Fecal Calprotectin Responses Following Induction Therapy With Vedolizumab in Moderate to Severe Ulcerative Colitis: A Post Hoc Analysis of GEMINI 1

Abstract

BackgroundIn patients with ulcerative colitis (UC), fecal calprotectin (FC) concentrations correlate with endoscopic inflammation evidence. This study investigated the effect of vedolizumab induction on FC concentrations and whether FC concentrations could be a reliable surrogate measure of disease status.MethodsData from the placebo-controlled, phase 3 trial GEMINI 1 were used to evaluate week-6 relationships between outcomes (including clinical remission, mucosal healing [MH], and endoscopic remission) and both absolute FC concentration values and relative FC concentration changes from baseline (%FC0-6). Sensitivity and specificity were calculated by cross-tabulation; the value of week-6 FC concentration as surrogate biomarker was measured with Youden J statistic computed for various cut points.ResultsGEMINI 1 induction phase enrolled 895 patients. Fecal calprotectin concentration decreases were deeper in patients with clinical remission, MH, and/or endoscopic remission than in patients without. The best week-6 indicator of clinical or endoscopic remission in this data set was absolute FC concentration ≤150 µg/g. The surrogate biomarker values (based on areas under the curve) for the best-performing cut points (FC0-6 reduction >90%, FC ≤150 µg/g) were fair (range, 0.70–0.77, total population). More patients met the ≤150 µg/g cut point with vedolizumab than with placebo. Baseline FC concentrations were not correlated with clinical outcomes.ConclusionsFecal calprotectin concentration reductions were greater with vedolizumab induction than with placebo. Week-6 FC concentrations had only fair surrogate biomarker value for endoscopic status. Our data suggest that, while FC may reflect inflammatory burden, FC concentration after vedolizumab induction may not be a robust biomarker of mucosal inflammation.

Fecal calprotectin is a reliable marker of endoscopic response to vedolizumab therapy: A simple algorithm for clinical practice

“…In previous studies, analyzing data from the GEMINI UC registration trial on the ability of FC in combination with clinical data on week 6 to predict endoscopic remission have shown only moderate predictive value 21,22 . A possible explanation for the discrepancy between these findings and the accurate correlation of FC and endoscopy in our study may be that in the VDZ registration trials the evaluation of the response to VDZ induction have been scheduled too early.…”

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

“… 28 FC data from the GEMINI I trial have shown only a moderate predictive value of FC at week 6 to predict endoscopic remission at week 6. 19 Possible explanations for the discrepancy between these findings and the high diagnostic accuracy of low FC and endoscopic response in our study are not only the earlier timing of the endoscopy in the GEMINI trial but, most importantly, the endpoint of endoscopic remission instead of endoscopic response. Taken together, the GEMINI and our study suggest that a response to VDZ with improvement of mucosal inflammation may be evaluated as early as week 8, whereas the optimal timing to evaluate further improvement towards mucosal healing requires further research.…”

“… 12 , 14 – 18 To date, the potential of FC to early predict response to VDZ induction therapy is largely unknown as studies have mainly focused on a single FC measurement. 19 To investigate whether early FC level measurements are indicative for mucosal improvement, as observed by endoscopy and histology at week 16, FC levels at predefined time points were assessed after the initiation of VDZ therapy.…”

Assessment of serum cytokines predicts clinical and endoscopic outcomes to vedolizumab in ulcerative colitis patients

“…39 It has been proposed as a predictive marker of mucosal healing in UC patients treated with anti-TNF, 40 and of clinical remission in patients treated with VDZ. 19 Of note, both clinical trials 41 and real life studies 18 highlighted that VDZ promoted a significant reduction of FC in UC patients. However, the evaluation of FC, as a predictive marker of mucosal healing in VDZ-treated patients, has never been investigated.…”