Division of Gastroenterology, University of California San Diego, La Jolla, California.
Division of Biomedical Informatics, University of California San Diego, La Jolla, California.
Aliment Pharmacol Ther. 2019 Oct;50(8):848-857. doi: 10.1111/apt.15484. Epub 2019 Sep 4.
There has been limited evaluation of the association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases (IBD).
To perform a systematic review and meta-analysis to evaluate the potential role of therapeutic drug monitoring (TDM) for vedolizumab.
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.
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.
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.
在炎症性肠病（IBD）患者中，vedolizumab 谷浓度与临床结局之间的关联已得到有限评估。
进行系统评价和荟萃分析，以评估 vedolizumab 的治疗药物监测（TDM）的潜在作用。
通过系统文献检索，我们于 2019 年 2 月 28 日确定了五项队列研究（558 例患者，42%为溃疡性结肠炎），报告了 IBD 患者 vedolizumab 谷浓度与临床结局之间的关联。我们计算了达到和未达到临床结局的患者之间 vedolizumab 谷浓度的均数差（MD），并定性综合了与有利结局相关的阈值。
在 UC 患者中，达到临床缓解（中位数 14.3μg/mL 比 10.5μg/mL；MD 5.1μg/mL，95%CI 2.8-7.4）或内镜缓解（中位数 13.0μg/mL 比 9.7；MD 5.1μg/mL，95%CI 2.2-7.9）的患者的 vedolizumab 谷浓度中位数始终较高。在 CD 患者中，达到临床缓解（MD 2.0μg/mL；95%CI -0.5 至 4.5）或内镜缓解（MD 3.6μg/mL；95%CI -1.4 至 8.6）的患者的 vedolizumab 谷浓度中位数无显著差异。在 UC 患者中，第 6 周 vedolizumab 谷浓度≥18.5-20.8μg/mL，维持治疗时谷浓度≥9.0-12.6μg/mL 与有利的临床结局相关。在维持治疗中，有 1.7%-3.0%的患者报告有 vedolizumab 抗体。
基于荟萃分析，达到内镜和临床缓解的 UC 患者在维持治疗期间的 vedolizumab 谷浓度明显更高。第 6 周时谷浓度>20μg/mL，维持时>12μg/mL 可能与更好的结局相关，但因果关系尚不清楚。需要前瞻性研究 vedolizumab 的反应性和主动性治疗药物监测（与经验性剂量递增相比）。
