Sa1235 PKM2 As a Novel Serum Biomarker of IBD Activity, A Early Pilot Study

Abstract

Introduction: In the last two decades the therapeutic paradigm of Crohn's disease (CD) has changed dramatically thanks to the use of biological drugs. In this scenario, we must consider the pivotal role of tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine, in the pathogenesis and relapse of CD. High levels of TNF-α have been associated with the development of intestinal inflammation in CD and blocking this cytokine with anti-TNF-α molecules may result in mucosal healing. In addition several studies have shown increased TNF-α levels in the serum and in the intestinal mucosa of patients with CD. However, little is known about the course of TNF-α levels and their relationship with disease recurrence in CD patients during maintenance treatment with Adalimumab. Aim: We assessed TNF-α levels in patients with CD who were in maintenance treatment with ADA and correlated them with clinical and endoscopic disease activity. Methods: In this prospective observational cohort study, performed at a single tertiary referral center, 23 [14M/9F; mean age 41 (range 21-66) infliximab-Naive patients with CD in maintenance treatment with ADA were included and followed-up. Blood samples were drawn at standardized time points (i.e. at 6, 12, 18, 24 months and in case of CD relapse) just before ADA injection. Antibodies against ADA (AAA) were measured using an homogenous mobility shift assay (HMSA; Prometheus Lab, San Diego, United States). Blood samples were considered positive for AAA presence if ≥1.7 U/mL. Disease activity was assessed at the same points by means of the Harvey-Bradshaw Index (HBI, remission 16). Moreover, endoscopic activity was assessed at baseline and at the time of relapse by means of CD endoscopic index (CDEIS 5 responder, CDEIS<3 complete endoscopic remission and mucosal healing). Results: We have data from 133 blood samples. AAA were observed in 26/133 (19.5%) samples, and 10/26 (38.5%) had a value of AAA ≥1.7 U/mL. TNF-α levels were present in all samples assessed (Mean 4.4, range 027.2). As shown in the figure, per-patient median TNF-α levels were strongly correlated with median HBI scores (r2=0.702, p<0.0001). Moreover, TNF levels were also correlated with CDEIS (r2=0.350, p=0.001). Conclusion: TNF-α levels strongly correlated with disease activity based on HBI and CDEIS indices in patients with CD in maintenance treatment with ADA. Indeed, moderate to severe patients often have high sustained TNF-α levels.