Systematic review with meta-analysis: association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases

Abstract

Background: There has been limited evaluation of the association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases (IBD).

Aim: To perform a systematic review and meta-analysis to evaluate the potential role of therapeutic drug monitoring (TDM) for vedolizumab.

Methods: Through a systematic literature search through 28 February 2019, we identified five cohort studies (558 patients, 42% with ulcerative colitis) reporting the association between vedolizumab trough concentration and clinical outcomes in patients with IBD. We calculated mean difference (MD) in vedolizumab trough concentration in patients achieving vs not achieving clinical outcomes, and qualitatively synthesized thresholds associated with favourable outcomes.

Results: In patients with UC, median vedolizumab trough concentrations were consistently higher in patients achieving clinical remission (median, 14.3 μg/mL vs 10.5 μg/mL; MD, 5.1 μg/mL, 95% CI, 2.8-7.4) or endoscopic remission (median, 13.0 μg/mL vs 9.7; MD, 5.1 μg/mL, 95% CI, 2.2-7.9). In patients with CD, there was no significant difference in median vedolizumab trough concentrations in patients achieving vs not achieving clinical remission (MD, 2.0 μg/mL; 95% CI, -0.5 to 4.5) or endoscopic remission (MD, 3.6 μg/mL; 95% CI, -1.4 to 8.6). In patients with UC, week 6 vedolizumab trough concentrations ≥18.5-20.8 μg/mL, and maintenance trough concentrations ≥9.0-12.6 μg/mL were associated with favourable clinical outcomes. Antibodies to vedolizumab were reported in 1.7%-3.0% patients on maintenance therapy.

Conclusion: Based on meta-analysis, patients with UC who achieve endoscopic and clinical remission have significantly higher vedolizumab trough concentration during maintenance therapy. Vedolizumab trough concentration >20 μg/mL at week 6, and >12 μg/mL during maintenance may be associated with better outcomes, though cause-effect relationship remains unclear. Prospective studies on reactive and proactive therapeutic drug monitoring of vedolizumab (vs empiric dose escalation) are warranted.

Figure 1.

Study selection flowchart

Figure 2.

Mean difference in vedolizumab trough concentrations (in μg/ml) in remitters vs. non-remitters in patients with UC

Figure 3.

Mean difference in vedolizumab trough concentrations (in μg/ml) in remitters vs. non-remitters in patients with CD

Figure 4.

Proposed algorithm for applying therapeutic drug monitoring for vedolizumab. Please note, proposed trough concentrations may vary depending on what treatment endpoint is being targeted (clinical response, clinical remission, endoscopic remission, histologic remission, etc.). LLQ refers to lower limit of quantification of vedolizumab assay. Upper limit of therapeutic target beyond which further escalation of therapy is very unlikely to be helpful, has not been well-identified; based on expert opinion, this threshold is probably >30μg/ml for week 6 level and >20μg/ml for maintenance trough concentration.