S3343 Biologic Therapy and Reactive Therapeutic Drug Monitoring in Patients with Inflammatory Bowel Disease and Primary Sclerosing Cholangitis

Introduction: Primary sclerosing cholangitis (PSC) is associated with inflammatory bowel disease (IBD). Patients with concomitant PSC-IBD are at higher risk for IBD-related dysplasia and malignancy, however, the typical clinical IBD course is less severe. Recent years have seen increased biologic therapy use in IBD. As such, therapeutic drug monitoring (TDM) has also seen increased use, with reactive (rTDM) and proactive (pTDM) strategies being implemented in clinical care. The aim of this study was to identify the prevalence of biologic use and rTDM in a cohort of PSC-IBD patients. Methods: Retrospective analysis of patients with PSC-IBD on biologic therapy who underwent rTDM from Jan. 2018 to Aug. 2020 at the University of Virginia. Demographic data including age, disease duration, and comorbidities were recorded. IBD categorizations were recorded according to the Montreal Classification. Treatment outcomes including therapy changes after TDM were obtained. Results: 157 patients with PSC-IBD were identified. Of these, 29 patients (19%) were treated with biologic therapy during the study period. 13 patients underwent rTDM due to primary or secondary loss of response. An additional patient who underwent pTDM was identified but not included in the analysis. Median duration of IBD in this group was 9 years, and the median duration of concomitant PSC-IBD was 5.2 years. 19 TDM tests were obtained in these 13 patients. Of these, sub therapeutic drug levels were found in ten, and three detected anti-drug antibodies. Seven showed appropriate trough levels. TDM resulted in a change to IBD therapy (i.e. dose escalation, change in biologic therapy used, or addition of IBD medication) in 16 out of 19 tests. The remaining two resulted in no change to current therapy. Conclusion: Herein we describe epidemiologic data of biologic use in PSC-IBD patients at an academic center. PSC-IBD is thought to have a less severe clinical presentation and course. However, our experience demonstrates that a subset of PSC-IBD patients exists which require biologic therapy and have a more aggressive clinical course. In this subset, an rTDM strategy showed a high incidence of sub therapeutic trough levels and anti-drug antibodies, leading to optimization or change in therapy in over 80% of rTDM instances. Data on pTDM was limited in this study. Future studies should explore whether a pTDM strategy yields improved clinical outcomes in this special subset of PSC-IBD patients with a more aggressive phenotype.Table 1.: Demographic and clinical data.