High infliximab trough levels provide better control of inflammation in inflammatory bowel disease without increasing the risk of infection.

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Background In 2018, the European Medicines Agency (EMA) replaced a fixed 50 mg every 4-week maintenance regimen of golimumab for ulcerative colitis (UC) patients weighing <80 kg with new, flexible dosing that allows reactive dose optimization to 100 mg if clinically needed. We analyzed the endoscopic remission rates and pharmacokinetics of this new dosing regimen in real-life settings. Methods We prospectively recruited 30 consecutive (17 with body weight <80 kg) patients with UC who received golimumab with the new EMA label. The primary endpoint was endoscopic remission (Mayo ≤1) assessed by centrally-read endoscopy at week 14 and year 1. Golimumab concentrations, measured at nine prespecified timepoints, were correlated with endoscopic remission and identified cut-offs. Results Endoscopic remission was achieved in 15/30 (50%) and 10/30 (33%) patients at week 14 and year 1, respectively. Reactive dose optimization to 100 mg maintenance was needed in 13/17 (76%) patients. Golimumab concentrations at week 6 predicted week 14 and year 1 endoscopic remission. Week 6 concentrations >10.7 µg/ml were a strong predictor for achievement and maintenance of endoscopic remission during the first year of treatment, while concentrations <5.1 µg/ml identified the opposite. Conclusion One-third of the patients reached and maintained endoscopic remission during the first year of golimumab treatment, but the need for dose optimization to 100 mg every 4 weeks of maintenance was high in patients weighing <80 kg. Golimumab concentrations <5.1 µg/ml at week 6 identified patients who are unlikely to reach and maintain endoscopic remission with the new, flexible EMA label.

Background: Combination treatment with azathioprine for 6-12 months is the preferred strategy for starting infliximab due to improved pharmacokinetics. However, optimised infliximab monotherapy with proactive dose escalations in case of low trough levels is a potentially safer but under-studied alternative.Aim: To compare the clinical success and infliximab consumption of combination vs optimised monotherapy strategies.Methods: We studied the clinical success and infliximab consumption with both strategies in 149 patients (94 Crohn's disease; 55 ulcerative colitis) starting infliximab and undergoing intensive drug monitoring assisted treatment optimisation.Results: The drug retention rates were similar for optimised monotherapy and combination treatment after induction (96% vs 97%, P = 0.73), after the first year (90% vs 83%, P = 0.23) and at the end of follow-up (74% vs 75%, P = 0.968). Similarly, no significant differences were observed for steroid use at year 1 (5% vs 14%, P = 0.08) or mucosal healing at the end of follow-up (64% vs 67%, P = 0.8). Higher infliximab consumption (7.6 mg/kg q8 weeks [interquartile range (IQR): 5.9-10.3] vs 6.4 mg/kg q8 weeks [IQR: 5.2-8.0], P = 0.019) combined with lower trough levels (1.7 µg/mL [IQR: 0.3-6.6] vs 5.0 µg/mL [2.5-8.7], P = 0.012) resulted in almost 3-fold higher drug-to-trough ratio (3.9 vs 1.5) in monotherapy compared to combination strategy at year 1. At the end of follow-up, when azathioprine had been discontinued for a median of 14 [IQR: 3-33] months, these differences disappeared. Conclusions:In this study, optimised infliximab monotherapy was as clinically effective as combination therapy, but was associated with significantly higher infliximab consumption. The infliximab-sparing effect disappeared after azathioprine withdrawal.

Background The relationship between vedolizumab trough levels and combined endoscopic and clinical remission is unknown. Objective To compare vedolizumab trough levels in patients with and without combined remission within the first year of treatment. Methods We prospectively collected vedolizumab trough levels in 51 consecutive patients (28 Crohn's disease (CD) and 23 ulcerative colitis (UC)) before all infusions up to week 22, and at weeks 38 and 54, with concentrations measured after study completion. Centrally read endoscopy was performed at a median of 46 weeks. The primary outcome was combined endoscopic (CD: Simple endoscopic score for CD (SES-CD) < 4 without ulceration; UC: Mayo endoscopic subscore ≤ 1) and clinical remission (CD: resolution of abdominal pain; UC: resolution of rectal bleeding; both: resolution of altered bowel habit). Results Median vedolizumab trough levels at weeks 6 (25.7 vs 15.6 µg/mL; P = 0.015) and 22 (15.1 vs 4.9 µg/mL; P = 0.001) were higher in patients with combined remission. A threshold of 22 µg/mL at week 6 (area under the curve (AUC) 0.733; 95% confidence interval 0.567–0.899) and 8 µg/mL at week 22 (AUC 0.819; 95% confidence interval 0.692–0.946) predicted combined remission. Conclusion Early vedolizumab trough levels predicted combined endoscopic and clinical remission highlighting their possible use in clinical practice.