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

Maria H. Lönnkvista, Elvar Theodorssonb, Mikael Holstc, Tryggve Ljungd & Per M. Hellström*ea Department of Medicine, Gastroenterology and Hepatology Unit, Karolinska University Hospital Solna, Swedenb Department of Clinical and Experimental Medicine/Clinical Chemistry, Linköping University, Linköping, Swedenc Department of Woman and Child Health, Karolinska University Hospital Solna, Swedend Merck, Sharp & Dohme, Stockholm, Swedene Department of Medical Sciences, Uppsala University Hospital, Uppsala, SwedenCorrespondence: Per M. Hellström, MD, PhD, Department of Medical Sciences, Uppsala University Hospital, Bldg 40, SE-751 85 Uppsala, Sweden. +46 18 611 4285. +46 18 510 133. Per.Hellstrom@medsci.uu.se 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.