比较甲氨蝶呤单药治疗与甲氨蝶呤联合来氟米特治疗银屑病关节炎：一项随机、安慰剂对照、双盲临床试验方案（COMPLETE-PsA）。

Comparing methotrexate monotherapy with methotrexate plus leflunomide combination therapy in psoriatic arthritis: protocol of a randomized, placebo-controlled, double-blind clinical trial (COMPLETE-PsA).

机构信息

Department of Rheumatology, Sint Maartenskliniek, PO Box 9011, Nijmegen, 6500 GM, The Netherlands.

Department of Rheumatic Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.

出版信息

Trials. 2020 Feb 10;21(1):155. doi: 10.1186/s13063-020-4097-6.

DOI:10.1186/s13063-020-4097-6

PMID:32041657

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7011519/

Abstract

BACKGROUND

Both methotrexate (MTX) and leflunomide (LEF) are registered and regularly prescribed as first-line treatments for the use in patients with psoriatic arthritis (PsA) and they are occasionally used in combination. However, evidence about their individual, and especially combined efficacy, in PsA is lacking. The aim of this study is to compare the effectiveness and safety of MTX and LEF combination therapy to MTX monotherapy in patients with PsA.

METHODS

COMPLETE-PsA is a randomized, placebo-controlled, double-blind clinical trial. Disease-modifying antirheumatic drug (DMARD)-untreated patients (n = 78) with clinical diagnosis of active (i.e. ≥2 swollen joints) PsA will be randomized 1:1 (stratified for high disease activity, Psoriatic Arthritis Disease Activity Score [PASDAS] ≥ 5.4) to the combination or monotherapy. The intervention group receives MTX 25 mg (oral or subcutaneous) once weekly plus LEF 20 mg daily, and the control group receives the same but with placebo instead of LEF daily. Primary endpoint is between-group difference in PASDAS at 16 weeks, adjusted for baseline PASDAS. Key secondary parameters include between-group comparisons in change in Disease Activity in Psoriatic Arthritis (DAPSA) score, skin score, enthesitis score, dactylitis score, and swollen/tender joint count, as well as the proportion of patients fulfilling minimal disease activity (MDA), American College of Rheumatology (ACR) 20/50/70 response criteria at week 16. Furthermore, safety, function and quality of life (Health Assessment Questionnaire [HAQ], Psoriatic Arthritic Impact of Disease [PSAID], Short Form 12 [SF-12]) will be assessed.

DISCUSSION

This is, to our knowledge, the first randomized, placebo-controlled, double-blind clinical trial assessing the effectiveness of MTX and LEF combination therapy in patients with PsA. The study will provide important information for treatment strategies and treatment recommendations.

TRIAL REGISTRATION

Dutch Trial Register NTR7632 (3 December 2018). CMO NL66544.091.18 (19 November 2018).

摘要

背景

甲氨蝶呤（MTX）和来氟米特（LEF）均为注册药物，且通常被开为治疗银屑病关节炎（PsA）的一线药物，且有时会联合使用。然而，关于它们在 PsA 中的单独使用，尤其是联合使用的疗效证据尚缺乏。本研究旨在比较 MTX 和 LEF 联合治疗与 MTX 单药治疗在 PsA 患者中的有效性和安全性。

方法

COMPLETE-PsA 是一项随机、安慰剂对照、双盲临床试验。将 78 例临床诊断为活动期（即≥2 个肿胀关节）银屑病关节炎、未接受过疾病修饰抗风湿药物（DMARD）治疗的患者（n=78）按 1:1（根据高疾病活动度分层，银屑病关节炎疾病活动评分[PASDAS]≥5.4）随机分为联合组或单药组。联合组给予 MTX 25mg（口服或皮下）每周一次，加 LEF 20mg 每日一次；对照组给予相同药物，但每日给予安慰剂代替 LEF。主要终点为治疗 16 周时，两组间 PASDAS 的差值，根据基线 PASDAS 进行调整。关键次要参数包括两组间 DAPSA 评分、皮肤评分、附着点炎评分、指炎评分、肿胀/触痛关节计数的变化比较，以及 16 周时达到最小疾病活动度（MDA）、美国风湿病学会（ACR）20/50/70 缓解标准的患者比例。此外，安全性、功能和生活质量（健康评估问卷[HAQ]、银屑病关节炎对疾病的影响[PSAID]、短表 12[SF-12]）也将进行评估。