Coates Laura C, Moverley Anna R, McParland Lucy, Brown Sarah, Navarro-Coy Nuria, O'Dwyer John L, Meads David M, Emery Paul, Conaghan Philip G, Helliwell Philip S
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK; Leeds NIHR Musculoskeletal Biomedical Research Unit, Leeds, UK.
Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
Lancet. 2015 Dec 19;386(10012):2489-98. doi: 10.1016/S0140-6736(15)00347-5. Epub 2015 Oct 1.
Early intervention and tight control of inflammation optimise outcomes in rheumatoid arthritis but these approaches have not yet been studied in psoriatic arthritis. We aimed to assess the effect of tight control on early psoriatic arthritis using a treat-to-target approach.
For this open-label multicentre randomised controlled trial, adult patients (aged ≥18 years) with early psoriatic arthritis (<24 months symptom duration), who had not previously received treatment with any disease-modifying anti-rheumatic drugs, were enrolled from eight secondary care rheumatology centres in the UK. Enrolled patients were randomly assigned in a 1:1 ratio to receive either tight control (with review every 4 weeks and with escalation of treatment if minimal disease activity criteria not met) or standard care (standard therapy according to the treating clinician, with review every 12 weeks) for 48 weeks. Randomisation was done by minimisation incorporating a random element, to ensure treatment groups were balanced for randomising centre and pattern of arthritis (oligoarticular vs polyarticular). The randomisation procedure was done through a central 24-h automated telephone system based at the Leeds Institute of Clinical Trials Research (Leeds, UK). This was an open-label study in which patients and clinicians were aware of treatment group assignment. Clinical outcomes were recorded by a masked assessor every 12 weeks. The primary outcome was the proportion of patients achieving an American College of Rheumatology (ACR) 20% (ACR20) response at 48 weeks, analysed by intention to treat with multiple imputation for missing ACR components. Cost-effectiveness was also assessed. This trial is registered with ClinicalTrials.gov, number NCT01106079, and the ISCRCTN registry, number ISCRCTN30147736.
Between May 28, 2008, and March 21, 2012, 206 eligible patients were enrolled and randomly assigned to receive tight control (n=101) or standard care (n=105). In the intention-to-treat patient population, the odds of achieving an ACR20 response at 48 weeks were higher in the tight control group than in the standard care group (odds ratio 1·91, 95% CI 1·03-3·55; p=0·0392). Serious adverse events were reported by 20 (10%) patients (25 events in 14 [14%] patients in the tight control group and eight events in six [6%] patients in the standard care group) during the course of the study. No unexpected serious adverse events or deaths occurred.
Tight control of psoriatic arthritis disease activity through a treat-to-target approach significantly improves joint outcomes for newly diagnosed patients, with no unexpected serious adverse events reported.
Arthritis Research UK and Pfizer.
早期干预和严格控制炎症可优化类风湿关节炎的治疗效果，但这些方法尚未在银屑病关节炎中进行研究。我们旨在采用达标治疗方法评估严格控制对早期银屑病关节炎的影响。
在这项开放标签的多中心随机对照试验中，从英国8个二级医疗风湿病中心招募了成年患者（年龄≥18岁），这些患者患有早期银屑病关节炎（症状持续时间<24个月），且此前未接受过任何改善病情抗风湿药物的治疗。将入选患者按1:1的比例随机分配，分别接受严格控制（每4周复查一次，若未达到最小疾病活动标准则加强治疗）或标准治疗（根据主治医生的标准疗法，每12周复查一次），为期48周。随机化采用包含随机因素的最小化法进行，以确保治疗组在随机化中心和关节炎类型（少关节型与多关节型）方面保持平衡。随机化程序通过位于英国利兹临床试验研究中心的中央24小时自动电话系统进行。这是一项开放标签研究，患者和临床医生知晓治疗组分配情况。临床结局由一名盲态评估者每12周记录一次。主要结局是在48周时达到美国风湿病学会（ACR）20%反应（ACR20）的患者比例，采用意向性分析，并对缺失的ACR成分进行多重填补。同时还评估了成本效益。该试验已在ClinicalTrials.gov注册，注册号为NCT01106079，在国际标准随机对照试验编号注册库注册，注册号为ISCRCTN30147736。
在2008年5月28日至2012年3月21日期间，206例符合条件的患者被纳入并随机分配接受严格控制（n = 101）或标准治疗（n = 105）。在意向性分析的患者群体中，严格控制组在48周时达到ACR20反应的几率高于标准治疗组（优势比1.91，95%置信区间1.03 - 3.55；p = 0.0392）。在研究过程中，20例（10%）患者报告了严重不良事件（严格控制组14例[14%]患者发生25起事件，标准治疗组6例[6%]患者发生8起事件）。未发生意外的严重不良事件或死亡。
通过达标治疗方法严格控制银屑病关节炎疾病活动，可显著改善新诊断患者的关节结局，且未报告意外的严重不良事件。
英国关节炎研究协会和辉瑞公司。
