July 14, 2025
What is the diagnostic accuracy of noninvasive biomarkers and imaging for evaluating postoperative recurrence in Crohn’s Disease compared to colonoscopy?
Non-invasive tests offer reasonable alternatives to colonoscopy when assessing post-operative recurrence in Crohn’s disease. Many patients with normal findings on individual tests (or panels of tests) could avoid colonoscopy.
Samnani S, Ray CM, Gill P, et al. Diagnostic Accuracy of Noninvasive Biomarkers and Imaging for Evaluating Postoperative Recurrence in Crohn’s Disease. Clin Gastroenterol Hepatol. Epub ahead of print June 2, 2025. https://www.cghjournal.org/article/S1542
This systematic review and meta-analysis compared the diagnostic accuracy of noninvasive methods for detecting Crohn’s disease (CD) recurrence after surgical resection to colonoscopy, which is the gold standard.
The analysis included 17 studies of 1,080 patients that evaluated inflammatory biomarkers and 20 studies of 1,053 patients that assessed imaging measures. Most studies (14/17 evaluating biomarkers and 16/20 evaluating imaging) were prospective and deemed to be at low risk for bias. The authors defined endoscopic recurrence as a Rutgeerts’ score ≥i2 (or ≥i2b in studies using the modified score).
Five studies described the diagnostic accuracy of C-reactive protein (CRP) at multiple thresholds. At a 5 mg/L threshold, CRP demonstrated pooled sensitivity of 0.45 (95% confidence interval [CI], 0.33–0.58) and specificity of 0.83 (95% CI, 0.68–0.92). There was no significant heterogeneity among CRP studies (I²=0%). The CRP threshold used significantly impacted performance, with increasing thresholds decreasing sensitivity but increasing specificity and the relative diagnostic odds ratio.
Fifteen studies evaluated fecal calprotectin (FC), with thresholds ranging from 50 μg/g to 274 μg/g. At 50 μg/g, FC showed a pooled sensitivity of 0.76 (95% CI, 0.70–0.82) and specificity of 0.66 (95% CI, 0.56–0.75). There was moderate heterogeneity for FC studies (I²=43%). Analysis showed that for every 10 μg/g increase in FC threshold, the positive likelihood ratio of a CD diagnosis increased by 2.25 (95% CI, 1.71–2.97) while the negative likelihood ratio increased by 0.30 (95% CI, 0.19–0.46), indicating improved specificity with moderate reductions in sensitivity.
Seven studies evaluated computed tomography enterography (CTE) and/or magnetic resonance enterography (MRE), using 11 different definitions of imaging-based recurrence. The pooled sensitivity and specificity for CTE or MRE analyzed together was 0.89 (95% CI, 0.73–0.96) and 0.65 (95% CI, 0.43–0.82), respectively. In sensitivity analysis using MRE alone, the sensitivity was 0.92 (95% CI, 0.35–1.00) and specificity was 0.73 (95% CI, 0.49–0.89). Heterogeneity dropped from 54% for combined CTE/MRE to 31% for only studies that looked at MRE.
Thirteen studies evaluated intestinal ultrasound (IUS) using 29 different definitions of sonographic recurrence. The most commonly used parameters were bowel wall thickness >3 to 5 mm at the neoterminal ileum, color Doppler flow, inflammatory fat and complications such as stenosis, fistula or abscess. Despite varying definitions, there was no significant heterogeneity (I²=26%).
The pooled sensitivity for IUS was 0.89 (95% CI, 0.75–0.96) and the specificity was 0.76 (95% CI, 0.52–0.90). Performance was improved in sensitivity analysis using optimized radiographic parameters: oral contrast enhancement, increasing the bowel wall thickness threshold from 3 mm to 5 mm, or combining multiple sonographic parameters (abnormal contrast enhancement, Doppler flow or mesenteric lymph nodes). With the optimized definitions, the sensitivity of this modality improved to 0.93 (95% CI, 0.80–0.98) and specificity rose to 0.85 (95% CI, 0.71–0.93).
The study has notable limitations, the authors noted. These include heterogeneity in study designs and populations, reliance on Rutgeerts’ score (which has known inter-rater variability), variable follow-up durations across studies and inability to evaluate prevalence-specific diagnostic accuracy estimates. Additionally, because few studies evaluated symptomatic patients, the findings are largely generalizable only to asymptomatic patients. The analysis was also limited by differing radiographic definitions of recurrence between studies.
Details
Study Design: Systematic review and meta-analysis
Funding: Not stated
Allocation: Not applicable
Setting: international
Level of Evidence: 1a