PLEASE5+: Long-term outcomes and quality of life of patients with symptoms attributed to Lyme borreliosis

After antibiotic treatment for Lyme borreliosis, 5-20% of patients report
persistent symptoms for months to years. The effect of longer-term antibiotic
treatment on these symptoms has been investigated in several studies, of which
the Persistent Lyme Empiric Antibiotic Study Europe (PLEASE) study is the
largest and most recent. Patients with persistent symptoms attributed to Lyme
borreliosis were randomized into three arms to receive 3 months of doxycycline,
clarithromycin/hydroxychloroquine, or placebo, after a standardized two weeks
course of intravenous ceftriaxone. Patients were followed for up to one year.
No beneficial effects were reported on neurological, neuropsychological, or
quality-of-life endpoints.
Although persistent infection has not been demonstrated to be the cause of
persistent symptoms in humans after antibiotic treatment, and results of
randomized trials do not support prolonged antibiotic treatment for these
symptoms, individual patients do report improvement of their health status
after long-term antibiotic treatment or complementary therapies. After
completion of the study visits, many patients in the PLEASE cohort might have
continued the search for improving their persistent symptoms, both in regular
and complementary health settings.
The aims of the PLEASE5+ study are to investigate the outcomes of the PLEASE
participants at the longer term (between 5-8 year after PLEASE participation),
as well as the impact of persistent symptoms attributed to Lyme borreliosis on
work(ability). Based on the long-term outcomes in this cohort, predictors for
the course of disease and ability to work will be explored. Furthermore, blood
and urine samples will be collected for research on immunological and metabolic
parameters and their potential influence on the course of persistent symptoms
in these patients.

The primary objective is to assess the long-term (5-8 years) quality of life in
patients who previously participated in the placebo-controlled randomized
controlled trial on the effect of prolonged antibiotic treatment on persistent
symptoms attributed to Lyme borreliosis (PLEASE). Secondary objectives are:
- to assess differences in long-term outcome between the three treatment groups
of PLEASE;
- to investigate the potential relationship between pre-treatment severity and
duration of complaints, and long-term outcomes;
- to investigate the long-term impact of persistent symptoms attributed to Lyme
borreliosis on societal status and ability to work;
- to collect data on the additional medical or complementary care,
interventions and/or support that patients have undergone after participation
in PLEASE, and to correlate these data with their course of symptoms, quality
of life and ability to work;
- to assess the role self-management of patients as determinant for long-term
outcomes and ability to work;
- to assess predictors for the long-term course of complaints and workability;
- to explore a diagnostic decision model, based on the determinants for
long-term outcome, including patient characteristics, self-management, outcome
expectations and interventions, to guide future individual patient management;
and
- to obtain blood and urine samples to investigate the role of immunological
and metabolic parameters in persistent symptoms and long-term outcomes.

This is an observational cohort study, in an existing cohort of 280
participants who previously (between 5 and 8 years ago) participated in the
PLEASE trial. Participants will be subjected to extensive questionnaires once
and will be asked to collect blood and urine samples once. A randomly composed
group of patients will be interviewed. Furthermore, focus groups will be
organised for subgroups of patients with an intervention or self management
strategy that is identified as determinant for beneficial long-term outcomes
after analyses.

PLEASE5+ participants will be subjected to a comprehensive (online)
questionnaire. Blood and urine will be collected once. A subgroup of patients,
after providing additional consent, will be interviewed about their experiences
related to work, medical and social care, social relationships, and
self-management in relation to their persistent symptoms and long-term
outcomes. If intervention methods undergone by participants are identified that
are associated with beneficial effects, patients will be invited to participate
in focus groups related to those specific therapies.
There are no direct benefits for individual participants. The burden and risk
of venous blood collection is low. No other risks are expected.