Infliximab trough levels above 7 μg/mL in inflammatory bowel disease treated with infliximab: Better control of inflammation without increased risk of infections Drobne D, Kurent T, Golob S, et al. Slides compiled by Sharyle Fowler UEGW 2017

Introduction Background and objectives Methods The IFX target trough level for optimal control is not clear; previous studies have suggested 3–7 μg/mL1 Objective: To explore whether IFX trough levels > 7 μg/mL are more effective and still safe compared with lower levels Methods Single-centre cohort in Slovenia of 183 patients (CD: 109, UC/IBD-U: 74; adults: 162, children: 21) who received IFX between 2010–2015 Efficacy was assessed using FCP, CRP and endoscopy Infection rates were assessed over 4-month intervals IFX trough levels were available in 473/1260 (38%) of the 4-month periods CD: Crohn’s disease; CRP: C-reactive protein; FC: fecal calprotectin IBD-U: inflammatory bowel disease unclassified ; IFX: infliximab 1. Vande Casteele N, et al. Gastroenterology 2015;148:1320-1329.e3..

Infliximab trough levels Results: Efficacy Median FCP and CRP were significantly lower in patients with high (≥ 7 μg/mL) compared with low (< 7 μg/mL) IFX trough levels Median FCP: 66 (IQR 30–257) vs 155 mg/kg (IQR 72–474), p <0.001, respectively Median CRP: 3 (IQR 3–3) vs 3 mg/L (IQR 3–14.5), p < 0.001, respectively More patients had increased CRP and FCP with lower IFX levels (< 7 μg/mL) FCP/CRP normalized in 10/17 patients after dose optimization to increase trough levels from 3–7 to > 7 μg/mL Infliximab trough levels  ≥ 7 µg/mL < 7 µg/mL p value Increased CRP (> 3 mg/L), n (%) 20 (20) 113 (40) < 0.001 Increased FCP(> 100 mg/kg), n (%) 17 (45) 51 (67) 0.022 CRP: C-reactive protein; FCP: fecal calprotectin; IFX: infliximab

Results: Safety During follow-up, there were 160 infections that necessitated postponing IFX infusion There were no differences in rates of infection between 4-month periods based on IFX levels < 7 vs ≥ 7 μg/mL (9.3% vs 12.4%, p = 0.32) , respectively There were no differences in median IFX trough levels in 4-month periods with vs without infection (4.25 vs 4.09 μg/mL, p = 0.867) IFX: infliximab

Conclusions & significance to clinical practice Although the study does not determine a target IFX trough level, it provides evidence that serum trough concentrations above the frequently quoted 3–7 μg/mL target may be beneficial in some patients without increasing risk of adverse events Significance to clinical practice IFX: infliximab