Hartman Linda, Rasch Linda A, Klausch Thomas, Bijlsma Hans W J, Christensen Robin, Smulders Yvo M, Ralston Stuart H, Buttgereit Frank, Cutolo Maurizio, Da Silva Jose A P, Opris Daniela, Rovenský Jozef, Szamosi Szilvia, Middelink Leonie M, Lems Willem F, Boers Maarten
Amsterdam Rheumatology and Immunology Center ARC, VU University Medical Center, Amsterdam, The Netherlands.
Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
Trials. 2018 Jan 25;19(1):67. doi: 10.1186/s13063-017-2396-3.
Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints affecting 1% of the world population. It has major impact on patients through disability and associated comorbidities. Current treatment strategies have considerably improved the prognosis, but recent innovations (especially biologic drugs and the new class of so-called "JAK/STAT inhibitors") have important safety issues and are very costly. Glucocorticoids (GCs) are highly effective in RA, and could reduce the need for expensive treatment with biologic agents. However, despite more than 65 years of clinical experience, there is a lack of studies large enough to adequately document the benefit/harm balance. The result is inappropriate treatment strategies, i.e. both under-use and over-use of GCs, and consequently suboptimal treatment of RA.
The GLORIA study is a pragmatic multicentre, 2-year, randomised, double-blind, clinical trial to assess the safety and effectiveness of a daily dose of 5 mg prednisolone or matching placebo added to standard of care in elderly patients with RA. Eligible participants are diagnosed with RA, have inadequate disease control (disease activity score, DAS28 ≥ 2.6), and are ≥ 65 years. The primary outcome measures are the time-averaged mean value of the DAS28 and the occurrence of serious adverse events or adverse events of special interest. During the trial, change in antirheumatic therapy is permitted as clinically indicated, except for GCs. Cost-effectiveness and cost-utility are secondary outcomes. The main challenge is the interpretation of the trial result with two primary endpoints and the pragmatic trial design that allows co-interventions. Another challenge is the definition of safety and the relative lack of power to detect differences between treatment groups. We have chosen to define safety as the number of patients experiencing at least one serious adverse event. We also specify a decision tree to guide our conclusion on the balance of benefit and harm, and our methodology to combat potential confounding caused by co-interventions.
Pragmatic trials minimise impact on daily practice and maximise clinical relevance of the results, but analysis and interpretation of the results is challenging. We expect that the results of this trial are of importance for all rheumatologists who treat elderly patients with RA.
ClinicalTrials.gov, NCT02585258 . Registered on 20 October 2015.
类风湿关节炎（RA）是一种影响全球1%人口的慢性关节炎症性疾病。它通过导致残疾和相关合并症对患者产生重大影响。目前的治疗策略已显著改善了预后，但近期的创新疗法（尤其是生物药物和新一类所谓的“JAK/STAT抑制剂”）存在重要的安全问题且成本高昂。糖皮质激素（GCs）在类风湿关节炎治疗中疗效显著，可减少使用昂贵生物制剂治疗的需求。然而，尽管有超过65年的临床经验，但仍缺乏足够大的研究来充分记录其利弊平衡。结果导致治疗策略不当，即糖皮质激素的使用不足和过度使用，进而使类风湿关节炎的治疗效果欠佳。
GLORIA研究是一项务实的多中心、为期2年的随机双盲临床试验，旨在评估每日剂量5毫克泼尼松龙或匹配安慰剂添加到老年类风湿关节炎患者标准治疗中的安全性和有效性。符合条件的参与者被诊断为类风湿关节炎，疾病控制不佳（疾病活动评分，DAS28≥2.6），且年龄≥65岁。主要结局指标是DAS28的时间平均均值以及严重不良事件或特殊关注不良事件的发生情况。在试验期间，除糖皮质激素外，可根据临床指征允许改变抗风湿治疗。成本效益和成本效用是次要结局。主要挑战在于对具有两个主要终点的试验结果进行解读以及允许联合干预的务实试验设计。另一个挑战是安全性的定义以及检测治疗组间差异的相对效能不足。我们选择将安全性定义为经历至少一次严重不良事件的患者数量。我们还指定了一个决策树来指导我们对利弊平衡的结论以及应对联合干预导致的潜在混杂因素的方法。
务实试验将对日常实践的影响降至最低，并使结果的临床相关性最大化，但结果的分析和解读具有挑战性。我们预计该试验结果对所有治疗老年类风湿关节炎患者的风湿病学家都具有重要意义。
ClinicalTrials.gov标识符：NCT02585258。于2015年10月20日注册。
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