Esophagus to Small Intestine
Clin Gastroenterol Hepatol. 2022;20(9):2059–73.e7
Subclinical persistent inflammation as risk factor for Crohn’s disease progression: Findings from a prospective real-world study of 2 years
Background and aims: Subclinical intestinal inflammation is common in Crohn’s disease. The authors aimed to explore its impact in the disease progression of infliximab (IFX)-treated patients and the usefulness of fecal calprotectin (FC) and C-reactive protein (CRP) as surrogate minimally invasive biomarkers.
Methods: The registry-based, prospective, observational, multicenter DIRECT study (study to investigate the correlation of fecal calprotectin with serum Drug levels and development of an antI-dRug antibodiEs among adult patients with inflammatory bowel disease reCeiving anti-TNF-alpha treatment or vedoluzimab treatment) followed IFX-treated Crohn’s disease patients for 2 years in a tertiary care setting. Persistent inflammation definition was based on FC (> 150 μg/g, > 250 μg/g, or > 350 μg/g) or serum CRP (> 3 μg/ml) concentrations over 2 consecutive or at least 3 visits. Patients were categorized according to a composite outcome reflecting disease progression that incorporated surgery; hospitalizations; new fistulae, abscess, or stricture; and treatment escalation.
Results: Of 322 DIRECT study patients, 180 asymptomatic, IFX treated on maintenance regimen were included in the analysis. Patients developing the composite end point (n = 96) presented higher median levels of FC (205 [interquartile range {IQR}, 98–515] μg/g; p = 0.045) but not of CRP (2.50 [IQR, 0.80–6.00] μg/ml; p = 0.895). Biomarker-defined persistent subclinical inflammation prevalence ranged from 24% to 81%. Considering FC > 250 μg/g in 2 consecutive visits, prevalence was 50%, odds of achieving the end point were increased 3-fold (odds ratio = 2.996, 95% confidence interval: 1.557–5.776), and time-to-outcome occurrence was significantly lower among subjects with persistent inflammation (median time, 11 months). Both clinical-related and treatment-related components were significantly associated with persistent inflammation. Definitions based on CRP > 3 μg/ml, FC > 150 μg/g, FC > 350 μg/g, double biomarkers (FC > 250 μg/g and/or CRP > 3 μg/ml), or more visits did not improve predictive ability.
Conclusions: Persistent inflammation, defined simply and readily by fecal calprotectin > 250 μg/g over 2 consecutive visits, was associated with a significantly higher risk and shorter time to occurrence of a composite outcome reflecting disease progression in asymptomatic infliximab-treated Crohn’s disease patients.