Elisa Kortela1,2, Mari J Kanerva2, Juha Puustinen3,4,5, Saija Hurme6, Laura Airas7, Anneli Lauhio8, Ulla Hohenthal9, Päivi Jalava-Karvinen9, Tuomas Nieminen10, Taru Finnilä9, Tony Häggblom9, Annukka Pietikäinen11, Mari Koivisto6, Johanna Vilhonen9, Minna Marttila-Vaara9, Jukka Hytönen11,12, Jarmo Oksi9. 1. Department of Clinical Medicine, University of Turku, Turku, Finland. 2. Infectious Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 3. Unit of Neurology, Satakunta Central Hospital, Pori, Finland. 4. Department of Neurology, University of Turku, Turku, Finland. 5. Division of Pharmacology and Pharmacotherapy, University of Helsinki, Helsinki, Finland. 6. Department of Biostatistics, University of Turku, Turku, Finland. 7. Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland. 8. Finnish Medicines Agency, Helsinki, Finland. 9. Department of Infectious Diseases, Turku University Hospital and University of Turku, Turku, Finland. 10. Infectious Diseases Unit, Satakunta Central Hospital, Pori, Finland. 11. Institute of Biomedicine, University of Turku, Turku, Finland. 12. Clinical Microbiology, Turku University Hospital, Turku, Finland.
Abstract
BACKGROUND: Lyme neuroborreliosis (LNB) is often treated with intravenous ceftriaxone even if doxycycline is suggested to be noninferior to ceftriaxone. We evaluated the efficacy of oral doxycycline in comparison to ceftriaxone in the treatment of LNB. METHODS:Patients with neurological symptoms suggestive of LNB without other obvious reasons were recruited. The inclusion criteria were (1) production of Borrelia burgdorferi-specific antibodies in cerebrospinal fluid (CSF) or serum; (2) B. burgdorferi DNA in the CSF; or (3) an erythema migrans during the past 3 months. Participants were randomized in a 1:1 ratio to receive either oral doxycycline 100 mg twice daily for 4 weeks, or intravenous ceftriaxone 2 g daily for 3 weeks. The participants described their subjective condition with a visual analogue scale (VAS) from 0 to 10 (0 = normal; 10 = worst) before the treatment, and 4 and 12 months after the treatment. The primary outcome was the change in the VAS score at 12 months. RESULTS:Between 14 September 2012 and 28 December 2017, 210 adults with suspected LNB were assigned to receive doxycycline (n = 104) or ceftriaxone (n = 106). The per-protocol analysis comprised 82 patients withdoxycyclineand 84 patients withceftriaxone. The mean change in the VAS score was -3.9 in the doxycycline group and -3.8 in the ceftriaxone group (mean difference, 0.17 [95% confidence interval, -.59 to .92], which is within the prespecified equivalence margins of -1 to 1 units). Participants in both groups improved equally. CONCLUSIONS:Oral doxycycline is equally effective as intravenous ceftriaxone in the treatment of LNB. CLINICAL TRIALS REGISTRATION: NCT01635530 and EudraCT 2012-000313-37.
RCT Entities:
BACKGROUND:Lyme neuroborreliosis (LNB) is often treated with intravenous ceftriaxone even if doxycycline is suggested to be noninferior to ceftriaxone. We evaluated the efficacy of oral doxycycline in comparison to ceftriaxone in the treatment of LNB. METHODS:Patients with neurological symptoms suggestive of LNB without other obvious reasons were recruited. The inclusion criteria were (1) production of Borrelia burgdorferi-specific antibodies in cerebrospinal fluid (CSF) or serum; (2) B. burgdorferi DNA in the CSF; or (3) an erythema migrans during the past 3 months. Participants were randomized in a 1:1 ratio to receive either oral doxycycline 100 mg twice daily for 4 weeks, or intravenous ceftriaxone 2 g daily for 3 weeks. The participants described their subjective condition with a visual analogue scale (VAS) from 0 to 10 (0 = normal; 10 = worst) before the treatment, and 4 and 12 months after the treatment. The primary outcome was the change in the VAS score at 12 months. RESULTS: Between 14 September 2012 and 28 December 2017, 210 adults with suspected LNB were assigned to receive doxycycline (n = 104) or ceftriaxone (n = 106). The per-protocol analysis comprised 82 patients with doxycycline and 84 patients with ceftriaxone. The mean change in the VAS score was -3.9 in the doxycycline group and -3.8 in the ceftriaxone group (mean difference, 0.17 [95% confidence interval, -.59 to .92], which is within the prespecified equivalence margins of -1 to 1 units). Participants in both groups improved equally. CONCLUSIONS: Oral doxycycline is equally effective as intravenous ceftriaxone in the treatment of LNB. CLINICAL TRIALS REGISTRATION: NCT01635530 and EudraCT 2012-000313-37.