Abstract：
BACKGROUND: The long-term use of anti-TNF-α agents can lead to adverse effects, such as infections and immune-mediated cutaneous reactions. Whether de-escalation by dose reduction or interval lengthening reduces these adverse effects is uncertain. This systematic review aims to compare the incidence of infections and skin manifestations after anti-TNF-α dose de-escalation with standard dosing.
METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception to 14 January 2022. Randomized controlled trials (RCTs) and observational studies comparing anti-TNF-α de-escalation strategies with standard dosing among patients with inflammatory conditions, that report on infections, skin manifestations, or both, were included. The risk of bias was assessed with the revised Cochrane risk-of bias tool (RCTs) or the Newcastle-Ottawa scale (non-RCTs).
RESULTS: Fourteen RCTs and six observational studies (or 2706 patients) were included. Eight RCTs had low risk of bias or some concerns. Four non-RCTs were of good methodological quality. The studies described patients with axial spondyloarthritis (8 studies, 780 patients), rheumatoid arthritis (7 studies, 1458 patients), psoriasis (3 studies, 332 patients), or inflammatory bowel disease (2 studies, 136 patients). De-escalation strategies included interval lengthening (12 studies, 1317 patients), dose reduction (6 studies, 1130 patients), or both (2 studies, 259 patients). Overall, the occurrence of infections and skin manifestations did not differ between standard treatment and de-escalation. The disappearance of infections or skin manifestations after de-escalation was only reported in two studies. The majority of studies focused on etanercept and adalimumab. Heterogeneity in reporting of infections and skin manifestations precluded meta-analysis.
CONCLUSIONS: We found that anti-TNF-α de-escalation does not reduce infections or skin reactions. A de-escalation strategy should not be recommended for the sole purpose of reducing drug-related adverse effects. The meticulous documentation of adverse effects is recommended to further address this question.
BACKGROUND: PROSPERO CRD42021252977.
METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception to 14 January 2022. Randomized controlled trials (RCTs) and observational studies comparing anti-TNF-α de-escalation strategies with standard dosing among patients with inflammatory conditions, that report on infections, skin manifestations, or both, were included. The risk of bias was assessed with the revised Cochrane risk-of bias tool (RCTs) or the Newcastle-Ottawa scale (non-RCTs).
RESULTS: Fourteen RCTs and six observational studies (or 2706 patients) were included. Eight RCTs had low risk of bias or some concerns. Four non-RCTs were of good methodological quality. The studies described patients with axial spondyloarthritis (8 studies, 780 patients), rheumatoid arthritis (7 studies, 1458 patients), psoriasis (3 studies, 332 patients), or inflammatory bowel disease (2 studies, 136 patients). De-escalation strategies included interval lengthening (12 studies, 1317 patients), dose reduction (6 studies, 1130 patients), or both (2 studies, 259 patients). Overall, the occurrence of infections and skin manifestations did not differ between standard treatment and de-escalation. The disappearance of infections or skin manifestations after de-escalation was only reported in two studies. The majority of studies focused on etanercept and adalimumab. Heterogeneity in reporting of infections and skin manifestations precluded meta-analysis.
CONCLUSIONS: We found that anti-TNF-α de-escalation does not reduce infections or skin reactions. A de-escalation strategy should not be recommended for the sole purpose of reducing drug-related adverse effects. The meticulous documentation of adverse effects is recommended to further address this question.
BACKGROUND: PROSPERO CRD42021252977.
摘要：
背景：长期使用抗TNF-α药物会导致不良反应，如感染和免疫介导的皮肤反应。通过剂量减少或间隔时间延长来降低这些不良反应是不确定的。本系统评价旨在比较抗TNF-α剂量降低与标准剂量后感染的发生率和皮肤表现。
方法：MEDLINE，EMBASE,从开始到2022年1月14日，搜索了Cochrane中央控制试验登记册。随机对照试验（RCTs）和观察性研究，比较抗TNF-α降低策略与标准剂量在炎症患者中，报告感染，皮肤表现，或者两者兼而有之,包括在内。使用修订后的Cochrane偏差风险工具（RCT）或纽卡斯尔-渥太华量表（非RCT）评估偏差风险。
结果：纳入了14项随机对照试验和6项观察性研究（或2706名患者）。八个随机对照试验的偏倚或一些担忧风险较低。四个非随机对照试验具有良好的方法学质量。研究描述了轴性脊柱关节炎患者(8项研究，780名患者），类风湿性关节炎（7项研究，1458名患者），牛皮癣（3项研究，332名患者），或炎症性肠病（2项研究，136名患者)。降级策略包括间隔时间延长(12项研究，1317名患者），剂量减少(6项研究，1130名患者），或两者(2项研究，259名患者）。总的来说,在标准治疗和降阶梯治疗之间,感染的发生和皮肤表现没有差异.仅在两项研究中报告了降级后感染或皮肤表现的消失。大多数研究集中在依那西普和阿达木单抗上。报告感染和皮肤表现的异质性排除了荟萃分析。
结论：我们发现，抗TNF-α降阶梯并不能减少感染或皮肤反应。不应仅出于减少药物相关不良反应的目的而建议采取降级策略。建议对不良反应进行细致的记录，以进一步解决这一问题。
背景：PROSPEROCRD42021252977.
方法：MEDLINE，EMBASE,从开始到2022年1月14日，搜索了Cochrane中央控制试验登记册。随机对照试验（RCTs）和观察性研究，比较抗TNF-α降低策略与标准剂量在炎症患者中，报告感染，皮肤表现，或者两者兼而有之,包括在内。使用修订后的Cochrane偏差风险工具（RCT）或纽卡斯尔-渥太华量表（非RCT）评估偏差风险。
结果：纳入了14项随机对照试验和6项观察性研究（或2706名患者）。八个随机对照试验的偏倚或一些担忧风险较低。四个非随机对照试验具有良好的方法学质量。研究描述了轴性脊柱关节炎患者(8项研究，780名患者），类风湿性关节炎（7项研究，1458名患者），牛皮癣（3项研究，332名患者），或炎症性肠病（2项研究，136名患者)。降级策略包括间隔时间延长(12项研究，1317名患者），剂量减少(6项研究，1130名患者），或两者(2项研究，259名患者）。总的来说,在标准治疗和降阶梯治疗之间,感染的发生和皮肤表现没有差异.仅在两项研究中报告了降级后感染或皮肤表现的消失。大多数研究集中在依那西普和阿达木单抗上。报告感染和皮肤表现的异质性排除了荟萃分析。
结论：我们发现，抗TNF-α降阶梯并不能减少感染或皮肤反应。不应仅出于减少药物相关不良反应的目的而建议采取降级策略。建议对不良反应进行细致的记录，以进一步解决这一问题。
背景：PROSPEROCRD42021252977.
