Accreditation/Credit Designation

Physicians' Education Resource®, LLC is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Physicians' Education Resource®, LLC designates this live activity for a maximum of 1.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Physicians' Education Resource®, LLC is approved by the California Board of Registered Nursing, Provider #16669 for 1.5 Contact Hour.

Acknowledgment of Commercial Support

This activity is supported by educational grants from by Acorda Therapeutics, Inc, and Neurocrine Biosciences, Inc.

Medical Crossfire®: Managing Motor Fluctuations And Dyskinesia In Parkinson's Disease: Turning The “Off” Switch “On”

Release Date: November 30, 2018
Expiration Date: November 30, 2019
Media: Internet - based

Activity Overview

Parkinson's disease (PD) is the second most common neurogenerative disease after Alzheimer’s disease, affecting approximately 1 million people in the United States. The progression of PD and degree of impairment vary by individual and include impaired motor function, bradykinesia, tremor, gait and balance disturbances, and nonmotor symptoms such as sleep disorders, neuropsychiatric disturbances, gastrointestinal symptoms, and sensory deficits. The gold standard for management of motor symptoms is levodopa, the metabolic precursor of dopamine. However, levodopa has a short half-life and is poorly absorbed by some patients, leading to motor fluctuations and dyskinesia in long-term treatment of patients with PD. Approximately 10% of patients per year develop motor fluctuations after initiating levodopa, and 50% of patients with PD will develop these complications after 5 years of treatment. Dyskinesia typically follows motor fluctuations and is commonly associated with levodopa. The time when pharmacologic therapies are providing patient benefits in treating PD motor symptoms is referred to as “on” time. Conversely, the time when these therapies are not providing motor benefits is referred to as “off” time. Adequate management of off time remains one of the major unmet needs of PD management, and emerging treatments can provide effective and convenient relief.

During this Medical Crossfire®, a panel of expert faculty will review evidence-based therapeutic options for the management of motor fluctuations and dyskinesia in PD and discuss new and emerging levodopa and non-levodopa-based therapies. The panel will also discuss the importance of developing a patient-centered approach to care and strategies to effectively engage a multidisciplinary team to improve the management of PD motor fluctuations during off periods.

Acknowledgment of Commercial Support

This activity is supported by educational grants from by Acorda Therapeutics, Inc, and Neurocrine Biosciences, Inc.

Instructions for This Activity and Receiving Credit

  • You will need to login to participate in the activity.
  • Each presentation may contain an interactive question(s). You may move forward through the presentation; however, you may not go back to change answers or review videos/content until you finish the presentation.
  • At the end of the activity, “educational content/video files” will be available for your reference.
  • In order to receive a CME/CE certificate, participants must complete the activity.
  • Complete the posttest and pass with a score of 70% or higher, complete the evaluation and then click on request for credit. Participants may immediately download a CME/CE certificate upon completion of these steps.


Target Audience

This continuing medical education (CME) activity is intended for neurologists, nurse practitioners (NPs), physician assistants (PAs), and other health care professionals involved in the treatment and management of patients with PD.

Educational Objectives

Upon successful completion of this educational program, you should be better prepared to:

  1. Review evidence-based pharmacologic treatment options for management of motor fluctuations and dyskinesia in PD.
  2. Review new and emerging treatments for motor fluctuations and dyskinesia in PD.
  3. Discuss ways to add midlevel providers to the PD treatment team.

Faculty, Staff, and Planners' Disclosure

Faculty

Paul P. Doghramji, MD, FAAFP
Paul P. Doghramji, MD, FAAFP
Family Physician, Collegeville Family Practice
Medical Director, Health Services, Ursinus College
Collegeville, Pennsylvania
 

Disclosure: No financial information to disclose.

