A reappraisal of the u.s. Clinical trials of post-treatment lyme disease syndrome.
Fallon BA1, Petkova E, Keilp JG, Britton CB.
Abstract
Four federally funded randomized placebo-controlled treatment trials of post-treatment Lyme syndrome in the United States have been conducted. Most international treatment guidelines summarize these trials as having shown no acute or sustained benefit to repeated antibiotic therapy. The goal of this paper is to determine whether this summary con-clusion is supported by the evidence.
METHODS:
The methods and results of the 4 U.S. treatment trials are described and their critiques evaluated.
RESULTS:
2 of the 4 U.S. treatment trials demonstrated efficacy of IV ceftriaxone on primary and/or secondary outcome measures.
CONCLUSIONS:
Future treatment guidelines should clarify that efficacy of IV ceftriaxone for post-treatment Lyme fatigue was demonstrated in one RCT and supported by a second RCT, but that its use was not recommended primarily due to adverse events stemming from the IV route of treatment. While repeated IV antibiotic therapy can be effective, safer modes of delivery are needed.
Volledige tekst:
https://benthamopen.com/FULLTEXT/TONEUJ-6-79
FINAL COMMENTS
The conclusions of this analysis of the chronic Lyme trials emphasize the benefits of repeated antibiotic therapy for patients with specific chronic symptoms. This is done as a counterbalance to the majority of published guidelines which overlook and/or dismiss the evidence that demonstrates that additional antibiotic therapy can lead to sustained benefit. We hope that our review will lead to more carefully detailed and balanced summaries in future guidelines. However, we also wish to emphasize that while some patients do improve with repeated antibiotic therapy, other patients with persistent symptoms do not. Further, as the clinical trials also demonstrate, antibiotic therapy particularly when given intravenously can put the patient at serious risk.
Biomarkers are needed that can help clinicians to discriminate in advance which patients are more likely to benefit from repeated antibiotic therapy vs. those for whom such treatment is unlikely to be beneficial. Future studies must also begin to address non-antibiotic strategies to help improve persistent symptoms. Recent serologic and CSF studies of patients with post-treatment Lyme disease syndrome suggest that a persistently activated immune response may play a role in the pathophysiology of chronic symptoms [15, 16] . Clarification of whether these findings are of pathogenic relevance and whether this immune activation is due to persistent antigenic stimulation (as might occur from persistent Borrelia) or from a post-infectious autoimmune process would be quite beneficial to clinicians seeking to identify more effective and appropriately targeted treatments for these patients.