Durcan Laura, Clarke William A, Magder Laurence S, Petri Michelle
From the Department of Rheumatology, Johns Hopkins University School of Medicine; Department of Pathology, Clinical Chemistry, Johns Hopkins University Hospital, Baltimore; Department of Epidemiology and Public Health, University of Maryland, College Park, Maryland, USA.L. Durcan, MD, Department of Rheumatology, Johns Hopkins University School of Medicine; W.A. Clarke, PhD, Department of Pathology, Clinical Chemistry, Johns Hopkins University Hospital; L.S. Magder, MPH, PhD, Department of Epidemiology and Public Health, University of Maryland; M. Petri, MD, MPH, Department of Rheumatology, Johns Hopkins University School of Medicine.
J Rheumatol. 2015 Nov;42(11):2092-7. doi: 10.3899/jrheum.150379. Epub 2015 Oct 1.
Hydroxychloroquine (HCQ) is used for its effect on systemic lupus erythematosus (SLE) disease activity and longterm benefits. This can be limited by adherence. One way to assess adherence is to measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is disagreement about dosing; rheumatologists recommend weight-based dosing while some other specialists advocate height-based "ideal body weight" dosing.
Patients were prescribed HCQ not exceeding 6.5 mg/kg (max 400 mg/day). In hemodialysis, the dose was 200 mg after each session, and in renal insufficiency it was 200 mg/day. Levels were measured at each visit with a therapeutic range of 500-2000 ng/ml. Patients were divided according to baseline blood level. To assess the effect of measurement and counseling on adherence, we compared the proportion of patients with a level of 500 ng/ml or higher based on the number of prior assessments.
The proportion of patients with HCQ levels in the therapeutic range differed significantly by age, sex, and Vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height and ideal body weight. Comparing those with undetectable, subtherapeutic, and therapeutic levels, disease activity decreased (SLE Disease Activity Index 2.92, 2.36, and 2.20, p = 0.04 for trend). At first, 56% were therapeutic, and by the third measurement this increased to 80% (p ≤ 0.0001).
There was a trend toward higher disease activity with lower HCQ levels. Renal failure dosing led to suboptimum levels. We show that weight-based dosing (max 400 mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling, and repeated testing can increase adherence rates.
羟氯喹（HCQ）因其对系统性红斑狼疮（SLE）疾病活动的影响及长期益处而被使用。这可能会受到依从性的限制。评估依从性的一种方法是测量血液水平。关于血液水平和疾病活动存在相互矛盾的数据。在给药剂量方面存在分歧；风湿病学家推荐基于体重给药，而其他一些专家则主张基于身高的“理想体重”给药。
给患者开具的HCQ剂量不超过6.5毫克/千克（最大400毫克/天）。在血液透析中，每次透析后剂量为200毫克，在肾功能不全时剂量为200毫克/天。每次就诊时测量血药浓度，治疗范围为500 - 2000纳克/毫升。患者根据基线血液水平进行分组。为了评估测量和咨询对依从性的影响，我们根据之前评估的次数比较了血药浓度达到500纳克/毫升或更高的患者比例。
HCQ血药浓度在治疗范围内的患者比例在年龄、性别和维生素D水平方面存在显著差异。肾衰竭患者的血药浓度有降低趋势。无论身高和理想体重如何，血药浓度相似。比较血药浓度不可检测、低于治疗水平和处于治疗水平的患者，疾病活动度降低（SLE疾病活动指数分别为2.92、2.36和2.20，趋势p = 0.04）。起初，56%的患者血药浓度处于治疗水平，到第三次测量时，这一比例增至80%（p≤0.0001）。
HCQ水平较低时疾病活动度有升高趋势。肾衰竭时的给药导致血药浓度不理想。我们表明基于体重给药（最大每日400毫克）是合适的，且身高似乎不影响血药浓度。测量、咨询和重复检测可提高依从率。
