopic disease at diagnosis. MRE scores at diagnosis were not associated with longer-term costs. In an NHS setting, the addition of MRE activity/bowel damage scores to a multivariable model comprising existing standard clinical predictors did not improve prediction of disabling CD based on a modified Beaugerie criteria definition. Healthcare costs are increased in those aged under 40 years at diagnosis, those with perianal disease at diagnosis and those with severe (ileocolonic) endoscopic disease at diagnosis.

Authors' recommendations: Development and validation of an updated classification system for defining disabling disease. The predictive ability of MRE at diagnosis against alternative definitions for disabling CD. The predictive ability of intestinal US observations for disabling CD.

Authors' methods: A multicentre diagnostic inception cohort. Nine National Health Service hospitals. Aged ≥ 16 years with newly diagnosed Crohn’s disease. Comparative predictive ability of prognostic models, including magnetic resonance enterography scores (Magnetic resonance Enterography Global Score, Simplified Magnetic Resonance Index of Activity and Lémann Index) versus a model based on clinical predictors alone for the development of modified Beaugerie disabling Crohn’s disease within 5 years of diagnosis. Liège and Montreal criteria for disabling disease could not be studied due to an insufficient event rate. Magnetic resonance Enterography or ulTRasound In Crohn’s disease Extended Follow-up (METRIC-EF) for predicting disabling disease was a multicentre, non-randomised, single-arm study of adult patients with newly diagnosed CD. We enrolled patients already recruited to the METRIC trial (ISRCTN03982913) and extended their follow-up for at least 4 years (average follow-up of 5.5 years). Magnetic resonance Enterography or ulTrasound In Crohn’s Disease (METRIC) was a multicentre, prospective trial comparing the diagnostic accuracy of MRE and ultrasound (US) for the location and extent of CD. In METRIC-EF, we drew solely on those patients who were recruited into METRIC with a new diagnosis of CD and extended their follow-up for a minimum of 4 years. To achieve an adequate sample size, we supplemented these patients with a carefully matched, retrospectively identified group of patients, also newly diagnosed with CD and who had undergone MRE within 3 months of diagnosis. MRE was analysed by a pool of GI radiologists with at least 1 year of subspecialty GI imaging experience. Eleven radiologists interpreted MRE examinations from nine recruitment sites, deriving three activity/bowel damage scores: the Magnetic resonance Enterography Global Score (MEGS), Simplified Magnetic Resonance Index of Activity (sMARIA) and the Lémann Index (LI). Consensus panels were convened at each recruitment site. These panels reviewed all available clinical information over the complete follow-up period, including biochemistry, endoscopy, imaging, surgery and overall clinical course. They also recorded the presence or absence of disabling disease. The primary definition of disabling disease was a modified version of that described by Beaugerie et al. We also used alternative definitions, including the Montreal behaviour and Liège criteria. We assumed the prevalence of our MBDD definition of disabling disease would be around 55–60% at 5 years from diagnosis. The sample size was based on, including 207 participants of whom 114–124 we expected to develop MBDD. For the primary objective, we prespecified a multivariable prognostic model for predicting the development of MBDD within 5 years of diagnosis, using clinical predictors measured at diagnosis, unless otherwise stated. The clinical predictors included age, smoking status, sex, disease behaviour (stricturing or penetrating disease), perianal disease, developed MBDD ≤ 90 days from diagnosis, severe endoscopic disease, location of disease behaviour (ileal, colonic, ileocolonic, upper tract), initial need for steroid therapy and weight loss of at least 5 kg prior to diagnosis. We managed missing predictor values via multiple imputation. We evaluated whether adding MRE scores (MEGS, sMARIA and LI) improved the predictive ability of a model based on clinical predictors alone. To evaluate predictive ability, we predefined two risk group definitions (RDs) for classifying patients as high-risk or low-risk for developing MBDD. For RD1, the high-risk patients were the top 40% with the greatest predicted risk. For RD2, the high-risk patients had an absolute risk ≥ 10%. We calculated the absolute risk cut-off by sorting patients by predicted risk and using the risk of the eighth (10% of 81) patient who developed MBDD. For each RD, we estimated and compared the sensitivity, specificity and net benefit of the clinical predictor only model against the models adding MRE severity scores. Due to a lack of patients developing disabling disease according to Montreal behaviour and Liège criteria, we could not fit statistically powered prognostic models. We used PCA to identify the best combination of MRE features for predicting the development of MBDD. We predefined eleven features. We estimated the healthcare costs incurred within 5 years of a new diagnosis of CD and investigated patient, imaging, treatment and other factors driving these costs. We collected NHS hospital resource use data for all patients over the 5-year follow-up period and applied unit costs to these data to calculate average (mean and median) 5-year costs per patient. We used regression analysis to identify the patient, imaging and disease characteristics driving higher NHS costs.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/15/59/17

Year Published: 2026

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/THSN9956

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/THSN9956

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk