Netherlands Lyme Trial: Persistent Symptoms After Treatment

QUALITY OF LIFE REMAINED POOR AFTER TREATMENT
SOME PATIENTS CONTINUED TO EXPERIENCE PTLDS
THE DEBATE OVER LONG-TERM OUTCOMES CONTINUES

Participants in the PLEASE trial were scored using an SF-36 physical component of health (PCS) scale. Their PCS scores of 31 to 32 were worse than those reported for diabetic and cancer patients. [3] These patients’ PCS scores were reported to be 42 and 41, respectively, while PCS scores for the general population averaged 50. [4]

Furthermore, the quality of life for Lyme disease patients in the Netherlands trial remained poor whether they were prescribed a 2-week or 14-week course of antibiotics. Their PCS scores rose by only three points to 34 and 35, [3] leaving their quality of life worse than that reported for diabetic or cancer patients or the general population. [4]

The author of a companion editorial sought to minimize the significance of these poor outcomes.

“These patients may, however, take small comfort in a recent study of longer-term outcomes after culture confirmed Lyme disease that showed that mental and physical health scores had returned to baseline scores similar to those of the age adjusted U.S. population,” concluded Melia from Johns Hopkins University School of Medicine. [5]

However, the study described by Melia does not necessarily offer such reassurance upon closer inspection.

In the longer-term outcome study, 11% of participants suffered from Post-Treatment Lyme Disease Syndrome (PTLDS) 11 to 20 years after treatment. [6]

PTLDS was described as “persistent symptoms, defined by either fatigue, musculoskeletal pain in at least three areas of the body, and/or cognitive complaints of difficulty finding words, focusing, concentrating or memory impairment and functional impairment on a Short Form (36) Health Survey (SF-36).” [6]

Nor can Lyme disease patients take comfort when reviewing the findings of another long-term outcome study conducted at Johns Hopkins University School of Medicine.

Investigators reported that 11 (14.47%) of their patients suffered from PTLDS at either the 6- or 12-month follow-up visit, despite receiving a one-time, 3-week course of doxycycline. An additional 29 (38.16%) remained symptomatic. Only 36 (47.37%) of the Johns Hopkins patients returned to their usual health at six and twelve months. [7]

Questions Following the Netherlands Trial

The study investigators did not call for better outcomes. [3,5,8]

They could have encouraged physicians to avoid treatment delays, which have averaged 1.9 years in some reports. [3]

In addition, the investigators could also have recommended evaluations for coinfections such as Babesia, which may require alternative treatment strategies. [9]

Finally, investigators could have explored alternative treatment regimens rather than a two-week course of intravenous (IV) ceftriaxone followed by a 12-week oral course of doxycycline, clarithromycin plus hydroxychloroquine, or placebo.

For example, the PLEASE investigators could have prescribed 4 weeks of IV ceftriaxone instead of two, [10,11] given that 4 weeks of IV ceftriaxone has already been shown to be more effective for chronic manifestations of Lyme disease.

Four weeks of IV ceftriaxone was more effective than placebo in one of the Krupp NIH-sponsored clinical trials. [12]

Ten weeks of IV ceftriaxone was more effective than placebo for fatigue, though not for cognitive function, in the Fallon NIH-sponsored clinical trial. [2]

To learn more about the Netherlands clinical trial results, watch the All Things Lyme video blog, Netherlands Trial Does Not Support Short-term Therapy for Lyme disease.

References:

1. Klempner MS. Controlled trials of antibiotic treatment in patients with post-treatment chronic Lyme disease. Vector Borne Zoonotic Dis. 2002;2(4):255-263.
2. Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. 2008;70(13):992-1003.
3. Berende A, ter Hofstede HJ, Vos FJ, et al. Randomized Trial of Longer-Term Therapy for Symptoms Attributed to Lyme Disease. N Engl J Med. 2016;374(13):1209-1220.
4. Cameron D. Severity of Lyme disease with persistent symptoms. Insights from a double-blind placebo-controlled clinical trial. Minerva Med. 2008;99(5):489-496.
5. Melia MT, Lantos PM, Auwaerter PG. Lyme Disease: Authentic Imitator or Wishful Imitation? JAMA Neurol. 2014.
6. Weitzner E, Visintainer P, Wormser GP. Comparison of males versus females with culture-confirmed early Lyme disease at presentation and at 11-20 years after diagnosis. Diagn Microbiol Infect Dis. 2016.
7. Aucott JN, Soloski MJ, Rebman AW, et al. CCL19 as a Chemokine Risk Factor for Post-Treatment Lyme Disease Syndrome: A Prospective Clinical Cohort Study. Clin Vaccine Immunol. 2016.
8. Wormser GP. Longer-Term Therapy for Symptoms Attributed to Lyme Disease. N Engl J Med. 2016;375(10):997.
9. Diuk-Wasser MA, Vannier E, Krause PJ. Coinfection by Ixodes Tick-Borne Pathogens: Ecological, Epidemiological, and Clinical Consequences. Trends Parasitol. 2015.
10. Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med. 1990;323(21):1438-1444.
11. Logigian EL, Kaplan RF, Steere AC. Successful treatment of Lyme encephalopathy with intravenous ceftriaxone. J Infect Dis. 1999;180(2):377-383.
12. Krupp LB, Hyman LG, Grimson R, et al. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology. 2003;60(12):1923-1930.

Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.

Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention