Six versus 2 weeks treatment with doxycycline in European Lyme neuroborreliosis: a multicentre, non-inferiority, double-blinded, randomised and placebo-controlled trial

Abstract

BackgroundThere is limited evidence regarding optimal duration of antibiotic treatment in neuroborreliosis. We aimed to compare efficacy and safety of oral doxycycline for 2 and 6 weeks in European Lyme neuroborreliosis (LNB).MethodsThe trial had a randomised, double-blinded, placebo-controlled, non-inferiority design. Patients with LNB were recruited from eight Norwegian hospitals and randomised to doxycycline 200 mg once daily for 2 weeks, followed by 4 weeks of placebo, or doxycycline 200 mg once daily for 6 weeks. The primary endpoint was clinical improvement as measured by difference in a Composite Clinical Score (0–64 points) from baseline to 6 months. The non-inferiority margin was predetermined to 0.5 points.ResultsOne hundred and twenty-one patients were included. Fifty-two treated for 2 weeks and 53 for 6 weeks were included in the intention-to-treat analyses, and 52 and 51 in per-protocol analysis. Mean difference in clinical improvement between the groups was 0.06, 95% CI −1.2 to 1.2, p=0.99 in the intention-to-treat population, and −0.4, 95% CI −1.4 to 0.7, p=0.51 in the per-protocol population and non-inferiority could not be established. There were no treatment failures and no serious adverse events. The groups did not differ in secondary outcomes including clinical scores at 10 weeks and 12 months, cerebrospinal fluid data and patient-reported outcome measures. Patients receiving 6 weeks doxycycline reported slightly more side effects in week 5.ConclusionOur results strongly indicate that there are no benefits of doxycycline treatment beyond 2 weeks in European LNB.Trial registration number2015-001481-25.

Efficacy and safety of pharmacological treatments for Lyme neuroborreliosis: An updated systematic review

“…To update an assessment of the available literature on treatment of LNB, a comprehensive literature search was performed. For the first time, high-quality evidence from an RCT with low risk of bias is available regarding extended antibiotic treatment in LNB [12]. This much-needed new evidence closes a previous evidence gap [1].…”

“…Our search identified one RCT reporting data on length of treatment in LNB [12]. Solheim et al compared 2 vs. 6 weeks of treatment with oral doxycycline 200 mg.…”

“…Characteristics of included studies are shown in Table 1. Two studies were RCTs [12,13] five were NRS [14][15][16][17][18]. Data from one RCT regarding choice of antibiotic treatment could be integrated in a meta-analysis of previous studies.…”

“…One RCT had an overall low risk of bias [12] and one RCT was unblinded [13] and therefore had ratings of 'high risk of bias' in the respective items (Figure S1). Risk of bias in NRS was generally high, leading to an overall assessment as 'critical' risk of bias in all studies according to the ROBINS-I-tool (Figure S2).…”

Assessment of cognitive function, structural brain changes and fatigue 6 months after treatment of neuroborreliosis

“…Furthermore, the majority of patients reporting mild problems (81.3%) had scores within normal range. The item subjective concentration/ memory problem is part of a clinical composite score that is unvalidated, but has been used in previous clinical studies [ 42 , 43 ]. Since none of the controls were asked to grade subjective memory or concentration problems, and the clinical composite score is unvalidated, we do not know whether mild subjective concentration/ memory problems are frequent in the control group or the general population.…”