Success and safety of high infliximab trough levels in inflammatory bowel disease

• Published in: Scandinavian journal of gastroenterology Vol. 53; no. 8; pp. 940 - 946
• Main Authors: Drobne, David, Kurent, Tina, Golob, Sasa, Svegl, Polona, Rajar, Polona, Terzic, Sara, Kozelj, Matic, Novak, Gregor, Smrekar, Natasa, Plut, Samo, Sever, Nejc, Strnisa, Luka, Hanzel, Jurij, Brecelj, Jernej, Urlep, Darja, Osredkar, Josko, Homan, Matjaz, Orel, Rok, Stabuc, Borut, Ferkolj, Ivan, Smid, Alojz
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03-08-2018
• Subjects: Adolescent; Adult; Biomarkers - analysis; C-Reactive Protein - analysis; combination treatment; Cost-Benefit Analysis; cost-effectiveness; Drug Monitoring - methods; Feces - chemistry; Female; Humans; Inflammatory Bowel Diseases - drug therapy; Infliximab - administration & dosage; Infliximab - pharmacokinetics; infliximab-induced skin manifestations; Leukocyte L1 Antigen Complex - analysis; Logistic Models; Male; Multivariate Analysis; Prospective Studies; Remission Induction; Slovenia; switch; Therapeutic drug monitoring; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Young Adult; Therapeutic drug monitoring; cost-effectiveness; combination treatment; infliximab-induced skin manifestations; switch
• ISSN: 0036-5521; 1502-7708
• DOI: 10.1080/00365521.2018.1486882

Objective: A prospective trial suggests target infliximab trough levels of 3-7 μg/mL, yet data on additional therapeutic benefits and safety of higher trough levels are scarce.
Aim: To explore whether high infliximab trough levels (≥7 μg/mL) are more effective and still safe.
Material and methods: In this cohort study of 183 patients (109 Crohn's disease and 74 ulcerative colitis) on infliximab maintenance treatment at a tertiary referral center we correlated fecal calprotectin and C-reactive protein to trough levels (426 samples) at different time points during treatment. Rates of infections were compared in quadrimesters (four-month periods) with high trough levels to quadrimesters with trough levels <7 μg/mL during 420 patient-years.
Results: Fecal calprotectin and C-reactive protein (median [interquartile range]) were lower in patients with high trough levels (fecal calprotectin 66 mg/kg [30-257]; C-reactive protein 3 mg/L [3-3]) compared to trough levels below 7 μg/mL (fecal calprotectin 155 mg/kg [72-474]; C-reactive protein 3 mg/L [3-14.5]) (p < .001). High trough levels were superior also after excluding samples with trough levels <3 μg/mL from analysis. No differences in rates of infections were observed in quadrimesters with high trough levels (16/129 [12.4%]) compared to quadrimesters with trough levels <7 μg/mL (32/344 [9.3%]) (p = .32). Maintaining high trough levels resulted in 32% (interquartile range: 2-54%) increase of infliximab consumption.
Conclusion: High infliximab trough levels provide better control of inflammation in inflammatory bowel disease without increasing the risk of infection.