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


METHODS
Patients with Crohn's disease (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's disease symptoms, inflammatory markers are not persistently normalized, indicating a chronic inflammatory condition that may require continued infliximab therapy.
Department of Medicine, Gastroenterology and Hepatology Unit, Karolinska University Hospital Solna, Sweden.
Maria H
MH
Lönnkvist
Elvar
E
Theodorsson
Mikael
M
Holst
Tryggve
T
Ljung
Per M
PM
Hellström
D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D003424:Crohn Disease / Q000097:blood* / Q000188:drug therapy / Q000473:pathology*; D016232:Endothelins / Q000097:blood*; D005260:Female; D054439:Ghrelin / Q000097:blood*; D006801:Humans; D000069285:Infliximab; D039841:Leukocyte L1 Antigen Complex / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009573:Nitrites / Q000097:blood*; D011237:Predictive Value of Tests; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*; D012720:Severity of Illness Index; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D016232:Endothelins; D054439:Ghrelin; D039841:Leukocyte L1 Antigen Complex; D009573:Nitrites; D055293:Receptors, Urokinase Plasminogen Activator; D002097:C-Reactive Protein; D000069285:Infliximab