Peter A. LeWitt, MD
Peter A. LeWitt, MD
Director Parkinson Disease and Movement Disorder Program
Henry Ford Hospital
West Bloomfield, Michigan
 

Disclosures: Grant/research support: Acorda Therapeutics, Adamas, Biotie Therapies, Lundbeck, The Michael J. Fox Foundation for Parkinson’s Research, Parkinson Study Group, Pharma Two B, Revance, Roche, Sunovion, US WorldMeds; Consultant: Abide Therapeutics, Acorda Therapeutics, Biogen, Britannia Pharmaceuticals, Cavion, Denali Therapeutics; Intec Pharma, Jazz Pharmaceuticals, Lundbeck, Neurocrine Biosciences, NeuroDerm, Prexton Therapeutics, Revance, Sage Therapeutics, SynAgile, Titan Pharmaceuticals, US WorldMeds; Other support: annual stipend as editor-in-chief of Clinical Neuropharmacology

Corneliu Luca, MD
Corneliu Luca, MD
Associate Professor of Neurology
University of Miami
Miami, Florida
 

Disclosures: Grant/research support: Medtronic, National Institutes of Health, Parkinson’s Foundation; Consultant: Abbott, Abbvie, Medtronic

Cathi A. Thomas, MS, RN, CNRN
Cathi A. Thomas, MS, RN, CNRN
Assistant Clinical Professor of Neurology
Program Director, Parkinson Disease and Movement Disorders Center
Boston University Medical Campus
Boston, Massachusetts
 

Disclosures: Consultant: Acorda Therapeutics, Allied Health Professionals Medical Advisory Board meeting, Delsys

The staff of Physicians’ Education Resource®, LLC have no relevant financial relationships with commercial interests to disclose.

Disclosure Policy and Resolution of Conflicts of Interest

As a sponsor accredited by the ACCME, it is the policy of PER® to ensure fair balance, independence, objectivity, and scientific rigor in all of its CME activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME/CE activity to disclose all relevant financial relationships with commercial interests. The ACCME defines “relevant financial relationships” as financial relationships in any amount occurring within the past 12 months that creates a COI.
 
Additionally, PER® is required by ACCME to resolve all COI. PER® has identified and resolved all COI prior to the start of this activity by using a multistep process.

Off-Label Disclosure and Disclaimer

This CME/CE activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME/CE activity is for continuing medical and nursing education purposes only, and is not meant to substitute for the independent clinical judgment of a physician or nurse relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER®.

PER Pulse™ Recaps

1 of 3

The online continuing medical education (CME) activity Managing Motor Fluctuations and Dyskinesia in Parkinson Disease: Turning the “Off” Switch “On,” features a roundtable discussion that unveils the challenges of consistent treatment delivery to afford patients motor control throughout the day. Paul Doghramji, MD, moderates a discussion between expert faculty Peter LeWitt, MD; Corneliu Luca, MD, PhD; and Cathi Thomas, MS, RN, CNRN, to provide perspectives on how to best optimize and individualize management for the off episodes in patients with Parkinson disease with current medications and with insight on evolving treatments.
 
This first of 3 PER Pulse™ Recaps will focus on the need for individualized treatment with current medications and strategies for managing off periods, as explored in Managing Motor Fluctuations and Dyskinesia in Parkinson Disease: Turning the “Off” Switch “On.
 
Levodopa has been the cornerstone of Parkinson disease treatment for more than 50 years, but it exhibits considerable variability in patients over time. After 3 or more years of treatment, a patient may experience substantial off time associated with undermedication, unreliability, delay in onset of effect and subsequent adjustments to lifestyle because of the unpredictability. For some patients, different combinations of treatments are needed for the best level of control, but there is still considerable variability in responses. Treatment adherence is another challenge as some patients require medication 5 to 6 times a day to manage motor fluctuations.
 
A common strategy is to start patients on a low dose of carbidopa-levodopa for as long as possible and to add adjunctive therapies and/or decrease the carbidopa-levodopa when motor fluctuations become troublesome. Half of patients will eventually need a medication other then carbidopa-levodopa.
 
Although the gold standard of carbidopa-levodopa is an immediate-release form with a half-life of 2.5 to 3.0 hours, options for optimal motor control include sustained-release and extended-release carbidopa-levodopa. A triple combination with the addition of entacapone is also available. Entacapone is a catechol-O-methyltransferase enzyme inhibitor that has been proven to increase bioavailability of levodopa by extending its half-life.1 In severe situations when motor fluctuations are not manageable with oral therapies, intrajejunal infusion of levodopa gel provides a steady state of treatment which increases “on’ time without dyskinesia.
 
