Subclinical Persistent Inflammation as Risk Factor for Crohn's Disease Progression: Findings From a Prospective Real-World Study of 2 Years

• Published in: Clinical gastroenterology and hepatology Vol. 20; no. 9; pp. 2059 - 2073.e7
• Main Authors: Magro, Fernando, Magalhães, Diogo, Patita, Marta, Arroja, Bruno, Lago, Paula, Rosa, Isadora, Tavares de Sousa, Helena, Ministro, Paula, Mocanu, Irinia, Vieira, Ana, Castela, Joana, Moleiro, Joana, Roseira, Joana, Cancela, Eugénia, Sousa, Paula, Portela, Francisco, Correia, Luís, Santiago, Mafalda, Dias, Sandra, Alves, Catarina, Afonso, Joana, Danese, Silvio, Peyrin-Biroulet, Laurent, Dias, Claudia Camila
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2022; WB Saunders
• Subjects: Adult; Anti-TNF-α; Biomarkers; C-Reactive Protein; Crohn Disease; Disease Progression; Fecal Calprotectin; Feces; Humans; Inflammation; Inflammatory Bowel Disease; Infliximab; Leukocyte L1 Antigen Complex; Life Sciences; Prospective Studies; Risk Factors; Tumor Necrosis Factor Inhibitors; CRP; CD; OR; C-Reactive Protein; CI; AZA; HR; IQR; UC; AUC; Fecal Calprotectin; NPV; Anti-TNF-α; PPV; IFX; Inflammatory Bowel Disease; FC; PRO-2
• ISSN: 1542-3565; 1542-7714
• DOI: 10.1016/j.cgh.2021.12.004

Subclinical intestinal inflammation is common in Crohn’s disease (CD). We aimed to explore its impact in the disease progression of infliximab-treated patients and the usefulness of fecal calprotectin (FC) and C-reactive protein (CRP) as surrogate minimally invasive biomarkers.
The registry-based, prospective, observational, multicenter DIRECT (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-alfa treatment or vedoluzimab treatment) study followed infliximab-treated CD 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.
Of 322 DIRECT study patients, 180 asymptomatic, infliximab treated on maintenance regimen were included in the analysis. Patients developing the composite endpoint (n = 96) presented higher median levels of FC (205 [interquartile range, 98–515] μg/g; P = .045) but not of CRP (2.50 [interquartile range, 0.80–6.00] μg/mL; P = .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 endpoint 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.
Persistent inflammation, defined simply and readily by FC >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 CD patients.