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N Engl J Med. 2016 Mar 31;374(13):1209-20. doi: 10.1056/NEJMoa1505425.

Randomized Trial of Longer-Term Therapy for Symptoms Attributed to Lyme Disease.

Author information

1
From the Departments of Medicine (A.B., H.J.M.H., F.J.V., M.L.V., M.T., B.J.K.), Medical Psychology (H.M., M.L.V., A.W.M.E.), Rheumatology (F.H.), and Health Evidence (A.R.T.D.) and the Radboud Center for Infectious Diseases (A.B., H.J.M.H., F.J.V., M.L.V., M.T., B.J.K.), Radboud University Medical Center, and Sint Maartenskliniek (F.J.V., F.H.), - both in Nijmegen, and the Health, Medical, and Neuropsychology Unit, Institute of Psychology, Leiden University, Leiden (H.M., A.W.M.E.) - all in the Netherlands.

Abstract

BACKGROUND:

The 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.

METHODS:

In 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.

RESULTS:

Of 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<0.001). The rates of adverse events were similar among the study groups. Four serious adverse events thought to be related to drug use occurred during the 2-week open-label ceftriaxone phase, and no serious drug-related adverse event occurred during the 12-week randomized phase.

CONCLUSIONS:

In patients with persistent symptoms attributed to Lyme disease, longer-term antibiotic treatment did not have additional beneficial effects on health-related quality of life beyond those with shorter-term treatment. (Funded by the Netherlands Organization for Health Research and Development ZonMw; PLEASE ClinicalTrials.gov number, NCT01207739.).

PMID:
27028911
DOI:
10.1056/NEJMoa1505425
[Indexed for MEDLINE]
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