Key Points
  • Long-term use of levodopa can lead to motor fluctuations, requiring adjunctive treatments

  • Different formulations of carbidopa-levodopa allow for treatment individualization

  • Eventually about half of patients with Parkinson disease will need an alternative to carbidopa-levodopa

Reference    
 
  1. Ray Chaudhuri K, Qamar MA, Rajah T, et al. Non-oral dopaminergic therapies for Parkinson disease: current treatments and the future. NPJ Parkinson Dis. 2016;2:16023. doi: 10.1038/npjparkd.2016.23.


2 of 3

As a follow-up to the online CME activity Managing Motor Fluctuations and Dyskinesia in Parkinson Disease: Turning the “Off” Switch “On,” this second of 3 PER Pulse™ Recaps for the activity will focus on new and emerging treatments for management of motor fluctuation in Parkinson disease.
 
A number of levodopa and nonlevodopa treatments, both nonoral and device-aided, are recently approved or under investigation to extend symptom control when needed and improve patient quality of life while overcoming the challenges of absorption with oral levodopa. Poor absorption of levodopa could be the main cause of many levodopa-induced motor fluctuations1 concomitantly with the relatively small area of the proximal jejunum where levodopa is absorbed. In addition, levodopa is not absorbed in the mouth; an orally dissolving or sublingual therapy will not be effective. Some patients may also have difficulty swallowing pills.
 
Levodopa-based therapies:
Inhaled levodopa (CVT-301)
CVT-301 is a recently FDA-approved self-administered dry powder aerosol containing levodopa as a “rescue therapy”. Pulmonary absorption gives instant dispersion of levodopa to the absorptive membrane, thus avoiding the variability in gastrointestinal (GI) absorption while providing improved pharmacokinetics and dosing reliability.2
 
Liquid levodopa-carbidopa (ND0612)
ND06012 is a liquid formulation of levodopa/carbidopa for subcutaneous, continuous delivery via a belt or transdermal patch pump for moderate to severe Parkinson disease.3
 
Intrajejunal levodopa infusion 
Levodopa-carbidopa-entacapone intrajejunal infusion is an intestinal gel that is administered continuously into the proximal jejunum via a percutaneous endoscopic gastrojejunostomy tube connected to a portable infusion pump.4
 
Non–Levodopa-based therapies:
Apomorphine infusions
These infusions are supported by evidence for use in controlling motor fluctuations in patients with advanced Parkinson disease and may be helpful earlier in the disease to prevent dyskinesia.5
 
Inhaled apomorphine (VR040)
VR040 is a dry powder apomorphine formulation delivered through the pulmonary system to quickly alleviate symptoms in “off” times.6
 
Sublingual apomorphine (APL-130277)
APL-130277 is a thin-film strip in sublingual form for absorption through the oral cavity mucosa, allowing rapid delivery independent of the GI system. It has been shown to be effective in rapid conversion to the “on” stage, regardless of Parkinson disease severity.7
 
Subcutaneous rotigotine (RTG) polyoxazoline (SER-214)
Polyoxazolines (POZs) are biodegradable biconjugate polymers with potential in drug delivery. A POZ-RTG conjugate, delivered subcutaneously, aims to provide continuous dopaminergic stimulation, with greater control on drug loading and rate of release.8
 
Safinamide
Safinamide is a recently FDA-approved add-on treatment dosed in 50- or 100-mg tablets for patients with Parkinson disease currently taking levodopa-carbidopa to control “off” time.
 
Key Points

  • Poor absorption of levodopa may be the cause of motor fluctuations

  • New and emerging levodopa-based treatments can overcome poor GI absorption with nonoral or device delivery

  • New and emerging nonlevodopa treatments include oral, sublingual, and subcutaneous infusions


