Vedolizumab Serum Trough Concentrations and Response to Dose Escalation in Inflammatory Bowel Disease

Abstract

Serum vedolizumab concentrations are associated with clinical response although, it is unknown if vedolizumab concentrations predict response to dose escalation. The aim of this study was to identify if vedolizumab trough concentrations predicted the response to vedolizumab dose escalation. We assessed a retrospective cohort of patients on maintenance vedolizumab dosing at five tertiary care centers with vedolizumab trough concentrations. Multivariate logistic regression was used to control for potential confounders of association of vedolizumab concentration and clinical status. Those who underwent a dose escalation were further examined to assess if vedolizumab trough concentration predicted the subsequent response. One hundred ninety-two patients were included. On multivariate analysis, vedolizumab trough concentration (p = 0.03) and the use of immunomodulator (p = 0.006) were associated with clinical remission. Receiver operator curve analysis identified a cut off of 7.4 μg/mL for clinical remission. Of the fifty-eight patients with dose escalated, 74% of those with a vedolizumab concentration <7.4 μg/mL responded versus 52% of those with a vedolizumab trough concentration ≥7.4 μg/mL (p = 0.08). After adjustment for relevant confounders, the odds ratio for response with vedolizumab concentration <7.4 μg/mL was 3.7 (95% CI, 1.1–13; p = 0.04). Vedolizumab trough concentration are associated with clinical status and can identify individuals likely to respond to dose escalation. However, a substantial portion of patients above the identified cut off still had a positive response. Vedolizumab trough concentration is a potentially helpful factor in determining the need for dose escalation in patients losing response.

Proposed pathway for therapeutic drug monitoring and dose escalation of vedolizumab

“…In a multicentre retrospective study of 58 patients with IBD with secondary LOR to vedolizumab, 62% of the study group responded to reactive dose escalation, and those with lower trough levels were more likely to respond 24. Similar response rate was reported in real-life settings 25.…”

Effect of vedolizumab dose intensification on serum drug concentrations and regain of response in inflammatory bowel disease patients with secondary loss of response

“…The authors suggested that if a patient is not responding to VDZ maintenance treatment, dose escalation should be considered in order to achieve a VDZ concentration of at least 11.5 µg/mL 22 . Also, Vaughn at al found that after dose escalation, 74% of those with a VDZ concentration <7.4 µg/mL responded versus 52% of those with a VDZ trough concentration ≥7.4 µg/mL; however, this was not significant ( P = 0.08) 23 …”

Predictors and Early Markers of Response to Biological Therapies in Inflammatory Bowel Diseases

“…An association between vedolizumab TLs during maintenance periods and treatment outcomes has been reported in multiple observational studies [ 102 , 106 , 107 ]. Interestingly, in a retrospective analysis of IBD patients on maintenance therapy with vedolizumab, TLs <7.4 µg/mL, in patients experiencing LOR was associated with a significantly increased likelihood to respond to dose escalation compared to higher concentrations (OR 3.7, 95% CI 1.1–13, p = 0.04) [ 108 ]. A similar exposure-efficacy relationship has been observed for ustekinumab: early TLs (week 4 and 8) have been associated with clinical remission [ 109 , 110 ], decrease of faecal calprotectin [ 111 ] and biochemical remission [ 112 ], while TLs during maintenance have been correlated with clinical remission [ 109 , 110 ], endoscopic response [ 111 , 113 ] and need for optimization [ 114 ].…”