羟氯喹、柳氮磺胺吡啶、甲氨蝶呤三联疗法预防类风湿关节炎达到临床缓解或低疾病活动度患者复发的疗效、安全性和成本效益：一项随机对照临床试验（ESCoRT 研究）方案。
The efficacy, safety and cost-effectiveness of hydroxychloroquine, sulfasalazine, methotrexate triple therapy in preventing relapse among patients with rheumatoid arthritis achieving clinical remission or low disease activity: the study protocol of a randomized controlled clinical Trial (ESCoRT study).
机构信息
Department of Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing, 100034, China.
Peking University Clinical Research Institute (PUCRI), Beijing, 100083, China.
出版信息
BMC Med Inform Decis Mak. 2021 Mar 4;21(1):83. doi: 10.1186/s12911-021-01449-2.
BACKGROUND
Tumor necrosis factor α inhibitors (TNFi) is effective for rheumatoid arthritis (RA) patients who fail to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Because of high cost, the discontinuation is common but often lead to disease relapse. The study aims to investigate, if the combination therapy of csDMARDs is more effective in reducing disease relapse than methotrexate (MTX) monotherapy, and more cost-effective than continuing TNFi and MTX.
METHODS
It will be a two-stage trial. In the first stage, all RA patients who failed to csDMARDs treatment [disease activity score 28 (DAS28)-CRP > 3.2] will receive MTX plus TNFi for no more than 12 weeks. Patients achieving DAS28-CRP < 3.2 during the first stage will be randomized into three groups at 1:1:1 ratio: (A) add hydroxychloroquine (HCQ) and sulfasalazine (SSZ) for the first 12 weeks and then remove TNFi but continue other treatments for the next 48 weeks; (B) maintain TNFi + MTX for 60 weeks; and (C) maintain TNFi + MTX for the first 12 weeks and then remove TNFi but continue MTX monotherapy for the next 48 weeks. The primary outcome will be disease relapse (DAS28-CRP increases by at least 0.6 and > 3.2). Secondary outcomes will include the incremental cost per reducing 1 case of relapse; patient reported intolerance to the treatment; adverse events; change of mean disease activity measured by DAS28, clinical disease activity index (CDAI) and simplified disease activity index (SDAI); the proportion of modified Sharp score increase < 0.3; ultrasound-detected remission in hands; Health Assessment Questionnaire Disability Index (HAQ-DI) and health related quality of life [the five-level EuroQol-5D (EQ-5D-5L) and short form-6D (SF-6D)].
DISCUSSION
The aim of this trail will be to seek effective treatment options of preventing relapse of RA. The results of the current study may provide an instructive recommendation for more economical application of TNFi treatment in RA. Trial registration NCT, NCT02320630. Registered on 16 December 2014. https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=3&cx=-jg9qo2 .
背景
肿瘤坏死因子 α 抑制剂（TNFi）对未能接受传统合成改善病情抗风湿药物（csDMARDs）治疗的类风湿关节炎（RA）患者有效。由于费用高昂，停药很常见，但往往会导致疾病复发。本研究旨在探讨 csDMARDs 联合治疗是否比甲氨蝶呤（MTX）单药治疗更能降低疾病复发率，以及是否比继续使用 TNFi 和 MTX 更具成本效益。
方法
这将是一项两阶段试验。在第一阶段，所有未能接受 csDMARDs 治疗的 RA 患者[疾病活动评分 28（DAS28）-C 反应蛋白（CRP）>3.2]将接受 MTX 加 TNFi 治疗，不超过 12 周。在第一阶段达到 DAS28-CRP<3.2 的患者将以 1:1:1 的比例随机分为三组：（A）在前 12 周添加羟氯喹（HCQ）和柳氮磺胺吡啶（SSZ），然后去除 TNFi，但继续下一 48 周的其他治疗；（B）维持 TNFi+MTX 治疗 60 周；（C）维持 TNFi+MTX 治疗 12 周，然后去除 TNFi，但继续下一 48 周的 MTX 单药治疗。主要结局为疾病复发（DAS28-CRP 至少增加 0.6 且>3.2）。次要结局包括减少 1 例复发的成本增量；患者对治疗的不耐受；不良事件；用 DAS28、临床疾病活动指数（CDAI）和简化疾病活动指数（SDAI）测量的平均疾病活动的变化；改良 Sharp 评分增加<0.3 的比例；手部超声检测缓解；健康评估问卷残疾指数（HAQ-DI）和健康相关生活质量[五级欧洲五维健康量表（EQ-5D-5L）和六维度健康量表短表（SF-6D）]。
讨论
本试验的目的是寻求预防 RA 复发的有效治疗选择。本研究的结果可能为 TNFi 治疗在 RA 中的更经济应用提供有益的建议。试验注册 NCT，NCT02320630。于 2014 年 12 月 16 日注册。[https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=3&cx=-jg9qo2]。
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