Department of Rheumatology, Service de Rhumatologie, Hôpitaux Universitaires de Strasbourg, Centre de Référence National Pour les Maladies Auto-Immunes Systémiques Rares, Université de Strasbourg, Strasbourg, France.
Department of Epidemiology and Public Health, Hotel Dieu, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
JAMA. 2014 Jul 16;312(3):249-58. doi: 10.1001/jama.2014.7682.
Primary Sjögren 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.
To evaluate the efficacy of hydroxychloroquine for the main symptoms of primary Sjögren syndrome: dryness, pain, and fatigue.
DESIGN, SETTING, AND PARTICIPANTS: From April 2008 to May 2011, 120 patients with primary Sjögren 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.
Patients were randomized (1:1) to receive hydroxychloroquine (400 mg/d) or placebo until week 24. All patients were prescribed hydroxychloroquine between weeks 24 and 48.
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.
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.
Among patients with primary Sjögren 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.
clinicaltrials.gov Identifier: NCT00632866.
原发性干燥综合征是一种以口、眼干燥、疼痛和疲劳为特征的系统性自身免疫性疾病。羟氯喹是最常被开用于治疗该综合征的免疫抑制剂。然而，关于其疗效的证据有限。
评估羟氯喹对原发性干燥综合征的主要症状（干燥、疼痛和疲劳）的疗效。
设计、地点和参与者：2008 年 4 月至 2011 年 5 月，来自法国 15 所大学医院的 120 名符合美国-欧洲共识组标准的原发性干燥综合征患者被随机分为双盲、平行组、安慰剂对照试验。参与者在基线、第 12 周、第 24 周（主要终点）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。
患者随机（1:1）接受羟氯喹（400mg/d）或安慰剂治疗至第 24 周。所有患者在第 24 周至第 48 周期间均接受羟氯喹治疗。
主要终点是在第 0 周至 24 周期间，2 项数字模拟量表（0[最佳]至 10[最差]）中评估干燥、疼痛和疲劳的 3 项评分中有 2 项改善 30%或以上的患者比例。
在 24 周时，羟氯喹组中符合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 周至 24 周期间，安慰剂组干燥症状的数字模拟量表评分从 6.38（2.14）降至 5.85（2.57），羟氯喹组从 6.53（1.97）降至 6.22（1.87）。安慰剂组疼痛的数字模拟量表评分从 4.92（2.94）降至 5.08（2.48），羟氯喹组从 5.09（3.06）降至 4.59（2.90）。安慰剂组疲劳的数字模拟量表评分从 6.26（2.27）降至 5.72（2.38），羟氯喹组从 6.00（2.52）降至 5.94（2.40）。羟氯喹组除 1 名患者外，其余患者均检测到药物的血药水平。羟氯喹对抗 SSA 自身抗体、高 IgG 水平或全身受累的患者无效。在最初的 24 周内，羟氯喹组有 2 例严重不良事件，安慰剂组有 3 例；在最后 24 周内，羟氯喹组有 3 例严重不良事件，安慰剂组有 4 例。
在原发性干燥综合征患者中，与安慰剂相比，使用羟氯喹治疗 24 周并不能改善症状。需要进一步研究来评估长期结果。
clinicaltrials.gov 标识符：NCT00632866。
