P504 The variation of faecal calprotectin after 3 months of anti-TNF therapy is a predictor of sustained clinical remission in patients with Crohn's disease

Abstract

Background: Mucosal healing is recognised hitherto as the best therapeutic endpoint in patients with Crohn's disease (CD) but its use in daily practice is limited by the low acceptability of repeated colonoscopies. In this context, faecal biomarkers are attractive alternatives. Faecal calprotectin (Fcal) is a reliable marker of endoscopic mucosal activity. However, its sensitivity to change under treatment remains poorly evaluated.1,2 In the present study, we aimed to assess if the level of Fcal after 12 weeks of anti-TNF therapy was predictive of steroids-free clinical remission (CFREM) at 1 year. Methods: CD adult patients needing anti-TNF therapy with CDAI >150 and elevated Fcal (>100 μg/g) were consecutively enrolled in this prospective study. Fcal measurement (immunochromatographic assay) was performed before staring medication (Week 0) and at 12 weeks (Week 12). Patients were treated with adalimumab or infliximab in monotherapy or combination therapy with immunosuppressive drugs. Therapeutic intensification was performed from Week 12 only in cases of clinical relapse (CDAI > 150 requiring therapeutic intensification, hospitalisation or surgery). CFREM was defined as CDAI <150 and CRP < 5 g/l with no switch of anti-TNF agents and no bowel resection. Results: Overall 40 CD patients were included (Table 1). The median Fcal level at Week 12 was significantly lower (646.0 μg/g [315.0-1567.0] vs. 100.0 μg/g [100.0-193.0], p < 0.001) and the relative decrease of Fcal between Weeks 0 and 12 was higher (83.3 % [33.6-83.3%] vs. 0.0 % [0.0-33.2 %], p = 0.001) in the patients in CFREM compared with those who were not. Using ROC curve (AUC = 0.85), we determined that an Fcal < 300 μg/g was the best threshold for predicting CFREM at 1 year (Se = 84.6%, Spe = 77.8%, PPV = 64.7%, NPV = 91.3%, accuracy = 80.0%). A 50% decrease of Fcal was also predictive of CFREM at 1 year (AUC = 0.82, Se = 61.5%, Spe = 88.9%, PPV = 72.7%, NPV = 82.8%, accuracy = 80.0%). We studied the complementarity of these two thresholds by creating a composite criterion called biological response (Fcal < 300 μg/g at Week 12; or, for patients with initial Fcal < 300 μg/g, at least 50% decrease or normalisation of Fcal (< 100 μg/g)). Biological response predicted CFREM at 1 year with the following performances: Se = 76.9%, Spe = 92.6%, PPV = 83.3%, NPV = 89.3%, accuracy = 87.5%. Furthermore, Fcal < 300 μg/g or a biological response at Week 12 were protective factors of therapeutic intensification for clinical relapse: Hazard ratio (HR) = 0.15[0.03-0.67] (p = 0.013) and HR = 0.11[0.01-0.85] (p = 0.035), respectively. Conclusions: Fcal is a reliable biomarker to assess therapeutic efficacy in patients with CD treated with anti-TNF therapy. Fcal should be considered as a therapeutic target in patients with CD.