类风湿关节炎中肿瘤坏死因子抑制剂治疗的优化——一项原理验证和探索性试验：病情好转者逐渐减量用药是否可行？
Optimizing treatment with tumour necrosis factor inhibitors in rheumatoid arthritis-a proof of principle and exploratory trial: is dose tapering practical in good responders?
作者信息
Ibrahim Fowzia, Lorente-Cánovas Beatriz, Doré Caroline J, Bosworth Ailsa, Ma Margaret H, Galloway James B, Cope Andrew P, Pande Ira, Walker David, Scott David L
机构信息
Academic Department of Rheumatology, Division of Immunology, Infection and Inflammatory Disease, Faculty of Life Sciences and Medicine, King's College London.
Comprehensive Clinical Trials Unit, University College London, London.
出版信息
Rheumatology (Oxford). 2017 Nov 1;56(11):2004-2014. doi: 10.1093/rheumatology/kex315.
OBJECTIVES
RA patients receiving TNF inhibitors (TNFi) usually maintain their initial doses. The aim of the Optimizing Treatment with Tumour Necrosis Factor Inhibitors in Rheumatoid Arthritis trial was to evaluate whether tapering TNFi doses causes loss of clinical response.
METHODS
We enrolled RA patients receiving etanercept or adalimumab and a DMARD with DAS28 under 3.2 for over 3 months. Initially (months 0-6) patients were randomized to control (constant TNFi) or two experimental groups (tapering TNFi by 33 or 66%). Subsequently (months 6-12) control subjects were randomized to taper TNFi by 33 or 66%. Disease flares (DAS28 increasing ⩾0.6 with at least one additional swollen joint) were the primary outcome.
RESULTS
Two hundred and forty-four patients were screened, 103 randomized and 97 treated. In months 0-6 there were 8/50 (16%) flares in controls, 3/26 (12%) with 33% tapering and 6/21 (29%) with 66% tapering. Multivariate Cox analysis showed time to flare was unchanged with 33% tapering but was reduced with 66% tapering compared with controls (adjusted hazard ratio 2.81, 95% CI: 0.99, 7.94; P = 0.051). Analysing all tapered patients after controls were re-randomized (months 6-12) showed differences between groups: there were 6/48 (13%) flares with 33% tapering and 14/39 (36%) with 66% tapering. Multivariate Cox analysis showed 66% tapering reduced time to flare (adjusted hazard ratio 3.47, 95% CI: 1.26, 9.58; P = 0.016).
CONCLUSION
Tapering TNFi by 33% has no impact on disease flares and appears practical in patients in sustained remission and low disease activity states.
TRAIL REGISTRATION
EudraCT, https://www.clinicaltrialsregister.eu, 2010-020738-24; ISRCTN registry, https://www.isrctn.com, 28955701.
目的
接受肿瘤坏死因子抑制剂（TNFi）治疗的类风湿关节炎（RA）患者通常维持初始剂量。类风湿关节炎中肿瘤坏死因子抑制剂优化治疗试验的目的是评估逐渐减少TNFi剂量是否会导致临床反应丧失。
方法
我们纳入了接受依那西普或阿达木单抗以及一种病情活动度评分（DAS28）低于3.2且持续超过3个月的改善病情抗风湿药（DMARD）治疗的RA患者。最初（0至6个月），患者被随机分为对照组（TNFi剂量恒定）或两个试验组（TNFi剂量分别减少33%或66%）。随后（6至12个月），对照组患者被随机分为TNFi剂量减少33%或66%。疾病复发（DAS28升高≥0.6且至少有一个额外的肿胀关节）是主要结局。
结果
共筛选了244例患者，103例被随机分组，97例接受治疗。在0至6个月期间，对照组有8/50（16%）例复发，33%剂量递减组有3/26（12%）例复发，66%剂量递减组有6/21（29%）例复发。多因素Cox分析显示，与对照组相比，33%剂量递减时疾病复发时间无变化，但66%剂量递减时疾病复发时间缩短（调整后风险比2.81，95%置信区间：0.99，7.94；P = 0.051）。在对照组重新随机分组后（6至12个月）分析所有剂量递减的患者，结果显示组间存在差异：33%剂量递减组有6/48（13%）例复发，66%剂量递减组有14/39（36%）例复发。多因素Cox分析显示，66%剂量递减可缩短疾病复发时间（调整后风险比3.47，95%置信区间：1.26，9.58；P = 0.016）。
结论
TNFi剂量减少33%对疾病复发无影响，对于处于持续缓解和低疾病活动状态的患者似乎是可行的。
试验注册
欧洲临床试验数据库（EudraCT），https://www.clinicaltrialsregister.eu，2010 - 020738 - 24；国际标准随机对照试验编号注册库（ISRCTN registry），https://www.isrctn.com，28955701。
Zotero 插件