Abstract：
The benefits of TDM-guided TNFi therapy in patients with rheumatic disease was still controversial. This systematic review and meta-analysis was conducted to explore if the TDM-guided TNFi therapy is superior to empirical-guided therapy.
We systematically searched PubMed, Web of Science, Cochrane Library, and EMBASE databases for articles published between database inception and October 05, 2023. Studies reporting endpoints in TDM-guided TNFi therapy and empirical therapy were included. Results would be presented in risk ratio (RR) and mean difference, with 95 % confidence interval (CI) reported. This study is registered with PROSPERO (CRD42022353956).
A total of 14 studies (eight RCTs and six cohort studies) involving 2427 patients were included in this meta-analysis. In the scenario of response prediction, compared with empirical-guided therapy, TDM-guided TNFi therapy had association with higher treat-to-target rates (RR 1.30, 95 % CI 1.02-1.65, P=0.03, I2=79 %), more specifically, higher low disease activity rates (RR 2.11, 95 % CI 1.22-3.66, P=0.007, I2=61 %), but no difference in clinical remission rates (RR 0.98,95 % CI 0.87-1.11, P=0.75, I2=0 %). In the scenario of dose reduction prediction, lower relapse rates (RR 0.73, 95 % CI 0.65-0.82, P <0.00001, I2=0 %) were observed compared with empirical-guided dose reduction strategy, but no difference (RR 1.24, 95 % CI 0.85-1.80, P=0.27, I2=57 %) between TDM-guided dose reduction and standard-dosing therapy. No significant difference was observed in change of disease activity score, mean disease activity score, radiographic progression, and safety. And TDM-guided therapy was associated with reduced cost per patient per year calculated as the total accumulated sum of therapy cost.
TDM-guided TNFi therapy was associated with increased rates of low disease activity and decreased risks of relapse, and may save cost compared with empirical-guided therapy in patients with rheumatic disease. But this does not mean that the use of TDM-guided TNFi therapy can be advocated, because there is no difference in clinical remission rates and many other outcomes. More researches, especially randomized clinical trials are needed to verify this conclusion in the future.
We systematically searched PubMed, Web of Science, Cochrane Library, and EMBASE databases for articles published between database inception and October 05, 2023. Studies reporting endpoints in TDM-guided TNFi therapy and empirical therapy were included. Results would be presented in risk ratio (RR) and mean difference, with 95 % confidence interval (CI) reported. This study is registered with PROSPERO (CRD42022353956).
A total of 14 studies (eight RCTs and six cohort studies) involving 2427 patients were included in this meta-analysis. In the scenario of response prediction, compared with empirical-guided therapy, TDM-guided TNFi therapy had association with higher treat-to-target rates (RR 1.30, 95 % CI 1.02-1.65, P=0.03, I2=79 %), more specifically, higher low disease activity rates (RR 2.11, 95 % CI 1.22-3.66, P=0.007, I2=61 %), but no difference in clinical remission rates (RR 0.98,95 % CI 0.87-1.11, P=0.75, I2=0 %). In the scenario of dose reduction prediction, lower relapse rates (RR 0.73, 95 % CI 0.65-0.82, P <0.00001, I2=0 %) were observed compared with empirical-guided dose reduction strategy, but no difference (RR 1.24, 95 % CI 0.85-1.80, P=0.27, I2=57 %) between TDM-guided dose reduction and standard-dosing therapy. No significant difference was observed in change of disease activity score, mean disease activity score, radiographic progression, and safety. And TDM-guided therapy was associated with reduced cost per patient per year calculated as the total accumulated sum of therapy cost.
TDM-guided TNFi therapy was associated with increased rates of low disease activity and decreased risks of relapse, and may save cost compared with empirical-guided therapy in patients with rheumatic disease. But this does not mean that the use of TDM-guided TNFi therapy can be advocated, because there is no difference in clinical remission rates and many other outcomes. More researches, especially randomized clinical trials are needed to verify this conclusion in the future.
摘要：
目的：TDM引导的TNFi治疗风湿性疾病患者的益处仍存在争议。进行了系统评价和荟萃分析，以探讨TDM指导的TNFi治疗是否优于经验指导的治疗。
方法：我们系统地搜索了PubMed，WebofScience,科克伦图书馆,和EMBASE数据库，用于在数据库开始到2023年10月5日之间发表的文章。包括报告TDM指导的TNFi治疗和经验性治疗终点的研究。结果将以风险比(RR)和平均差表示，报告95%置信区间(CI)。本研究在PROSPERO(CRD42022353956)注册。
结果：共有14项研究（8项随机对照试验和6项队列研究）纳入本荟萃分析，涉及2427例患者。在响应预测的场景中，与经验指导疗法相比，TDM引导的TNFi治疗与更高的治疗至目标率相关（RR1.30，95％CI1.02-1.65，P=0.03，I2=79％），更具体地说,较高的低疾病活动率（RR2.11，95％CI1.22-3.66，P=0.007，I2=61％），但临床缓解率无差异(RR0.98,95%CI0.87-1.11,P=0.75,I2=0%)。在剂量减少预测的情况下，与经验指导剂量减少策略相比，观察到较低的复发率（RR0.73，95％CI0.65-0.82，P<0.00001，I2=0％），但TDM引导剂量减少和标准剂量治疗之间没有差异(RR1.24,95%CI0.85-1.80,P=0.27,I2=57%).疾病活动性评分变化无显著差异，平均疾病活动评分，放射学进展，和安全。TDM指导的治疗与每位患者每年的成本降低相关，计算为治疗成本的总累积总和。
结论：TDM引导的TNFi治疗与低疾病活动度和复发风险降低相关，与风湿性疾病患者的经验指导治疗相比，可以节省成本。但这并不意味着可以提倡使用TDM引导的TNFi治疗，因为临床缓解率和许多其他结局没有差异。更多研究,特别是随机临床试验需要验证这一结论。
方法：我们系统地搜索了PubMed，WebofScience,科克伦图书馆,和EMBASE数据库，用于在数据库开始到2023年10月5日之间发表的文章。包括报告TDM指导的TNFi治疗和经验性治疗终点的研究。结果将以风险比(RR)和平均差表示，报告95%置信区间(CI)。本研究在PROSPERO(CRD42022353956)注册。
结果：共有14项研究（8项随机对照试验和6项队列研究）纳入本荟萃分析，涉及2427例患者。在响应预测的场景中，与经验指导疗法相比，TDM引导的TNFi治疗与更高的治疗至目标率相关（RR1.30，95％CI1.02-1.65，P=0.03，I2=79％），更具体地说,较高的低疾病活动率（RR2.11，95％CI1.22-3.66，P=0.007，I2=61％），但临床缓解率无差异(RR0.98,95%CI0.87-1.11,P=0.75,I2=0%)。在剂量减少预测的情况下，与经验指导剂量减少策略相比，观察到较低的复发率（RR0.73，95％CI0.65-0.82，P<0.00001，I2=0％），但TDM引导剂量减少和标准剂量治疗之间没有差异(RR1.24,95%CI0.85-1.80,P=0.27,I2=57%).疾病活动性评分变化无显著差异，平均疾病活动评分，放射学进展，和安全。TDM指导的治疗与每位患者每年的成本降低相关，计算为治疗成本的总累积总和。
结论：TDM引导的TNFi治疗与低疾病活动度和复发风险降低相关，与风湿性疾病患者的经验指导治疗相比，可以节省成本。但这并不意味着可以提倡使用TDM引导的TNFi治疗，因为临床缓解率和许多其他结局没有差异。更多研究,特别是随机临床试验需要验证这一结论。
