UK Experts Outline Practical Ways to Manage Wearing-off in Parkinson’s

A panel of United Kingdom-based experts has defined a set of practical considerations to manage motor fluctuations and wearing-off in Parkinson’s disease patients.

Based on practical clinical experience, the guidelines were outlined in “Noninvasive options for ‘wearing-off’ in Parkinson’s disease: a clinical consensus from a panel of UK Parkinson’s disease specialists,” published in the journal Neurodegenerative Disease Management.

Currently, the gold standard therapy for Parkinson’s disease is L-Dopa (levopoda), which eases patients’ symptoms by increasing the production of dopamine, a chemical messenger involved in regulating movement and emotional response, which is reduced in Parkinson’s patients.

However, long-term use of L-Dopa can cause wearing-off symptoms — when the effects of levodopa diminish before the next dose is due — such as motor fluctuations and non-motor symptoms, as well as dyskinesia, which is abnormal, uncontrolled, involuntary movement that affects patients’ quality of life.

These symptoms also can be caused by high doses of L-Dopa, which may be necessary in advanced Parkinson’s disease.

According to a previous study, wearing-off symptoms are experienced by 63.0-75.6% of Parkinson’s patients at 1-2 years of L-dopa therapy, by 55.1-66.3% patients at 3-5 years, and by 76.8-80.4% patients after 10 years.

So, to prevent motor fluctuation without worsening dyskinesia, many Parkinson’s patients eventually require add-on therapies.

Recently, two add-on therapies for patients with Parkinson’s disease and motor fluctuations have been approved in the U.K.:  Ongentys (opicapone), which blocks the enzyme that breaks down L-Dopa, and Xadago (safinamide), which increases the level and function of dopamine.

Despite recent guidelines of the National Institute for Health and Care Excellence (NICE), decisions regarding the type of therapy, whether it should be single or combination therapy, and when and in what order to prescribe these treatments, are made between the physician and the patient.

These decisions, including when new add-on therapies should be prescribed, require the opinion of experts based on practical clinical experience.

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To complement existing guidelines, a multidisciplinary panel of eight UK-based Parkison’s and movement disorder specialists defined practical considerations — including a clinical insight in Ongentys and Xadago add-on treatment options — to manage wearing-off symptoms in Parkinson’s patients.

The clinical consensus was based on the practical experience of the panel of experts, which included neurologists and geriatricians specialized in medical care for the elderly, and a nurse specialist, from England, Scotland, and Wales.

Before a physician adjusts L-Dopa therapy or adds another class of therapy to the regimen, the panel of experts recommends the analysis of a number of factors that can directly impact the wearing-off, such as therapy compliance, gastrointestinal absorption, and diet.

Non-motor symptoms, including anxiety, apathy, depression, cognitive impairment, dizziness or fainting when moving from a sitting position to an upright position, sleep disturbances, and pain also can influence overall function in Parkinson’s patients, and must be appropriately investigated and managed.

When considering therapy adjustments or additions, a physician should weigh the benefits of adjusting L-Dopa therapy — which usually leads only to variable and short-term improvements — versus the addition of an add-on therapy to the regimen.

“The decision regarding which adjunctive therapy to use or not to use, requires considerable clinical experience from the treating clinician,” the authors wrote.

In their opinion, switching from other add-on therapies to Ongentys or Xadago is a good option for patients experiencing punctual loss of L-dopa dose clinical effects, and for those who have persistent wearing-off symptoms or worsening of dyskinesia with other add-on therapies.

The authors noted that additional studies are necessary to understand the therapeutic effects of Ongentys and Xadago in early-disease treatment, to evaluate their use along with deep-brain stimulation, and to develop a routine genetic testing of Parkinson’s patients to predict Ongentys’ response.