References
 

  1. Ray Chaudhuri K, Qamar MA, Rajah T, et al. Non-oral dopaminergic therapies for Parkinson disease: current treatments and the future. NPJ Parkinson Dis. 2016;2:16023. doi: 10.1038/npjparkd.2016.23.
  2. LeWitt PA, Hauser RA, Pahwa R, et al; SPAN-PD Study Investigators. Safety and efficacy of CVT-301 (levodopa inhalation powder) on motor function during off periods in patients with Parkinson disease: a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Neurol. 2019;18(2):145-154. doi: 10.1016/S1474-4422(18)30405-8.
  3. A Clinical Study Investigating the Efficacy, Tolerability, and Safety of Continuous Subcutaneous ND0612 Infusion Given as Adjunct Treatment to Oral Levodopa in Patients With Parkinson Disease With Motor Fluctuations. clinicaltrials.gov/ct2/show/NCT02782481. Updated November 22, 2018. Accessed January 28, 2019.
  4. A Study to Compare Plasma Levels of Levodopa, Carbidopa and Entacapone After TRIGEL or Duodopa Infusion in PD Patients. clinicaltrials.gov/ct2/show/NCT02448914. Updated Mary 23, 2016. Accessed January 28, 2019.
  5. Antonini A, Jenner P. Apomorphine infusion in advanced Parkinson disease. Nat Rev Neurol. 2018;14(12):693-694. doi: 10.1038/s41582-018-0083-y.
  6. Phase IIa Multicentre Study Investigating of VR040 in Parkinson Disease (VR040/2/003). clinicaltrials.gov/ct2/show/NCT01693081. Updated September 26, 2012. Accessed January 28, 2019.
  7. An Open-Label Phase 3 Study to Examine the Long-Term Safety, Tolerability and Efficacy of APL-130277 for the Acute Treatment of "OFF" Episodes in Patients With Parkinson Disease. clinicaltrials.gov/ct2/show/NCT02542696. Updated March 22, 2018. Accessed January 28, 2019.
  8. A Study of Weekly Subcutaneous Injections of SER-214 in Subjects With Parkinson Disease (PD), to Determine the Safety, Tolerability and Pharmacokinetic (PK) Profile of SER-214. clinicaltrials.gov/ct2/show/NCT02579473. Updated September 5, 2018. Accessed January 28, 2019.
  9. FDA approves drug to treat Parkinson disease [news release]. Silver Spring, MD: FDA; March 21, 2017. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm547852.htm. Accessed January 28, 2019.

3 of 3

As a follow-up to the online CME activity, Managing Motor Fluctuations and Dyskinesia in Parkinson Disease: Turning the “Off” Switch “On,” this third of 3 PER Pulse™ Recaps for the activity will focus on a team-based approach to improve the management of patients with Parkinson disease.
Patients with Parkinson disease typically receive their diagnosis with 10 to 20 years of life ahead of them. A team-based approach can both improve outcomes and a patient’s quality of life. With the primary care physician orchestrating the patient’s care, referrals to a neurologist and a movement disorder specialist are generally made when the diagnosis is suspected. Additional MD specialists on the team may include urologists and gastroenterologists.
 
Advanced-practice clinicians, including nurse practitioners or physician assistants, may specialize in Parkinson care and are instrumental in the patient’s overall healthcare, from primary care maintenance, management of comorbidities, communication with other team members, and patient/caregiver education to providing community resources. Rehabilitation specialists are also a very important part of a person's care, right from diagnosis. At the time of their diagnosis, patients already have some disability, whether it is in speech or having low voice volume or motor disability. Specific exercises that improve balance and flexibility, and gait-specific training,1 are more important than a cardio workout. Evidence also supports psychosocial benefits of group exercise.2
 
Patients undergoing significant changes may require admission to rehabilitation hospitals for careful monitoring of medications and interventions that may help avoid an acute hospitalization. Longer rehabilitation in a skilled nursing facility may be necessary for some patients.
 
Key Points

  • A multidisciplinary approach to patients with Parkinson disease will improve quality of life and outcomes by addressing the patient’s primary and diverse care needs

  • Exercise therapy is highly recommended in the early stages of Parkinson disease

  • Patient care for Parkinson disease spans all healthcare settings

 
References

  1. Ni M, Hazzard JB, Signorile JF, Luca C. Exercise guidelines for gait function in Parkinson disease: a systematic review and meta-analysis. Neurorehabil Neural Repair. 2018;32(10):872-886. doi: 10.1177/1545968318801558.
  2. Claesson IM, Stahle A, Johansson S. Wiseman T. Being limited by Parkinson disease and struggling to keep up exercising; is the group the glue? Disabil Rehabil. 2019;1-5. doi: 10.1080/09638288.2018.1522552.

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