P0718Higher colonic tissue drug concentrations of subcutaneous compared to intravenous infliximab administration in patients with Inflammatory Bowel Disease

Abstract Background Intestinal drug concentrations in patients with inflammatory bowel disease (IBD0 under subcutaneous (SC) infliximab (IFX) therapy have not been investigated. Aim: We compared serum with tissue drug levels between patients with IBD treated with SC or intravenous (IV) IFX maintenance therapy. Methods Any IBD patients under stable dose SC or IV IFX maintenance therapy who underwent a colonoscopy were eligible. Clinical disease activity was defined by using clinical activity scores and biomarkers. Endoscopic disease activity was categorized as absent, or active graded as mild, moderate, or severe. Two biopsy specimens and a blood sample at the time of endoscopy were collected. Results In total 35 patients were enrolled. including 23 patients treated with SC (cohort SC) and 12 with IV IFX therapy (cohort IV) Serum and tissue drug levels were significantly higher in the SC IFX cohort compared with those in the IV cohort (22 µg/mL vs 9 µg/mL for serum; p 0.001 and 25 µg/g vs 10 mg/g for tissue; p = 0.002, respectively) (Fig 1). Similar positive correlations were found between serum and tissue drug levels for both IV and SC cohorts (r = 0.42; p = 0.014 and r = 0.43; p = 0.001, respectively). Tissue drug levels increased gradually from patients with no endoscopic activity to those with mild, moderate or severe endoscopic activity in both the IV and the SC cohort (both, p 0.001). A serum IFX level greater than 16.1 mg/mL was highly predictive of a tissue drug level 14 mg/g tissue (Sensitivity: 94 %, Specificity: 94 %). Tissue and serum drug concentration was associated significantly with sustained clinical remission with a threshold value of 17 µg/g (p 0.001) and 14.5 µg/mL(p:0.01) but should better tissue concentration could predict with more accuracy sustained clinical remission than serum drug levels (AUROC: 0.82 and 0.76 respectively) (Fig 2). Conclusion Serum and tissue drug IFX levels are positively correlated and are significantly higher in patients receiving SC compared to IV IFX. Tissue IFX concentration predicted strongly sustained clinical remission and should be interesting in clinical practice to optimize our patients. Conflict of interest: Prof. Dr. Roblin, Xavier: Abbvie, Celltrion, Amgen, Ferring, Takeda, Janssen, Biosynex, Pfizer Nancey, Stéphane: Abbvie, Janssen, Pfizer, Celltrion, Takeda, Amgen Fresenius Kabi, Sandoz, Lilly Barrau, Mathilde: Abbvie, Celltrion, Janssen Papamichail, Konstantinos: Personal Fees: Lecture fees from Physicians Education Resource LLC and Grifols scientific advisory board fees from ProciseDx Inc and Scipher Medicine Corporation. Other: Consultant for Prometheus Laboratories Inc. Cheifetz, Adam: Consulting and Scientific Advisory Board (SAB): Abbvie, Johnson and Johnson, Prometheus (SAB), Bisynex, Aegirbio (SAB), Artizan (SAB), Fzata, Celltrion, Eli Lilly, Adiso, BMS, Clario, Food is Good, Fresenius Kabi, Pfizer, Procise, Spherix, Samsung Speaking (non-branded): Abbvie, BMS, Johnson and Johnson Paul, Stephane: Biosynex, Celltrion, Pfizer, Takeda, Abbvie, Janssen