Verhoef Lise M, Tweehuysen Lieke, Hulscher Marlies E, Fautrel Bruno, den Broeder Alfons A
Department of Rheumatology, Sint Maartenskliniek, Nijmegen, The Netherlands.
IQ Healthcare, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Rheumatol Ther. 2017 Jun;4(1):1-24. doi: 10.1007/s40744-017-0055-5. Epub 2017 Mar 2.
Although bDMARDs are effective in the treatment of RA, they are associated with dose-dependent side effects, patient burden, and high costs. Recently, many studies have investigated the possibility of discontinuing or tapering bDMARDs when patients have reached their treatment goal. The aim of this review is to provide a narrative overview of the existing evidence on bDMARD dose reduction and to provide answers to specific dose-reduction-related questions that are of interest to clinicians.
We systematically searched for relevant studies in four scientific databases. Furthermore, we screened the references of reviews and relevant studies.
Our searches resulted in 45 original studies of bDMARD dose reduction in RA patients (15 RCTs and 30 observational studies). Current evidence shows that bDMARD dose reduction can be considered in all RA patients who achieve stable (e.g., ≥6 months) low disease activity or remission. The best strategies seem to be disease-activity-guided dose optimization and fixed dose reduction, since direct bDMARD discontinuation (without restarting) results in a high flare rate, worse physical functioning, and more joint damage. When tapering the bDMARD treatment of a patient, disease activity should be monitored closely, and if a flare occurs, the dose should be increased to the lowest effective dose. Current evidence shows that restarting bDMARD treatment is effective and safe. Unfortunately, no clear predictors of successful dose reduction have been identified so far.
The current evidence and rising healthcare costs urge that dose reduction should be considered for eligible patients. However, the decision to start dose reduction should be made in shared decision-making. Future research should focus not only on a better understanding of the effects of dose reduction on clinical outcomes but also on the perspectives of patients and physicians as well as the implementation of this new treatment principle.
尽管生物性改善病情抗风湿药（bDMARDs）在类风湿关节炎（RA）治疗中有效，但它们与剂量依赖性副作用、患者负担及高成本相关。近来，许多研究探讨了患者达到治疗目标时停用或减停bDMARDs的可能性。本综述旨在对bDMARDs剂量降低的现有证据进行叙述性概述，并回答临床医生感兴趣的与剂量降低相关的具体问题。
我们在四个科学数据库中系统检索相关研究。此外，我们筛选了综述及相关研究的参考文献。
我们的检索得到45项关于RA患者bDMARDs剂量降低的原始研究（15项随机对照试验和30项观察性研究）。目前的证据表明，所有达到稳定（如≥6个月）低疾病活动度或缓解的RA患者都可考虑降低bDMARDs剂量。最佳策略似乎是疾病活动度引导的剂量优化和固定剂量降低，因为直接停用bDMARDs（不再重新开始）会导致高复发率、更差的身体功能及更多的关节损伤。在逐渐减少患者的bDMARDs治疗时，应密切监测疾病活动度，若出现复发，剂量应增加至最低有效剂量。目前的证据表明重新开始bDMARDs治疗是有效且安全的。遗憾的是，目前尚未明确成功降低剂量的预测因素。
当前的证据及不断上升的医疗成本促使应考虑对符合条件的患者进行剂量降低。然而，开始剂量降低的决定应通过共同决策做出。未来的研究不仅应聚焦于更好地理解剂量降低对临床结局的影响，还应关注患者和医生的观点以及这一新治疗原则的实施。
