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

Abstract

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.

Keywords:

• Therapeutic drug monitoring
• switch
• cost-effectiveness
• infliximab-induced skin manifestations
• combination treatment

Acknowledgments

The authors thank Carmen Bobnar Sekulic, Tadeja Polanc, Valentina Savric and Mateja Kernjak Slak for help with data collection.

Disclosure of interest

David Drobne has served as a speaker, a consultant and an advisory board member for MSD, Abbvie, Takeda, Pfizer, Janssen, Krka. Gregor Novak has served as a speaker, a consultant and an advisory board member for Takeda, MSD, Abbvie, Dr. Falk Pharma, Ferring, Pfizer. Jernej Brecelj has served as a speaker for MSD and has received travel grants from Abbvie, Actelion Pharmaceuticals, Alexion Pharmaceuticals, and Falk Foundation. Rok Orel has served as a speaker, a consultant and an advisory board member for Nutricia, Biogaia, Medis, Dr. Falk Pharma, MSD, Abbvie, and Sandoz-Lek. Ivan Ferkolj has served as a speaker, a consultant and an advisory board member for MSD, Abbvie, Takeda and Krka. Borut Štabuc has served as a speaker, a consultant and an advisory board member for Krka, Bayer, Takeda and has received research funding from Krka.