AT DDW 2016
SAN DIEGO (FRONTLINE MEDICAL NEWS) – A new study in a real-world patient cohort at a single center provides some guidance as to how to optimize infliximab dosing in patients with inflammatory bowel disease (IBD). The study identified factors that influence infliximab clearance, as well as those that influence the development of antibody titers to infliximab (ATI), which interfere with the efficacy of infliximab.
ATI, high body weight, and low serum albumin were found to significantly increase infliximab clearance.
“This has been shown before. A new finding is that prior exposure to anti-TNFs is also associated with increased infliximab clearance,” said presenting author Dr. Johannan Brandse, Academic Medical Center, Amsterdam.
The study also showed that infliximab exposure less than 3 mcg/mL increases the risk of developing ATI fourfold. “Below this concentration, antibodies develop and they are cumulative over time. Above this cutoff, patients do not develop ATI,” Dr. Brandse said at the annual Digestive Disease Week.
“Lower serum infliximab concentrations with undetectable ATI titers may be an early signal of upcoming detectable ATIs,” he suggested.
A retrospective pharmacokinetic study looked at patients with IBD. Among 332 IBD patients (253 with Crohn’s disease and 79 with ulcerative colitis), 997 infliximab concentrations and 756 ATI measurements were obtained using an ELISA and antigen-binding test. Eighty percent received infliximab as their first anti-TNF agent; 43% were on concomitant immunomodulatory therapy.
Data were collected on sex, weight, disease location and behavior, infliximab dose, immunomodulators, albumin, and serum C-reactive protein.
ATIs were detected in 75 of 332 patients (23%). On multivariate analysis, factors associated with infliximab clearance were ATI titers greater than 30 antibody units per mL (consistently associated with undetectable infliximab concentrations), high body weight, low serum albumin, and anti-drug antibody titer.
Next, the investigators developed a pharmacokinetic model using these factors and found that they could accurately predict serum pharmacokinetic concentrations and the development of ATI. “Identification of influential pharmacokinetic and ATI factors improves the prediction of infliximab levels, potentially allowing for individualized dosing and cost reduction,” he stated.
Dr. Brandse reported no financial disclosures.