低疾病活动度银屑病患者生物制剂剂量的严格控制减少：一项随机实用非劣效性试验
Tight controlled dose reduction of biologics in psoriasis patients with low disease activity: a randomized pragmatic non-inferiority trial.
作者信息
Atalay Selma, van den Reek Juul M P A, van Vugt Lieke J, Otero Marisol E, van de Kerkhof Peter C M, den Broeder Alfons A, Kievit Wietske, de Jong Elke M G J
机构信息
Department of Dermatology, Radboud University Medical Center, Rene Descartesdreef 1, 6525 GL, Nijmegen, The Netherlands.
Department of Rheumatology, Sint Maartenskliniek, Hengstdal 3, 6574 NA, Ubbergen, Nijmegen, The Netherlands.
出版信息
BMC Dermatol. 2017 May 8;17(1):6. doi: 10.1186/s12895-017-0057-6.
BACKGROUND
Psoriasis is an immune-mediated chronic inflammatory skin disorder for which several targeted biologic therapies became available in the last 10 years. Data from patients with rheumatoid arthritis revealed that dose tapering combined with tight control of disease activity is successful. For psoriasis patients the lowest effective dose of biologics needs to be determined. The objective was to assess whether dose tapering of biologics guided by Psoriasis Area and Severity Index (PASI) and Dermatology Quality of Life Index (DLQI) scores in psoriasis patients with controlled disease activity is non-inferior (NI) to usual care.
METHODS/DESIGN: This is a multicenter, pragmatic, randomized, non-inferiority trial with cost- effectiveness analysis. One hundred and twenty patients with stable low disease activity (PASI ≤ 5 and DLQI ≤ 5) for at least 6 months with a stable use of adalimumab, etanercept or ustekinumab will be randomized 1:1 to the dose reduction group or usual care. In the dose reduction group, the treatment intervals will be prolonged stepwise, resulting in a 33% and 50% dose reduction, respectively. Disease activity is monitored every three months with PASI and DLQI. In case of flare the treatment is adjusted to the previous effective dose. The primary outcome (PASI) at 12 months will be analyzed with ANCOVA in which the baseline PASI will be included as covariate to gain efficiency. The secondary outcomes include number of and time to disease flares, health-related quality of life, serious adverse events, and costs.
DISCUSSION
With this study we want to assess whether disease activity guided dose reduction of biologics can be achieved for psoriasis patients with low stable disease activity, without losing disease control. By using the lowest effective dose of biologics, we expect to minimize side effects and save costs.
TRIAL REGISTRATION
This trial was registered at ClinicalTrials.gov ( NCT 02602925 ). Trial registration date October 9 2015.
背景
银屑病是一种免疫介导的慢性炎症性皮肤病，在过去10年中有几种靶向生物疗法可供使用。类风湿性关节炎患者的数据显示，减量联合严格控制疾病活动是成功的。对于银屑病患者，需要确定生物制剂的最低有效剂量。目的是评估在疾病活动得到控制的银屑病患者中，以银屑病面积和严重程度指数（PASI）和皮肤病生活质量指数（DLQI）评分指导生物制剂减量是否不劣于常规治疗。
方法/设计：这是一项多中心、实用、随机、非劣效性试验，并进行成本效益分析。120例至少6个月病情稳定、疾病活动度低（PASI≤5且DLQI≤5）、稳定使用阿达木单抗、依那西普或乌司奴单抗的患者将按1:1随机分为减量组或常规治疗组。在减量组中，治疗间隔将逐步延长，分别导致剂量减少33%和50%。每三个月用PASI和DLQI监测疾病活动度。如果病情复发，治疗将调整为先前的有效剂量。12个月时的主要结局（PASI）将采用协方差分析进行分析，其中将基线PASI作为协变量纳入以提高效率。次要结局包括疾病复发的次数和时间、健康相关生活质量、严重不良事件和成本。
讨论
通过本研究，我们想评估对于疾病活动度低且稳定的银屑病患者，是否可以在不失去疾病控制的情况下实现生物制剂的疾病活动度指导下的减量。通过使用生物制剂的最低有效剂量，我们期望将副作用降至最低并节省成本。
试验注册
本试验已在ClinicalTrials.gov注册（NCT 02602925）。试验注册日期为2015年10月9日。
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