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Systematic review with meta‐analysis: association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases
Author(s) -
Singh Siddharth,
Dulai Parambir S.,
Vande Casteele Niels,
Battat Robert,
Fumery Mathurin,
Boland Brigid S.,
Sandborn William J.
Publication year - 2019
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.15484
Subject(s) - vedolizumab , medicine , ulcerative colitis , gastroenterology , trough concentration , therapeutic drug monitoring , trough level , cohort , inflammatory bowel disease , cohort study , dosing , disease , pharmacokinetics , transplantation , tacrolimus
SUMMARY 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.