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* = Presenting author

P643 Therapeutic thresholds for infliximab trough levels during maintenance treatment in patients with inflammatory bowel disease

Rasmussen M.*1, Brynskov J.1, Ainsworth M.A.1, Buhl S.1, Bendtzen K.2, Steenholdt C.1

1Copenhagen University Hospital Herlev, Department of Gastroenterology, Herlev Copenhagen, Denmark 2Institute for Inflammation Research, Rigshospitalet, Copenhagen, Denmark

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.

Conclusion

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.