Fecal calprotectin is an early predictor of endoscopic response and histologic remission after the start of vedolizumab in inflammatory bowel disease

Abstract

Background and aims: Early prediction of the effect of vedolizumab (VDZ) in inflammatory bowel disease (IBD) is of paramount importance to guide clinical decisions. This study assessed whether early fecal calprotectin (FC) can predict endoscopic response and histologic remission after VDZ initiation. Methods: This was a prospective study. Inclusion criteria were endoscopic inflammation and FC >100 µg/g. FC was determined at baseline and weeks 2, 4, 8 and 16. At week 16, endoscopies with ileal and colonic biopsies were performed. FC changes were assessed with Wilcoxon Rank Sum tests. ROC statistics were used to assess the diagnostic accuracy of FC. Results: In total, 45 patients [27 Crohn’s disease (CD), 16/2 ulcerative colitis (UC)/IBD-unclassified] [40% males, median age 39 (28–51) years] were included. Week 16 endoscopic response and histologic remission rates were 58% and 33%. A median 37% decline in FC at week 2 was observed only in endoscopic responders, p = 0.025. FC <250 µg/g at week 8 predicted endoscopic response in both UC and CD (positive predictive value 100%), whereas absence of FC decline at week 8 corresponded with absence of endoscopic response in CD [negative predictive value (NPV) 82%] and absence of histologic remission in both UC and CD (NPV 90%). Conclusion: The onset of a decline in FC as early as week 2 is associated with endoscopic response to VDZ induction. FC <250 µg/g at week 8 is associated with endoscopic response, whereas absence of FC decline at week 8 is associated with absence of both endoscopic response and histologic remission. FC levels 8 weeks after the start of VDZ could be used to guide clinical decisions and might substitute for endoscopic response evaluation.

Prognostic Value of Fecal Calprotectin to Inform Treat-to-Target Monitoring in Ulcerative Colitis

“…In patients with inflammatory bowel disease treated with vedolizumab, a week 8 FCP concentration of 250 mg/g has been shown to be associated with endoscopic response at week 16 (sensitivity, 65%; specificity, 100%). 19 However, the prognostic value of early changes in FCP concentration for long-term outcomes, as well as an evaluation of the prognostic value of FCP concentration relative to that of other early response measures, has not yet been reported.…”

Inflammatory Bowel Disease Treatments and Predictive Biomarkers of Therapeutic Response

“…Immune markers: Immune markers such as fecal inflammatory markers (calprotectin and lactoferrin) and blood CRP are known predictors of active intestinal inflammation and long-term response to treatment in both CD and UC patients [153,154]. Higher levels of FC displayed an association with non-response to Infliximab in severe UC patients, and were an indication of treatment failure [155,156], whereas a lower level of FC (<250 µg/g), after eight weeks of initiation of Vedolizumab treatment in IBD patients, can positively predict a histological and endoscopic response to therapy [157]. Other emerging fecal inflammatory markers, such as the dimeric M2 isoform of pyruvate kinase (M2-PK), have been found to be more accurate in predicting response to Infliximab in patients with active UC [155] than non-specific FC.…”

Treat‐to‐target and sequencing therapies in Crohn's disease

“…Although prior assessments were 1122 -UNITED EUROPEAN GASTROENTEROLOGY JOURNAL recommended in a timeframe of months, more recent updates and our own practice suggests that most effective therapies can be reassessed using benchmarked targets including fecal calprotectin and bowel wall thickness as assessed by intestinal ultrasound in 6 weeks or even sooner. [19][20][21] In addition to these clear goals, other less considered elements should be examined. The induction of remission should be rapidfrom a patient perspective this would allow time to return to daily activities and reduce disability-related loss of functionality.…”

“…From a practical point of view, timing of disease assessment and target assessment is an evolving priority. Although prior assessments were recommended in a timeframe of months, more recent updates and our own practice suggests that most effective therapies can be reassessed using benchmarked targets including fecal calprotectin and bowel wall thickness as assessed by intestinal ultrasound in 6 weeks or even sooner 19–21 …”