Inflammatory Biomarkers and Clinical Remission in Patients with Active Crohnʼs Disease: Results from PRECiSE 2

Abstract

Purpose: Low baseline (BL) C-reactive protein (CRP) concentrations (<10 mg/L) are associated with high placebo response rates (47%-60%) in patients (pts) with active Crohn's disease (CD)1,2 and greater treatment effects with anti-TNF agents vs placebo have been reported in pts with higher BL CRP concentrations.1 PRECiSE 2 (P2)3 has demonstrated efficacy for the anti-TNF certolizumab pegol (CZP) in pts with active CD. This post hoc analysis of P2 data aimed to determine the value of biomarkers in predicting longer term remission. Methods: In P2 (NCT00152425), pts who responded to CZP induction (n=428) were randomized to continuous therapy with CZP or placebo during Wks 6-26. BL CRP and fecal calprotectin (FC) concentrations were determined at Wk 0 and the Wk 26 remission rates were stratified according to CRP and FC cut-offs and analyzed for the difference between CZP and placebo remission rates (remission delta). Results: The highest remission deltas were achieved in pts on continuous CZP with high BL CRP or FC vs patients on placebo (Table). High levels of both CRP and FC at BL corresponded with lower absolute remission rates for both placebo and CZP group but still with preservation of a numerically high remission delta. In pts with no elevation in either CRP or FC, the Wk 26 remission rate was the highest observed among all of the placebo groups. CZP plasma concentrations were generally higher in patients with low levels of both CRP and FC and in patients with high FC but low CRP and conversely, were generally lower in patients with high levels of both CRP and FC and in patients with high CRP but low FC.TableConclusion: In CD pts receiving CZP, high levels of both CRP and FC coincide with lower remission rates; conversely, low levels of CRP and FC coincide with high levels of remission in both CZP- and placebo-treated patients. High CRP, with or without high FC, may be associated with lower CZP plasma concentrations. These data suggest that either high CRP or high FC levels at BL may be useful in predicting long-term remission and indicate that further work on understanding normalization of biomarkers in CD by adjusting anti-TNF therapy is warranted.