Modeling Trough Levels to Predict Optimal Infliximab Dosing

A recent study for optimizing infliximab  dosing: LE Bauman et al.  2019 Jul 9. pii: izz143. doi: 10.1093/ibd/izz143. [Epub ahead of print]

The authors identified 228 pediatric patients with IBD and developed a pharmocokinetic model using weight, albumin, sedimentation rate and antibodies to infliximab (ATI) to help predict infliximab dosing that would achieve a therapeutic trough level (>5 mcg/mL).

In their study, they also simulated 1000 patients and found that only 24% of patients receiving 5 mg/kg q8weeks achieved a therapeutic level; this increased to 56% for 10 mg/kg q8weeks.  Shortening dose interval more reliably achieved therapeutic levels: 5 mg/kg q4 weeks had a target level in 84% and 10 mg/kg q6 weeks had a target level in 80%.

The image above corresponds to Figure 5 in the manuscript.  This figure shows the difference between proactive and reactive dosing strategy.  In the first panel, a higher initial dose prevents suboptimal dosing whereas the second panel shows suboptimal troughs until adjustment of dose after identifying a low trough.  Avoiding low troughs may reduce the likelihood of developing antibodies to infliximab and therapeutic failure

My take: This study and several others indicate that most pediatric patients need either more frequent inflixmab dosing or higher initial doses to achieve therapeutic levels and to improve outcomes.

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