PDF(Pubmed)
Abstract：
UNASSIGNED: Persistent uncertainties exist surrounding the therapeutic drug monitoring (TDM) of adalimumab in clinical settings. To address these issues, we conducted a systematic review to assess the current evidence regarding the benefits of TDM for adalimumab.
UNASSIGNED: PubMed, EMBASE, and Cochrane Databases were searched from inception to October 2022. The trials regarding to the list three key questions were considered: 1) Could routine proactive TDM assist in improving outcomes in patients receiving adalimumab? 2) Could reactive TDM assist in guiding subsequent treatment strategies for patients with treatment failure to adalimumab? 3) Could TDM assist in informing dose reduction or discontinuation in patients with low disease activity or in remission treated with adalimumab? Two reviewers independently selected the studies and extracted the data. Meta-analysis was performed to calculate the relative risk (RR) and 95% confidence interval (CI).
UNASSIGNED: A total of 9 studies was included in this review. For proactive TDM, meta-analysis indicated that proactive TDM (n = 163/257, 63.42%) showed no significant superiority over reactive TDM and/or conventional management (n = 336/606, 55.44%) in achieving and/or maintaining clinical remission by random effects model (RR: 1.24, 95% CI 0.98-1.58, I 2 = 73%). There were three studies that supporting the reactive TDM, low drug levels in the absence of anti-drug antibodies (ADA) strongly indicate the need for dose intensification, and infliximab is a feasible choice for patients with low drug levels and ADA positivity. While swapping to another class should be considered in patients with adequate drug levels. In addition, TDM can help clinicians optimize dosing schedules and prevent overtreatment in patients who have achieved low disease activity and sufficient drug concentrations, with no predictive value for successful adalimumab discontinuation.
UNASSIGNED: Current evidence suggests that proactive TDM is numerically but not statistically significant superiority over reactive TDM and/or conventional management. Reactive TDM can aid in understanding treatment failure and developing subsequent therapy. For patients reaching low disease activity and remission, TDM can help successful dose reduction, while it cannot inform the successful drug discontinuation. However, existing trials are limited, and more well-designed trials are necessary to clarify the role of TDM in adalimumab treatment.
UNASSIGNED: PubMed, EMBASE, and Cochrane Databases were searched from inception to October 2022. The trials regarding to the list three key questions were considered: 1) Could routine proactive TDM assist in improving outcomes in patients receiving adalimumab? 2) Could reactive TDM assist in guiding subsequent treatment strategies for patients with treatment failure to adalimumab? 3) Could TDM assist in informing dose reduction or discontinuation in patients with low disease activity or in remission treated with adalimumab? Two reviewers independently selected the studies and extracted the data. Meta-analysis was performed to calculate the relative risk (RR) and 95% confidence interval (CI).
UNASSIGNED: A total of 9 studies was included in this review. For proactive TDM, meta-analysis indicated that proactive TDM (n = 163/257, 63.42%) showed no significant superiority over reactive TDM and/or conventional management (n = 336/606, 55.44%) in achieving and/or maintaining clinical remission by random effects model (RR: 1.24, 95% CI 0.98-1.58, I 2 = 73%). There were three studies that supporting the reactive TDM, low drug levels in the absence of anti-drug antibodies (ADA) strongly indicate the need for dose intensification, and infliximab is a feasible choice for patients with low drug levels and ADA positivity. While swapping to another class should be considered in patients with adequate drug levels. In addition, TDM can help clinicians optimize dosing schedules and prevent overtreatment in patients who have achieved low disease activity and sufficient drug concentrations, with no predictive value for successful adalimumab discontinuation.
UNASSIGNED: Current evidence suggests that proactive TDM is numerically but not statistically significant superiority over reactive TDM and/or conventional management. Reactive TDM can aid in understanding treatment failure and developing subsequent therapy. For patients reaching low disease activity and remission, TDM can help successful dose reduction, while it cannot inform the successful drug discontinuation. However, existing trials are limited, and more well-designed trials are necessary to clarify the role of TDM in adalimumab treatment.
