Background: Clinical use of therapeutic drug monitoring (TDM)-based strategies for infliximab (IFX) treatment is limited by lack of validated and well-defined cut-off points for IFX trough levels distinguishing between therapeutic and sub-therapeutic drug levels. This study aimed to identify serum IFX levels associated with clinical remission and biochemical remission during maintenance therapy to facilitate TDM-guided IFX therapy in patients with inflammatory bowel disease (IBD).
Methods: Retrospective cohort study including 149 IFX-naïve IBD patients (Crohn's disease (CD) n=83; ulcerative colitis (UC) n=66) who received IFX induction therapy followed by maintenance therapy every 8 weeks. Using a validated immunofluorometric assay IFX trough levels were measured in 647 blood samples which have routinely been collected prior to scheduled infusions from all anti-TNF treated IBD patients at a tertiary center from 2009 onwards. Treatment outcomes were assessed at the time of each infusion. Clinical remission was defined as Harvey-Bradshaw Index <4 or Partial Mayo Score <2. Blood C-reactive protein (CRP) <10 μg/mL defined biochemical remission. Results are based on data from serial blood samples at different time points throughout one year of follow up.
Results: Significantly higher IFX trough levels were observed in patients in clinical remission compared to those with active disease: Weeks 14 (p<0.0001), 22 (p<0.01), 30 (p<0.001), 38 (p=0.06), 46 (p<0.01) and 54 (p<0.01). At all time points during maintenance therapy, receiver operation characteristic (ROC) analyses showed that median IFX levels ≥3.5 μg/mL (cut-off value) were associated with clinical remission. Patients in biochemical remission also had significantly higher circulating trough levels of IFX as compared to those with active disease: Weeks 14 (p<0.01), 22 (p<0.01), 30 (p<0.001) and 38 (p<0.05), but not at weeks 46 and 54, likely reflecting a type 2 error. ROC analyses revealed that median IFX levels ≥2.1 μg/mL were associated with biochemical remission.
Conclusions: IFX blood trough levels ≥3.5 μg/mL is associated with beneficial treatment outcomes during the entire first year of IFX maintenance therapy. This therapeutic threshold can be used to support TDM-based treatment decisions when optimizing IFX treatment in IBD.