Influence of Drug Exposure on Vedolizumab-Induced Endoscopic Remission in Anti-Tumour Necrosis Factor [TNF] Naïve and Anti-TNF Exposed IBD Patients

Abstract

Background and Objectives Vedolizumab has demonstrated efficacy and safety in patients with Crohn's disease [CD] and ulcerative colitis [UC]. Endoscopic outcome data are limited, especially in anti-tumour necrosis factor [TNF] naïve patients. The present study compared endoscopic outcome in anti-TNF naïve and exposed patients, and explored if this was affected by drug exposure. Methods We retrospectively analysed all patients initiating vedolizumab at our tertiary referral centre since 2015. For UC, endoscopic improvement was defined as a Mayo endoscopic subscore ≤1 at week 14. For CD, endoscopic remission was defined as absence of ulcerations at week 22. Vedolizumab trough concentrations were measured at week 6, week 14 and during maintenance. Results A total of 336 patients were identified [53.3% CD], 20% of them being anti-TNF naïve. Endoscopic improvement was achieved by 56.1% of UC patients and endoscopic remission by 39.1% of CD patients. Endoscopic outcomes were significantly better in anti-TNF naïve vs exposed patients [all: 67.2% vs 42.0%, p = 0.0002; UC: 74.4% vs 50.0%, p = 0.02; CD: 57.1% vs 35.8%, p = 0.03]. Achievement of endoscopic end points significantly impacted long-term treatment continuation [p = 9.7 × 10−13]. A better endoscopic outcome was associated with significantly higher drug exposure in both CD and UC. Conclusions The results of this observational, single-centre real-life study suggest that vedolizumab may induce endoscopic remission in both CD and UC. Although anti-TNF naïve patients had a significantly better outcome, 42% of anti-TNF exposed patients still benefited endoscopically. A clear exposure–endoscopic response relationship exists, but not all patients will benefit from treatment intensification. Hence, predictive biomarkers remain necessary. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

Vedolizumab Trough Levels in Children With Anti‐Tumor Necrosis Factor Refractory Inflammatory Bowel Disease

“…The remission rates reported in adult studies are higher than the rates observed in the children in our cohort (17,24), which may be explained by inclusion of anti-TNF refractory PIBD patients only, whereas this was not the case in the adult studies. This is supported by studies showing significantly better outcomes in anti-TNF-naïve IBD patients (25)(26)(27) explanation for loss of response to anti-TNF, our data do not suggest that nonresponse or loss of response to VDZ can be explained by the formation of antibodies to VDZ (28). This is consistent with studies in adults that indicate immunogenicity to occur in <5% of cases (17,29).…”

A clinical decision support tool may help to optimise vedolizumab therapy in Crohn’s disease

“…Multiple studies in patients with active CD have shown a correlation between VDZ exposure and response, and higher clinical and endoscopic remission rates when stratified by drug exposure. [4][5][6][7][8][9][10] These findings hold out the possibility that dose intensification in patients with low VDZ trough concentrations during induction may result in higher remission rates. In support of this notion, observational data suggest that empiric administration of an additional drug dose in patients with suboptimal response to induction may improve outcomes.…”

“…Multiple studies in patients with active CD have shown a correlation between VDZ exposure and response, and higher clinical and endoscopic remission rates when stratified by drug exposure . These findings hold out the possibility that dose intensification in patients with low VDZ trough concentrations during induction may result in higher remission rates.…”

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

“…Both agents are have lower immunogenicity compared to anti-TNF [50], and the presence of ADA has not been consistently associated with therapy inefficacy in registration trials [122][123][124][125]. Early vedolizumab TLs (mainly at weeks 6 and 14) have been variously associated with clinical remission [101,102], treatment persistence [103], biochemical remission [103][104][105], endoscopic response [126], mucosal healing [104,105] and even histological healing [106]; due to the heterogeneity of assays used, timepoints assessed and outcomes investigated, different threshold concentrations have been proposed. An association between vedolizumab TLs during maintenance periods and treatment outcomes has been reported in multiple observational studies [102,106,107].…”