P415 Fecal calprotectin and serum C-reactive protein predict outcome of infliximab induction therapy in inflammatory bowel disease.
P.M. Hellström*1, H. Diaz1, M. Lonnkvist1, R. Befrits2
1Uppsala University, Department of Medical Sciences, Uppsala, Sweden, 2Karolinska Institutet, Department of medicine, Stockholm, Sweden
The neutrophil granulocyte-derived protein calprotectin is an inflammatory marker in Crohn's disease (CD) and ulcerative colitis (UC). We assessed the importance of the numerical decrease of FC with infliximab induction therapy with C-reactive protein (CRP) and clinical activity evaluated by Harvey-Bradshaw index (HBi) and partial Mayo score (pMS).
Out of 180 patients with IBD, 144 with CD and 36 with UC were treated with infliximab. Indices, FC and CRP were evaluated at two occasions: at baseline before infliximab introduction and after 12 weeks. Responders were followed 24 weeks further to assess the FC values with incident outcome. Values are presented as median and interquartile range (IQR). Spearman nonparametric correlation test served for correlation analyses. Sensitivity, specificity and likelihood ratio were analyzed using the ROC (receiver operating characteristic) curve. Survival curves were analyzed with Kaplan-Meier analysis and log-rank test. P<0.05 was considered significant.
After induction, 151 patients (83%) responded to therapy and 116 (65%) attained clinical remission. At baseline, HBi was 11 (6.5-17.5), pMS 8.5 (7.5-9), FC 2060 (1495-5507) µg/g and CRP 13 (6.5-35.5) mg/L. Following induction therapy, indices, FC and CRP declined from baseline levels (all p<0.01). Among responders, FC decreased to 210 (70-358) µg/g compared with non-responders 1425 (304-2171) µg/g. The corresponding CRP levels were 2 (1-4) mg/L and 5.5 (3.5-27.5) mg/L. In those reaching remission, FC and CRP decreased to 207 (75-354) µg/g and 2 (1-3.5) mg/L, respectively. Clinical responders were followed 24 weeks to predict incidents (dosage increase, shortening of infusion interval, surgery) based on FC levels. The ROC optimal cut-off point was 221 µg/g (sens 90%, spec 71%, likelihood ratio 3.15). Area under the curve was 0.88. Using FC 221 µg/g as cut-off, FC exceeding 221 µg/g after induction therapy was studied in conjunction with an incident within 24 weeks. In those with FC < 221 µg/g, two out of 75 patients (3%) had an incident within 24 weeks of induction therapy, among those with FC >221 µg/g that number was 25 out of 41 (61%) within the same period. Clinical activity correlated with FC (Spearman r=0.62, p<0.001) as well as with CRP (Spearman r=0.60, p<0.001).
Clinical indices (HBi, pMS) correlate well with FC and CRP levels during infliximab induction therapy. The indices, FC and CRP levels decreased significantly from baseline levels among patients responding to infliximab treatment. However, a FC level >221 µg/g after induction therapy is associated with a disease incident within the following 24 weeks in half of the cohort.