Effects of Hydroxychloroquine on Symptomatic Improvement in Primary Sjogren Syndrome The JOQUER Randomized Clinical Trial
Effects of Hydroxychloroquine on Symptomatic Improvement in Primary Sjogren Syndrome The JOQUER Randomized Clinical Trial
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DOI：
10.1001/jama.2014.7682
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发表时间：
2014-07-16
影响因子：
120.7
通讯作者：
Mariette, Xavier
中科院分区：
文献类型：
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作者：
Gottenberg, Jacques-Eric;Ravaud, Philippe;Mariette, Xavier
原发性干燥综合征是一种全身性自身免疫性疾病，其特征是口眼干燥、疼痛和疲劳。羟氯喹是最常见的免疫抑制剂的综合征。目的评价羟氯喹对原发性干燥综合征主要症状的疗效：干燥、疼痛和疲劳。设计、设置和参与者从2008年4月到2011年5月，来自法国15所大学医院的120名根据美国-欧洲共识组标准的原发性干燥综合征患者被随机分配到一个双盲，平行组安慰剂对照试验。参与者在基线、第12周、第24周（主要结局）和第48周进行评估。最后一名患者的最后一次随访日期为2012年5月15日。干预患者随机（1：1）接受羟氯喹（400 mg/d）或安慰剂治疗，直至第24周。所有患者在第24 - 48周服用羟氯喹。主要结果和测量主要终点是在第0 - 24周之间，评估干燥、疼痛和疲劳的3个数字模拟量表（从0 [最好]到10 [最差]）中的2个评分降低30%或更多的患者比例。结果：在24周时，羟氯喹组达到主要终点的患者比例为17.9%（10/56），安慰剂组为17.2%（11/64）（比值比，1.01; 95%CI，0.37-2.78; P = 0.98）。在第0周和第24周之间，安慰剂组干燥的平均（SD）数字模拟量表评分从6.38（2.14）变为5.85（2.57），羟氯喹组从6.53（1.97）变为6.22（1.87）。安慰剂组的疼痛平均（SD）数字模拟量表评分从4.92（2.94）变为5.08（2.48），羟氯喹组从5.09（3.06）变为4.59（2.90）。安慰剂组疲劳的平均（SD）数字模拟量表从6.26（2.27）变为5.72（2.38），羟氯喹组从6.00（2.52）变为5.94（2.40）。除1名患者外，羟氯喹组的所有患者都有可检测的血液药物水平。羟氯喹对抗SSA自身抗体、高IgG水平或全身受累患者无效。在第一个24周，有2个严重的不良事件在羟氯喹组和3在安慰剂组;在过去的24周，有3个严重的不良事件在羟氯喹组和4在安慰剂group.CONCLUSIONS和RELEVANCE在原发性干燥综合征患者中，使用羟氯喹与安慰剂相比，在24周的治疗期间没有改善症状。需要进一步的研究来评估长期结果。版权所有2014美国医学会。All rights reserved.
IMPORTANCE Primary Sjogren syndrome is a systemic autoimmune disease characterized by mouth and eye dryness, pain, and fatigue. Hydroxychloroquine is the most frequently prescribed immunosuppressant for the syndrome. However, evidence regarding its efficacy is limited.OBJECTIVE To evaluate the efficacy of hydroxychloroquine for the main symptoms of primary Sjogren syndrome: dryness, pain, and fatigue.DESIGN, SETTING, AND PARTICIPANTS From April 2008 to May 2011, 120 patients with primary Sjogren syndrome according to American-European Consensus Group Criteria from 15 university hospitals in France were randomized in a double-blind, parallel-group, placebo-controlled trial. Participants were assessed at baseline, week 12, week 24 (primary outcome), and week 48. The last follow-up date for the last patient was May 15, 2012.INTERVENTIONS Patients were randomized (1: 1) to receive hydroxychloroquine (400mg/d) or placebo until week 24. All patients were prescribed hydroxychloroquine between weeks 24 and 48.MAIN OUTCOMES AND MEASURES The primary end point was the proportion of patients with a 30% or greater reduction between weeks 0 and 24 in scores on 2 of 3 numeric analog scales (from 0 [best] to 10 [worst]) evaluating dryness, pain, and fatigue. RESULTS At 24 weeks, the proportion of patients meeting the primary end point was 17.9% (10/56) in the hydroxychloroquine group and 17.2%(11/64) in the placebo group (odds ratio, 1.01; 95% CI, 0.37-2.78; P = .98). Between weeks 0 and 24, the mean (SD) numeric analog scale score for dryness changed from 6.38 (2.14) to 5.85 (2.57) in the placebo group and 6.53 (1.97) to 6.22 (1.87) in the hydroxychloroquine group. The mean (SD) numeric analog scale score for pain changed from 4.92 (2.94) to 5.08 (2.48) in the placebo group and 5.09 (3.06) to 4.59 (2.90) in the hydroxychloroquine group. The mean (SD) numeric analog scale for fatigue changed from 6.26 (2.27) to 5.72 (2.38) in the placebo group and 6.00 (2.52) to 5.94 (2.40) in the hydroxychloroquine group. All but 1 patient in the hydroxychloroquine group had detectable blood levels of the drug. Hydroxychloroquine had no efficacy in patients with anti-SSA autoantibodies, high IgG levels, or systemic involvement. During the first 24 weeks, there were 2 serious adverse events in the hydroxychloroquine group and 3 in the placebo group; in the last 24 weeks, there were 3 serious adverse events in the hydroxychloroquine group and 4 in the placebo group.CONCLUSIONS AND RELEVANCE Among patients with primary Sjogren syndrome, the use of hydroxychloroquine compared with placebo did not improve symptoms during 24 weeks of treatment. Further studies are needed to evaluate longer-term outcomes. Copyright 2014 American Medical Association. All rights reserved.