Blood chemistry markers for evaluation of inflammatory activity in Crohn's disease during infliximab therapy

Abstract

Objective. There is a discrepancy between clinical activity and biomarkers in inflammatory bowel disease. The Harvey–Bradshaw index (HBi) is steadfast to evaluate disease activity. A set of biological markers (high sensitive C-reactive protein [hs-CRP], calprotectin, total nitrite, soluble urokinase Plasminogen Activator Receptor [suPAR], ghrelin and endothelin) are investigated to study inflammatory activity and correlation with HBi during infliximab therapy. Material and methods. Patients with Crohn'sdisease (n = 22) were assessed and blood samples drawn before and 1 week after infliximab infusion (5 mg/kg) and repeated after 6 months, and compared to healthy volunteers. Hs-CRP, calprotectin, suPAR, ghrelin and endothelin were analyzed with immunoassays, and total nitrite with Griess-reaction. Results were analyzed with Wilcoxon matched-pairs test, Mann–Whitney test and Spearman correlations. Results. After the first infusion visit, HBi and calprotectin values decreased while nitrite increased (p < 0.05). At the 6-month visit, pre-infusion index and biomarkers had returned to baseline levels. Post-infusion, again the values of HBi, hs-CRP and calprotectin decreased (p < 0.05). The suPAR levels did not change between pre- and post-infusion periods at either visit. Calprotectin, nitrite and suPAR differed from healthy controls throughout the study (p < 0.05). Endothelin decreased with each treatment but was, like ghrelin, not different from controls. We found HBi to correlate with hs-CRP (Spearman r = 0.32, p < 0.05), but calprotectin did not, neither did nitrate nor suPAR. Conclusions. Although infliximab ameliorates Crohn'sdisease symptoms, inflammatory markers are not persistently normalized, indicating a chronic inflammatory condition that may require continued infliximab therapy.

Key Words::

• Biological treatment
• biomarkers
• Harvey–Bradshaw index
• inflammatory bowel disease

Acknowledgements

The study was supported by the Swedish Research Council (7916), Karolinska Institutet and Uppsala University.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.