Baseline infliximab clearance identifies patients requiring intensified induction in acute severe ulcerative colitis

Background Infliximab (IFX) is used for steroid-refractory acute severe ulcerative colitis (ASUC). We assessed whether baseline IFX clearance (CL) prior to rescue therapy was associated with the use of intensified induction and treatment outcomes. Methods Retrospective cohort study including patients with ASUC treated with IFX at two tertiary Danish inflammatory bowel disease centres. Baseline IFX CL (L/day) was estimated using a pharmacokinetic model incorporating gender, albumin and antidrug antibodies. Results Baseline IFX CL was significantly higher by 30% in patients with ASUC (n=74) versus outpatients (n=90) (median 0.456 vs 0.350, p<0.001). Intensified IFX induction was used in 26 (35%) patients with ASUC versus no outpatients. Intensified patients with ASUC had significantly higher CL by 18% (0.52 vs 0.44, p<0.01). IFX CL ≥0.42 identified by the Youden Index is associated with intensification (area under the receiver operating characteristic curve (AUC ROC ) 0.69 (0.56–0.81), 0.003; sensitivity 0.89 (0.69–0.92), specificity 0.45 (0.13–0.62)). CL was the only variable consistently associated with intensification in univariable and multivariable analyses whereas albumin showed only modest discriminatory performance. Among non-intensified patients with ASUC, those with high baseline IFX CL above the threshold (≥0.42) had numerically higher 1-year colectomy rates than those with low CL (5/27 (19%) vs 1/21 (5%); p=0.20). Conversely, colectomy rates were similar with intensification irrespective of high or low CL (35% vs 33%, p=1.00). Treatment outcomes were comparable regardless of CL in patients avoiding colectomy. Conclusion Baseline IFX CL was associated with the use of intensified induction in ASUC. High baseline IFX CL prior to therapy initiation may identify patients at risk of insufficient response to standard induction strategies. Prospective validation of CL-guided dosing is warranted.