Department of Rheumatology, Copenhagen University Hospital at Køge, Lykkebækvej 1, DK-4600 Køge, Denmark; Department of Clinical Biochemistry, Copenhagen University Hospital at Køge, Lykkebækvej 1, DK-4600 Køge, Denmark; The Parker Institute, Department of Rheumatology, Copenhagen University Hospitals at Frederiksberg and Bispebjerg, DK-2000 Copenhagen F, Denmark.
Semin Arthritis Rheum. 2013 Oct;43(2):144-51. doi: 10.1016/j.semarthrit.2013.01.007. Epub 2013 Jul 6.
To summarize the empirical evidence regarding the effect of treatment intensification on clinical outcomes in patients with rheumatoid arthritis treated with one of the TNF-α-inhibitors, adalimumab, etanercept or infliximab.
A systematic search of the bibliographic databases Embase, Medline, Web of Science and Cochrane Central identifying articles concerning treatment with adalimumab, etanercept or infliximab in adult patients with rheumatoid arthritis exposed to dose increase or shortening of dosing intervals was performed. Longitudinal cohorts, both clinical trials and observational studies, were included. ACR and EULAR response criteria and DAS28 were the preferred outcome measures.
Out of 1135 records, eleven studies were included in the final evidence synthesis. One article concerned all the three TNF-α-inhibitors, eight used infliximab, one adalimumab and one etanercept. According to GRADE, evidence was weakened in particular by the lack of control groups, and for treatment intensification with adalimumab and etanercept, no conclusions could be drawn. With infliximab, two trials of high quality revealed contradictory results, but six studies described an improved clinical outcome following intensified treatment strategies. Some studies (2/2) also indicated that for infliximab, frequency increase was superior to dose increase.
Available studies indicate that intensifying treatment with infliximab in rheumatoid arthritis patients, preferably by increasing the frequency of drug administration, may lead to improved clinical outcome in some patients, but the evidence is weak. There is an urgent need for prospectively designed cohort studies to be able to draw a final conclusion.
总结关于在使用 TNF-α 抑制剂（阿达木单抗、依那西普或英夫利昔单抗）治疗类风湿关节炎患者中，强化治疗对临床结局影响的经验证据。
系统检索 Embase、Medline、Web of Science 和 Cochrane Central 数据库，查找关于在接受阿达木单抗、依那西普或英夫利昔单抗治疗的成年类风湿关节炎患者中增加剂量或缩短给药间隔的治疗的文章。纳入了纵向队列研究，包括临床试验和观察性研究。ACR 和 EULAR 缓解标准和 DAS28 是首选的结局测量指标。
在 1135 条记录中，有 11 项研究纳入了最终的证据综合分析。其中一篇文章涉及所有三种 TNF-α 抑制剂，8 项研究使用英夫利昔单抗，1 项研究使用阿达木单抗，1 项研究使用依那西普。根据 GRADE，证据特别因缺乏对照组而减弱，对于阿达木单抗和依那西普的强化治疗，无法得出结论。对于英夫利昔单抗，两项高质量的试验得出了相互矛盾的结果，但 6 项研究描述了强化治疗策略后临床结局的改善。一些研究（2/2）还表明，对于英夫利昔单抗，增加给药频率优于增加剂量。
现有研究表明，在类风湿关节炎患者中强化英夫利昔单抗治疗，最好通过增加药物给药频率，可能会改善一些患者的临床结局，但证据较弱。迫切需要前瞻性设计的队列研究来得出最终结论。
