Elliot J. Graziano, MD1, Katherine Gheysens, MD2, Raymond K. Cross, MD, MS3, James Campbell, MD1, Byron Vaughn, MD1
1University of Minnesota, Minneapolis, MN; 2University of Maryland, Baltimore, MD; 3University of Maryland Medical Center, Baltimore, MD
Introduction: Therapeutic drug monitoring (TDM) of biologic therapies is increasingly used in the management of inflammatory bowel disease (IBD). It is established that for anti-tumor necrosis factor medications, a dose escalation will have a positive clinical response in up to 86% of those with low serum drug concentrations. However, it is unknown if trough concentration predicts response to VDZ dose escalation. The objective of this study was to evaluate the impact of TDM on clinical outcomes in patients with IBD treated with VDZ.
Methods: This was a retrospective study of patients with IBD treated at two institutions (University of Minnesota, University of Maryland) with VDZ who had a VDZ trough concentration post induction between November 2016 and October 2018. A positive response was defined as improvement in the factor that was the etiology of dose escalation and categorized as clinical response, biomarker (i.e. CRP) response, or endoscopic response. An a priori VDZ trough concentration of 10 ug/ml was chosen as the cut off for a low level. Data was collected including demographics, disease characteristics, management changes and outcomes. VDZ concentration was performed using a commercial test (Inform Diagnostics, Irving, TX). Student’s t-test and Fisher's exact test were used for continuous and categorical variables respectively in JMP Pro 14.0.0.
Results: 48 trough concentrations were obtained in 43 patients. 51.2% had Crohn’s disease while 48.8% had ulcerative colitis/indeterminate colitis. Following TDM, 62.5% (30/48) of patients underwent a dose change: 23 dose escalations, 5 stoppages and 2 dose de-escalations. 65% (13/20) of dose escalations (3 had inadequate follow-up) had a positive response to dose adjustment: 8 symptomatic response, 1 biologic response and 4 endoscopic response. Among those with a low VDZ trough < 10 ug/ml, 75% (9/12) improved following dose escalations versus 50% (4/8) of those with VDZ trough ≥10 ug/ml (p=0.356). The mean CRP prior to dose escalation was 7.0 mg/L (SD=10.2) compared to 6.4 mg/L post dose escalation (SD=12.3) (p=0.863).
Discussion: TDM in VDZ results in frequent clinical management changes. While there was a greater percentage of patients that demonstrated clinical improvement following dose escalation with low drug levels, the difference was not statistically significant. Larger cohorts are needed to evaluate the impact of TDM with VDZ as our study was underpowered to identify small to moderate differences based on the pre-determined low VDZ level.
Citation: Elliot J. Graziano, MD; Katherine Gheysens, MD; Raymond K. Cross, MD, MS; James Campbell, MD; Byron Vaughn, MD. P0474 - OUTCOMES FOLLOWING THERAPEUTIC DRUG MONITORING OF VEDOLIZUMAB. Program No. P0474. ACG 2019 Annual Scientific Meeting Abstracts. San Antonio, Texas: American College of Gastroenterology.