Intest Res.  2022 Jan;20(1):101-113. 10.5217/ir.2020.00146.

Biomarker dynamics during infliximab salvage for acute severe ulcerative colitis: C-reactive protein (CRP)-lymphocyte ratio and CRP-albumin ratio are useful in predicting colectomy

• Con D
• Andrew B
• Nicolaides S
• van Langenberg DR
• Vasudevan A

• KMID: 2525077
• DOI: http://doi.org/10.5217/ir.2020.00146

Abstract

Background/Aims
The residual risk of colectomy after infliximab salvage in steroid-refractory acute severe ulcerative colitis (ASUC) is required to inform the need for subsequent maintenance biologic therapy. The aim of this study was to determine the dynamic response of common serum biomarkers to infliximab salvage and assess their utility in predicting subsequent colectomy.
Methods
A retrospective single-center cohort study was conducted on all patients who received infliximab salvage for steroid-refractory ASUC between January 1, 2010, and July 31, 2019. Biomarkers were assessed on admission and days 1 and 3 post infliximab, and included C-reactive protein (CRP)-albumin-ratio (CAR), CRP-lymphocyte-ratio (CLR), platelet-lymphocyte-ratio (PLR) and neutrophil-lymphocyte-ratio (NLR).
Results
Of 94 patients (median age, 35 years; 67% of male), 20% required colectomy at 12 months. Biomarkers on day 3 post-infliximab best differentiated nonresponders, who had higher CRP, lower albumin and lower lymphocyte count (each P< 0.05). Day 3 predictive performance (area under the curve) for 12-month colectomy was best for CAR (0.871) and CLR (0.874), which were similar to Lindgren (0.829; P> 0.05) but superior to Mayo (0.726), partial Mayo (0.719), PLR (0.719), Ho index (0.714), NLR (0.675), Travis score (0.657) and endoscopic Mayo (0.609) (each P< 0.05). A day 3 CAR cutoff of 0.47 mg/g had 79% sensitivity, 80% specificity, 94% negative predictive value (NPV) to predict colectomy; while a day 3 CLR cutoff of 6.0 mg/10⁹ had 84% sensitivity, 84% specificity, 96% NPV.
Conclusions
CAR and CLR measured on day 3 post infliximab salvage for steroid-refractory ASUC represent simple and routinely performed biomarkers that appear to be strong predictors of colectomy. Prospective studies are required to confirm the utility of these predictive scores.

Keyword

Inflammatory bowel disease; Precision medicine; Kinetics

Figure

• 

  Fig. 1. Distribution (median, IQR, range) of biomarkers at baseline, day 1 post infliximab salvage and day 3 post infliximab salvage. (A) CRP; (B) albumin; (C) neutrophil count; (D) CRP on a logarithmic scale; (E) platelet count; (F) lymphocyte count. Values given for patients who avoided colectomy () or proceeded to colectomy () by 12 months. aSignificant differences. IQR, interquartile range; CRP, C-reactive protein.

• 

  Fig. 2. Distribution (median, IQR, range) of predictive scores calculated at baseline (on admission), day 1 post infliximab salvage and day 3 post infliximab salvage. (A) Platelet-lymphocyte ratio; (B) neutrophil-lymphocyte ratio; (C) CRP-albumin ratio; and (D) CRP-lymphocyte ratio. Values are given for patients who avoided colectomy () or proceeded to colectomy () by 12 months. Each graph is displayed using a logarithmic Y-axis. aSignificant differences. IQR, interquartile range; CRP, C-reactive protein.

• 

  Fig. 3. Kaplan-Meier estimates for colectomy-free survival for patients who received salvage infliximab for steroid-refractory acute severe ulcerative colitis. Kaplan-Meier curves according to risk group stratified by: (A) day 3 CAR at 0.47 mg/g; (B) day 3 CLR at 6.0 mg/109. CRP, C-reactive protein; CAR, CRP-albumin ratio; CLR, CRP-lymphocyte ratio.

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