摘要：
■临床环境中围绕阿达木单抗的治疗药物监测(TDM)存在持续的不确定性。为了解决这些问题,我们进行了系统评价,以评估目前关于TDM对阿达木单抗的益处的证据.
■PubMed,EMBASE,和Cochrane数据库从开始到2022年10月进行了搜索。考虑了有关列表三个关键问题的试验：1）常规的主动TDM是否可以帮助改善接受阿达木单抗的患者的预后？2）反应性TDM是否可以帮助指导阿达木单抗治疗失败的患者的后续治疗策略？3）TDM是否可以帮助告知疾病活动度低或接受阿达木单抗治疗缓解的患者的剂量减少或停药？两名评审员独立选择了研究并提取了数据。采用Meta分析计算相对危险度(RR)和95%置信区间(CI)。
■本综述共纳入9项研究。对于主动TDM，荟萃分析显示，通过随机效应模型（RR：1.24，95％CI0.98-1.58，I2=73％），主动TDM（n=163/257，63.42％）在实现和/或维持临床缓解方面没有明显优于反应性TDM和/或常规治疗（n=336/606，55.44％）。有三项研究支持反应性TDM，在没有抗药物抗体（ADA）的情况下，低药物水平强烈表明需要加强剂量，对于药物水平低且ADA阳性的患者,英夫利昔单抗是可行的选择.在具有足够药物水平的患者中，应考虑交换到另一类。此外,TDM可以帮助临床医生优化给药方案，防止疾病活动度低和药物浓度充足的患者过度治疗。对阿达木单抗成功停药没有预测价值。
■目前的证据表明，与反应性TDM和/或常规管理相比，主动TDM在数值上但没有统计学上的显著优势。反应性TDM可以帮助理解治疗失败和发展后续治疗。对于疾病活动度低和缓解的患者，TDM可以帮助成功减少剂量，虽然它不能通知成功停药。然而,现有的试验是有限的，需要更精心设计的试验来阐明TDM在阿达木单抗治疗中的作用.
■PubMed,EMBASE,和Cochrane数据库从开始到2022年10月进行了搜索。考虑了有关列表三个关键问题的试验：1）常规的主动TDM是否可以帮助改善接受阿达木单抗的患者的预后？2）反应性TDM是否可以帮助指导阿达木单抗治疗失败的患者的后续治疗策略？3）TDM是否可以帮助告知疾病活动度低或接受阿达木单抗治疗缓解的患者的剂量减少或停药？两名评审员独立选择了研究并提取了数据。采用Meta分析计算相对危险度(RR)和95%置信区间(CI)。
■本综述共纳入9项研究。对于主动TDM，荟萃分析显示，通过随机效应模型（RR：1.24，95％CI0.98-1.58，I2=73％），主动TDM（n=163/257，63.42％）在实现和/或维持临床缓解方面没有明显优于反应性TDM和/或常规治疗（n=336/606，55.44％）。有三项研究支持反应性TDM，在没有抗药物抗体（ADA）的情况下，低药物水平强烈表明需要加强剂量，对于药物水平低且ADA阳性的患者,英夫利昔单抗是可行的选择.在具有足够药物水平的患者中，应考虑交换到另一类。此外,TDM可以帮助临床医生优化给药方案，防止疾病活动度低和药物浓度充足的患者过度治疗。对阿达木单抗成功停药没有预测价值。
■目前的证据表明，与反应性TDM和/或常规管理相比，主动TDM在数值上但没有统计学上的显著优势。反应性TDM可以帮助理解治疗失败和发展后续治疗。对于疾病活动度低和缓解的患者，TDM可以帮助成功减少剂量，虽然它不能通知成功停药。然而,现有的试验是有限的，需要更精心设计的试验来阐明TDM在阿达木单抗治疗中的作用.
