Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA lol.
Department of Pharmacy, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
Inflamm Bowel Dis. 2024 Apr 3;30(4):660-670. doi: 10.1093/ibd/izad065.
Optimizing therapy and monitoring response are integral aspects of inflammatory bowel disease treatment. We conducted a systematic review and meta-analysis to determine whether serum ustekinumab trough concentrations during maintenance therapy were associated with ustekinumab treatment response in patients with inflammatory bowel disease.
A systematic review was performed to March 21, 2022, to identify studies using MEDLINE, EMBASE, and the Cochrane library. We included studies that reported the association between serum ustekinumab trough concentrations with clinical or endoscopic remission. Outcome measures were combined across studies using the random-effects model with an odds ratio (OR) for binary outcomes of endoscopic and clinical remission.
We identified 14 observational studies that were included in the analysis for clinical remission (919 patients, 63% with Crohn's disease) or endoscopic remission (290 patients, all with Crohn's disease). Median ustekinumab trough concentrations were higher amongst individuals achieving clinical remission compared with those not achieving remission (mean difference, 1.6 ug/mL; 95% confidence interval [CI], 0.21-3.01 ug/mL). Furthermore, individuals with median serum trough concentration in the fourth quartile were significantly more likely to achieve clinical (OR, 3.61; 95% CI, 2.11-6.20) but not endoscopic remission (OR, 4.67; 95% CI, 0.86-25.19) compared with those with first quartile median trough concentrations.
Based on the results of this meta-analysis primarily relating to patients with Crohn's disease on maintenance ustekinumab treatment, it appears that there is an association between higher ustekinumab trough concentration and clinical outcomes. Prospective studies are required to determine whether proactive dose adjustments of ustekinumab therapy provides additional clinical benefit.
优化治疗方案和监测应答反应是炎症性肠病治疗的重要组成部分。我们进行了一项系统回顾和荟萃分析，以确定维持治疗期间血清乌司奴单抗谷浓度与炎症性肠病患者乌司奴单抗治疗应答之间是否存在相关性。
系统回顾的检索时间截至 2022 年 3 月 21 日，检索数据库包括 MEDLINE、EMBASE 和 Cochrane 图书馆。我们纳入了报告血清乌司奴单抗谷浓度与临床或内镜缓解之间相关性的研究。使用二元结局的随机效应模型，对内镜和临床缓解的结局指标进行汇总。
我们共纳入 14 项观察性研究，用于分析临床缓解（919 例患者，63%患有克罗恩病）或内镜缓解（290 例患者，均患有克罗恩病）。与未缓解者相比，达到临床缓解者的乌司奴单抗谷浓度中位数更高（平均差值，1.6ug/mL；95%置信区间[CI]，0.21-3.01ug/mL）。此外，与血清谷浓度处于第一四分位数的患者相比，中位数处于第四四分位数的患者达到临床缓解（比值比[OR]，3.61；95%CI，2.11-6.20）的可能性显著更高，但达到内镜缓解（OR，4.67；95%CI，0.86-25.19）的可能性并无显著差异。
基于主要涉及维持乌司奴单抗治疗的克罗恩病患者的这项荟萃分析结果，乌司奴单抗谷浓度较高与临床结局似乎存在相关性。需要前瞻性研究来确定乌司奴单抗治疗的积极剂量调整是否能提供额外的临床获益。
