Fecal calprotectin concentration and clinical response to certolizumab pegol inpatients with active Crohn's disease: results from PRECiSE 2

Purpose: Greater treatment effects with anti‐TNF agents have been reportedin patients with higher baseline inflammatory marker concentrations.1 Fecal calprotectin(FC), a neutrophil‐derived protein, can be used as a marker of intestinalinflammation.2 The aim of this post hoc analysis of PRECiSE 2 data3 was to determinethe relationship between concentrations of FC and clinical outcome inpatients with active Crohn's disease. Methods: In PRECiSE 2 (NCT00152425), adult patients (N=668) with activeCrohn's disease. (Crohn's disease. Activity Index [CDAI] 220‐450) received open‐labelinduction with certolizumab pegol 400 mg at Weeks 0, 2, and 4. Patients (n=428)responding to induction therapy at Week 6 were randomized to continuous therapywith certolizumab pegol 400 mg or placebo every 4 weeks during Weeks 6‐26. Week 6 response rates (CDAI score reduction >100 from baseline) and Week 6and Week 26 remission rates (CDAI score <150) were determined in subgroups ofpatients stratified by baseline and Week 6 FC concentrations. Results: The overall geometric mean (gm) baseline FC concentration was veryhigh (359 lg/g). The gmFC concentrations at baseline and Week 6 were loweramong Week 6 responders vs nonresponders, but failed to reach significance. ThegmFC concentrations at Week 6 were lower vs baseline values (p=0.0143) amongWeek 6 responders, but not among Week 6 nonresponders (p=0.5198). Amongremitters at both Week 6 and Week 26, gmFC concentrations at baseline and Week6 were lower in the placebo vs certolizumab pegol group, but failed to reach significance.The gmFC concentrations at baseline and Week 6 were significantlylower in patients in remission at Weeks 6 and 26 vs gmFC concentrations at baselineand Week 6 in Week 6 nonremitters. Conclusion: High baseline FC concentration suggests that patients in PRECiSE 2carried a high inflammatory burden. Lower FC concentration among remitters in theplacebo vs certolizumab pegol group is consistent with high placebo response ratesamong patients with low inflammatory biomarker concentrations and active Crohn'sdisease. Improved FC concentration from baseline to Week 6 among Week 6 respondersis consistent with effective Crohn's disease therapy positively influencinginflammatory biomarker levels. Correlating inflammatory biomarkers and response totreatment may enhance the understanding of how biomarkers can guide therapy.