S0750 A Decade Long Trend of Therapeutic Drug Monitoring at a Tertiary Referral Center: Shifting Focus From Reactive to Proactive - Is This Useful?

Abstract

INTRODUCTION: Therapeutic drug monitoring (TDM) is routinely used for optimization of treatment of Crohn’s disease (CD) patients. There has been a gradual shift towards proactive TDM with its purported benefits of increasing drug levels, reducing loss of response from immunogenicity, and increasing the persistence of patients on infliximab (IFX). We herein report our experience at a tertiary referral IBD center on the trends of TDM since 2010 and determine the role it has played in the management of patients with CD. METHODS: This was a retrospective cohort study of CD patients who were exposed to IFX and had IFX trough/antibody levels (TDM) checked between 1/1/2010 and 11/31/2019. Variables assessed included demographics, disease behavior, surgical history, smoking history, prior anti-TNF exposure, IFX trough and antibody levels, IFX start and end dates, reasons for discontinuation, and pattern of TDM. Each TDM was classified as either proactive or reactive based on whether it was carried out as a response to loss of response (Reactive), or was it carried out at pre-defined time points to optimize drug levels (Proactive). RESULTS: Of a total of 1236 CD patients, 325 patients (median age at diagnosis 22 years, 56% men) were included. A total of 1,181 TDM assessments were carried out (892 proactive, 75%) with 24 immune-mediated events (15 immune-mediated loss of response, 9 infusion reactions) (Table 1). The frequency of proactive TDM increased across the study period with a concurrent decrease in rates of reactive TDM (P < 0.0001) (Figure 1). Similarly, the rate of IFX discontinuation decreased over the years (P < 0.0001) (Figure 2), whereas median IFX levels increased across the years (P < 0.0001) (Figure 3). On Kaplan Meier survival analysis, patients who underwent proactive assessment had a significantly lower IFX discontinuation rate compared to those who underwent reactive assessment (P < 0.0001) (Figure 4). CONCLUSION: In this large cohort of CD patients followed for 10 years at a tertiary IBD center we have observed an increase in the rate of proactive assessment for TDM. This has led to successively declining rates of IFX discontinuation and increased IFX drug levels. Furthermore, we observed that patients that were monitored proactively remained on IFX for longer periods of time. This study further advocates the need for gastroenterologists to incorporate proactive TDM in their day to day practice.Table 1.: TDM: Therapeutic drug monitoring, n: population, %: percentage, y: years, IQR: Inter-quartile range, CD: Crohn’s disease, IFX: Infliximab, Ab: antibodyFigure 1Figure 2