Long-Term Antibiotics No Benefit for Chronic Lyme Disease Symptoms

The results of a double-blind, randomized, placebo-controlled trial in patients with persistent symptoms of Lyme disease have shown that long-term antibiotic treatment does not lead to better outcomes than short-term antibiotic treatment does.

The findings from the Persistent Lyme Empiric Antibiotic Study Europe (PLEASE) trial were published by Anneleen Berende, MD, from Radboud University Medical Center, Nijmegen, the Netherlands, and colleagues in the New England Journal of Medicine on March 31.

According to the authors, “[i]n this randomized, double-blind trial involving patients with persistent symptoms attributed to Lyme disease, prolonged antibiotic treatment (ceftriaxone followed by 12 weeks of either doxycycline or clarithromycin—hydroxychloroquine) did not lead to a better health-related quality of life [QOL] than that with shorter-term treatment (ceftriaxone followed by placebo).”

Lyme disease is caused by the spirochete Borrelia burgdorferi, which is transmitted to humans through the bite of infected blacklegged ticks. Although only a small proportion of people who are bitten by an infected tick will develop Lyme disease, if untreated, the disease can be associated with a range of signs and symptoms, depending on the stage of infection. These include headache, fever, swollen lymph nodes, fatigue, and muscle and joint aches. The characteristic erythema migrans rash also occurs in up to 90% of infected people—this arises at the site of a tick bite and may enlarge and take on a “bull’s eye” appearance.

Borrelia burgdorferi

In many patients, treatment with antibiotics will completely cure Lyme disease. Therapy typically lasts between 10 days and 28 days and commonly involves oral administration of doxycycline, amoxicillin, or cefuroxime axetil. Nevertheless, even after appropriate treatment, up to 20% of patients with Lyme disease experience long-lasting symptoms, such as pain, fatigue, and problems with memory or concentration.

However, substantial medical controversy surrounds the treatment of persistent Lyme disease symptoms, as well as whether this chronic form of the disease even exists.

In particular, although most treatment guidelines recommend antibiotic treatment for 2 to 4 weeks in these cases, physicians continue to debate whether longer treatment could be beneficial.

Researchers therefore designed the PLEASE trial in patients with persistent symptoms of Lyme disease, to investigate whether long-term antibiotic treatment leads to better results than standard treatment does.

The study included 280 participants who were previously diagnosed with Lyme disease and had persistent symptoms such as fatigue, muscle and joint pain, and concentration problems.

After an initial 2-week course of ceftriaxone (2,000 mg intravenous), participants were randomly assigned to a 12-week oral regimen of one of 3 treatments: doxycycline (100 mg twice daily); a combination of clarithromycin (500 mg twice daily) and hydroxychloroquine (200 mg twice daily); or placebo.

At the end of randomized treatment period (week 14), no differences were seen between the 3 groups on the Short Form (SF)-36 physical component summary scores. SF-36 is a patient-reported questionnaire about aspects of patient health, including symptoms, QOL, and wellbeing. The SF-36 score was 35 (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=.69).

However, although the mean SF-36 score improved significantly from baseline to the end of the treatment period in all groups, participants’ QOLremained lower than that of the general population, the authors add.

In an accompanying editorial in the journal, Michael T. Melia, MD, and Paul G. Auwaerter, MD, both from Johns Hopkins University School of Medicine, Baltimore, Maryland, note the importance of these findings from the PLEASE study. They stress that “[p]atients with subjective, vexing symptoms attributed to Lyme disease should not anticipate that even longer courses of antibiotics will produce relief, a finding that is in concert with results from previous trials.”

“Though prolonged antibiotic therapy is not the answer, we do not know what is truly helpful,” the authors conclude.

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.