Randomized Trial of Longer-Term Therapy for Symptoms Attributed to Lyme Disease
Randomized Trial of Longer-Term Therapy for Symptoms Attributed to Lyme Disease
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DOI：
10.1056/nejmoa1505425
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发表时间：
2016-03-31
影响因子：
158.5
通讯作者：
Kullberg, Bart Jan
中科院分区：
文献类型：
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作者：
Berende, Anneleen;ter Hofstede, Hadewych J. M.;Kullberg, Bart Jan
背景莱姆病持续症状的治疗仍存在争议。我们评估了是否长期抗生素治疗莱姆病的持续症状导致更好的结果比短期treatment. METHODS在欧洲进行的随机，双盲，安慰剂对照试验，我们将莱姆病引起的持续症状的患者分为两组，一组与已证实的莱姆病暂时相关，另一组伴有伯氏疏螺旋体IgG或IgM免疫印迹试验阳性，接受为期12周的强力霉素、克拉霉素加羟氯喹或安慰剂口服治疗。所有研究组在开始随机化方案前均接受开放标签静脉注射头孢曲松2周。主要结果测量是健康相关的生活质量，通过兰德-36健康状况量表的身体组成部分汇总评分进行评估（兰德SF-36）（范围：15 - 61，评分越高表明生活质量越好），在第14周治疗期结束时，在完成头孢曲松的2周疗程和随机研究药物或安慰剂的12周疗程后。在进行随机化的281名患者中，280例患者被纳入改良的意向治疗分析（多西环素组86例，克拉霉素-羟氯喹组96例，安慰剂组98例）。在治疗期结束时，SF-36身体成分总评分在三个研究组之间没有显著差异，平均评分为35.0（95%置信区间[CI]，33.5至36.5），多西环素组，35.6克拉霉素-羟氯喹组（95% CI，34.2 - 37.1）和（95% CI，33.4 - 36.2）（P = 0.69;多西环素组与安慰剂组的差异为0.2 [95%CI，-2.4至2.8]，-1.6至3.3];在随后的研究访视中，各组之间的评分也没有显著差异（P = 0.35）。在所有研究组中，SF-36身体成分总评分从基线到治疗期结束显著增加（P
BACKGROUNDThe treatment of persistent symptoms attributed to Lyme disease remains controversial. We assessed whether longer-term antibiotic treatment of persistent symptoms attributed to Lyme disease leads to better outcomes than does shorter-term treatment.METHODSIn a randomized, double-blind, placebo-controlled trial conducted in Europe, we assigned patients with persistent symptoms attributed to Lyme disease - either related temporally to proven Lyme disease or accompanied by a positive IgG or IgM immunoblot assay for Borrelia burgdorferi - to receive a 12-week oral course of doxycycline, clarithromycin plus hydroxychloroquine, or placebo. All study groups received open-label intravenous ceftriaxone for 2 weeks before initiating the randomized regimen. The primary outcome measure was health-related quality of life, as assessed by the physical-component summary score of the RAND-36 Health Status Inventory (RAND SF-36) (range, 15 to 61, with higher scores indicating better quality of life), at the end of the treatment period at week 14, after the 2-week course of ceftriaxone and the 12-week course of the randomized study drug or placebo had been completed.RESULTSOf the 281 patients who underwent randomization, 280 were included in the modified intention-to-treat analysis (86 patients in the doxycycline group, 96 in the clarithromycin-hydroxychloroquine group, and 98 in the placebo group). The SF-36 physical-component summary score did not differ significantly among the three study groups at the end of the treatment period, with mean scores of 35.0 (95% confidence interval [CI], 33.5 to 36.5) in the doxycycline group, 35.6 (95% CI, 34.2 to 37.1) in the clarithromycin-hydroxychloroquine group, and 34.8 (95% CI, 33.4 to 36.2) in the placebo group (P = 0.69; a difference of 0.2 [95% CI, -2.4 to 2.8] in the doxycycline group vs. the placebo group and a difference of 0.9 [95% CI, -1.6 to 3.3] in the clarithromycin-hydroxychloroquine group vs. the placebo group); the score also did not differ significantly among the groups at subsequent study visits (P = 0.35). In all study groups, the SF-36 physical-component summary score increased significantly from baseline to the end of the treatment period (P