P1078High baseline infliximab clearance in patients with acute severe ulcerative colitis predicts need for dose intensification to achieve treatment outcomes comparable to patients with low clearance

Abstract Background Acute severe ulcerative colitis (ASUC) results in colectomy in 15% of patients.​1​ This study investigated if baseline infliximab (IFX) clearance (CL) prior to initiation of IFX rescue therapy associated with use of intensified induction regimen as well as treatment outcomes. Methods Retrospective cohort study from 2 tertiary IBD centres including all ASUC patients receiving IFX rescue therapy. Baseline IFX CL prior to initiation of IFX was estimated by a previously published model: IFX CL = 0.407 * (albumin/4.1)-1.54 * 1.471Antibody status (per see =0) * 0.764 sex (male=0; female=1). ​2​ IFX induction intensification (increased dosing 5 mg/kg and/or shortened dosing intervals deviating from weeks 0, 2, 6) was defined by the treating physician. Results Twenty-seven (33%) of 82 ASUC patients received an intensified IFX induction regimen based on clinical assessment of need. Baseline IFX CL was significantly higher in intensified compared to non-intensified patients (median 0.519 L/day, IQR 0.434–0.626 vs. 0.440, 0.386–0.519; p = 0.008). There was no significant difference in baseline IFX CL between ASUC patients complying with Truelove Witt criteria or not (0.477 L/day, 0.397-0.567 vs. 0.440, 0.397-0.509; p = 0.25). ROC analysis (AUCROC 0.69 0.56-0.81, p = 0.003) with Youden Index identified a threshold of ≥ 0.419 L/day to optimally predict use of intensified IFX induction regimen (sensitivity 0.89 0.69-92, specificity 0.45 0.13-0.62). Lower baseline albumin did not associate with treatment intensification (OR 0.35 0.11-0.98, p = 0.06. AUCROC 0.63 0.49-0.77, p = 0.053). Both univariable and multivariable analyses identified IFX CL as the only significant factor associated with intensification. Among non-intensified ASUC patients, those with high IFX CL above the identified threshold (≥0.419 L/day) had numerically higher risk of colectomy as compared to patients with low IFX CL at 3 and 12 months (both: n = 5/27, 19% vs. 1/21, 5%; p = 0.21). Notably, among intensified ASUC patients, those with high IFX CL had similar risk of colectomy as compared to patients with low IFX CL at 3 months (n = 6/23, 26% vs. 1/3, 33%; p = 1.00) and 12 months (n = 8/23, 35% vs. 1/3, 33%; p = 1.00). IFX treatment persistence and clinical remission was similar between intensified and non-intensified ASUC patients at 3 months (56% vs. 80%, p = 0.05 and 64% vs. 59%, p = 1.00) and 12 months (34% vs. 54%, p = 0.20 and 100% vs. 78%, p = 0.30). Conclusion In ASUC, baseline IFX CL associate with treatment intensification according to clinical judgement. Our data indicate that patients with high baseline IFX CL have increased risk of colectomy if a standard IFX induction regimen is used but a favourable prognosis once intensification is applied. References: 1. Li Wai Suen AC, De Cruz P, Laharie D, et al. Review Acute Severe Ulcerative Colitis Management: Unanswered Questions and Latest Insights. www.thelancet.com/gastrohep ​ 2. Fasanmade AA, Adedokun OJ, Ford J, et al. Population pharmacokinetic analysis of infliximab in patients with ulcerative colitis. Eur J Clin Pharmacol. 2009;65(12):1211-1228. doi:10.1007/s00228-009-0718-4​ Conflict of interest: Nissen, Mathilde Jepsen: No conflict of interest Andersen, Frederik Ørtoft: No conflict of interest Ovesen, Pernille Dige: No conflict of interest Ainsworth, Mark Andrew: No conflict of interest Kjeldsen, Jens: No conflict of interest Steenholdt, Casper: Lectures for Takeda, MSD and Janssen-Cilag research grant from Takeda.