Vedolizumab Levels During Induction Are Associated With Remission in Patients With Inflammatory Bowel Diseases: 2017 Category Award (IBD): 2017 Presidential Poster Award

Introduction: There is limited data on the role of therapeutic drug monitoring (TDM) in patients receiving therapy with vedolizumab for Crohn's disease (CD) or ulcerative colitis (UC). The aim of this study was to assess the relationship of serum vedolizumab trough levels (VTL) during induction and disease remission after 22 weeks of therapy. We also sought to investigate the presence of antibodies to vedolizumab (ATV). Methods: Prospective cohort study including patients with active UC and CD starting therapy with vedolizumab. Predictive variables included demographics, VTL and ATV (measured using a validated drugtolerant assay at weeks 2, 6 and 14), C-reactive protein (CRP), albumin level, Harvey Bradshaw index (HBI) in CD and Mayo Clinical Score (MCS) in UC. Simple endoscopic score-CD (SES-CD) in CD and Mayo endoscopic score (MES) in UC. Primary outcome was disease remission at week 22, defined as an HBI < 5 (in CD)/MCS < 3 (in UC), normal CRP and SES-CD≤2 (in CD) or MES≤1 (in UC). Secondary outcome was steroid-free remission (SFR) defined as remission while off steroids at week 22. Results: Forty-five patients were included. VTL at weeks 2, 6 and 14 were higher on those patients that had achieved remission at week 22, even though only the difference at weeks 2 and 6 were statistically significant (Figure 1). VTL at weeks 2 and 6, and baseline albumin level best correlated with remission (Table 1). Patients with a VTL ≥24 ug/mL (second quartile of week 2 VTL) at week 2 and ≥ 10.6 (first quartile of week 6 VTL) were more likely to be in remission at week 22 (OR: 5 [95%CI:1.4-17.8], p:0.001 and OR: 13.5 [95%CI: 1.5-118.7], p=0.005 respectively). Three patients had detectable ATV - none of them were on an immunomodulator: one patient at week 2 and the other two at week 6. All antibodies became negative by week 14. Patients that were receiving immunomodulators in combination with vedolizumab had higher VTL at weeks 2, 6 and 14, even though only the difference at week 2 reached statistical significance (Figure 2). Patients with CD were more likely to be on combination therapy and had lower VTL at week 2 (Table 2).Figure: Vedolizumab levels at weeks 2, 6 and 14 in patients with and without remission at week 22.Figure: Trough vedolizumab levels by week in patients on and off combination therapy.Table: Table. Correlation between study variables and disease remission at week 22Table: Table. Differences between patients with Crohn's disease and ulcerative colitisConclusion: Higher vedolizumab levels during induction are associated with better response to therapy at week 22 and are correlated with remission while the rate of immunogenicity against vedolizumab was low and transient. TDM may have a role in patients with CD or UC receiving vedolizumab and early optimization may potentially be of benefit in these patients.