25 April 2018

Eddy Adang, Anneleen Berende en Bart Jan Kullberg, showed that shorter-term provision of antibiotics in patients with persistent symptoms attributed to Lyme disease is cost-effective.

Background
The treatment of persistent symptoms attributed to Lyme disease remains controversial. Recently, the PLEASE study did not demonstrate any additional clinical benefit of longer-term versus shorter-term antibiotic treatment. However, the economic impact of the antibiotic strategies has not been investigated.
Methods
This prospective economic evaluation, adhering a societal perspective, was performed alongside the PLEASE study, a multicenter, placebo-controlled, double-blind 1:1:1 randomized clinical trial in which all patients received open-label intravenous ceftriaxone for two weeks before the 12-week randomized blinded oral antibiotic regimen (doxycycline, clarithromycin plus hydroxychloroquine, or placebo). Between 2010 and 2013, patients (n = 271) with borreliosis-attributed persistent symptoms were enrolled and followed for one year. Main outcomes were costs, quality-adjusted life years, and incremental net monetary benefit of longer-term versus shorter-term antibiotic therapy.
Results
Mean quality-adjusted life years (95% CI) were not significantly different (p = 0.96): 0.82 (0.77–0.88) for ceftriaxone/doxycycline (n = 82), 0.81 (0.76–0.88) for ceftriaxone/clarithromycin-hydroxychloroquine (n = 93), and 0.81 (0.76–0.86) for ceftriaxone/placebo (n = 96). Total societal costs per patient (95% CI) were not significantly different either (p = 0.35): €11,995 (€8,823-€15,670) for ceftriaxone/doxycycline, €12,202 (€9,572-€15,253) for ceftriaxone/clarithromycin-hydroxychloroquine, and €15,249 (€11,294-€19,781) for ceftriaxone/placebo. Incremental net monetary benefit (95% CI) for ceftriaxone/doxycycline compared to ceftriaxone/placebo varied from €3,317 (-€2,199-€8,998) to €4,285 (-€6,085-€14,524) over the willingness-to-pay range, and that of ceftriaxone/clarithromycin-hydroxychloroquine compared to ceftriaxone/placebo from €3,098 (-€888-€7,172) to €3,710 (-€4,254-€11,651). For every willingness-to-pay threshold, the incremental net monetary benefits did not significantly differ from zero.
Conclusion
The longer-term treatments were similar with regard to costs, effectiveness and cost-effectiveness compared to shorter-term treatment in patients with borreliosis-attributed persistent symptoms after one year of follow-up. Given the results of this study, and taking into account the external costs associated with antibiotic resistance, the shorter-term treatment is the antibiotic regimen of first choice.

This research was conducted within the themes of Healthcare improvement science and Infectious diseases and global health.

Publication
Cost-effectiveness of longer-term versus shorter-term provision of antibiotics in patients with persistent symptoms attributed to Lyme disease.
Berende A, Nieuwenhuis L, Ter Hofstede HJM, Vos FJ, Vogelaar ML, Tromp M, van Middendorp H, Donders ART, Evers AWM, Kullberg BJ, Adang EMM.
 

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