touchROUNDTABLE The impact of delayed ON: Treating OFF episodes in patients with Parkinson’s disease
Leading experts Stuart Isaacson MD, Yasar Torres-Yaghi MD, Rajesh Pahwa MD discuss how to reduce the impact of delayed ON in Parkinson’s disease
Dr Stuart Isaacson
Parkinson's Disease and Movement Disorder Center of Boca Raton, Boca Raton, FL, USA
CHAIR
Panelists:
Welcome and introduction
Dr Isaacson provides an overview of the changing response to levodopa over time and the types of OFF episodes, which patients may experience.
1/7 Next ChapterThe impact of OFF Episodes, Including Delayed ON
Dr Yasar Torres-Yaghi describes the incidence of OFF episodes, the relationship between quality of life and OFF episodes, and the contribution of delayed ON to daily OFF time based on data from various studies (including observational studies) and surveys.
2/7 Next ChapterThe current treatment approach to OFF
Dr Pahwa outlines the goals of treating OFF, the impact of existing therapies on OFF episodes, and a potential shift in treatment paradigm for OFF episodes.
3/7 Next ChapterPanel discussion: how to identify the type of OFF and select an intervention
The panel discusses how to identify which type of OFF episodes a patient is experiencing and how to select an appropriate intervention.
4/7 Next ChapterSelecting patients: Delphi Panel on the Pharmacological Approach to OFF Episodes in PD
Dr Isaacson provides an overview of the methodology and results of a Delphi panel to develop a consensus on when on-demand therapies should be considered for the treatment of OFF episodes.
5/7 Next ChapterPanel discussion: how to select patients
The panel discusses how to select patients who may benefit from on-demand therapy.
6/7 Next ChapterConclusions and close
The panel conclude discussions with the key take-home messages.
7/7 Leave FeedbackOverview & Learning Objectives
Overview
The consistent beneficial effect of each levodopa dose is reduced with Parkinson’s disease progression leading to increased frequency of cycling between ON and OFF states.1 OFF episodes can result from delayed onset of response to a levodopa dose (delayed ON).1 On-demand treatments can provide an acute conversion from OFF to ON for all types of OFF episodes, and can serve as a complementary therapy to address delayed time to ON.1–5 In this activity, leading experts provide guidance on when to use on-demand therapy and which patients may benefit.
Learning Objectives
After watching this activity, participants should be better able to:
- Outline the impact of delayed ON in the context of the total daily OFF time experienced by a patient.
- Discuss potential changes in treatment approach based on the type of OFF experienced by patients.
- Identify patients who may benefit from an on-demand therapy for OFF based on the findings of an expert consensus panel.
Faculty & Disclosures
Dr Stuart Isaacson
Parkinson's Disease and Movement Disorder Center of Boca Raton, Boca Raton, FL, USA
Dr Isaacson is a neurologist specializing in Parkinson’s disease and movement disorders, and Medical Director of the Parkinson’s Research and Education Foundation. He has been involved in over 75 clinical trials and has authored or nearly 100 journal articles, book chapters and abstracts. He has also served on national and international committees for drug development programs and trials, as well as for the Parkinson Study Group and the movement disorders section of the American Academy of Neurology.
Honoraria for CME, consultant, research grants, and/or promotional speaker on behalf of: Abbvie, Acadia, Acorda, Adamas, Addex, Affiris, Alexza, Allergan, Amarantus, Amneal, Aptinyx, Axial, Axovant, Benevolent, Bial, Biogen, Biovie, Britannia, Cadent, Cala, Cerecor, Cerevel, Cipla, Eli Lilly, Enterin, GE Healthcare, Global Kinetics, Impax, Impel, Intec Pharma, Ipsen, Jazz, Kyowa Kirin, Lundbeck, Merz, Michael J. Fox Foundation, Mitsubishi Tanabe, Neuralys, Neurocrine, Neuroderm, Novartis, Parkinson Study Group, Pharma2B, Praxis, Prilenia, Promentis, Revance, Roche, Sage, Sanofi, Scion, Stoparkinson, Sunovion, Sun Pharma, Supernus, Teva, Theravance and Transposon.
Dr Yasar Torres-Yaghi
Department of Neurology, Medstar Georgetown University Hospital, Washington D.C, USA
Dr Torres-Yaghi is an expert in movement disorders at Medstar Georgetown University Hospital. He completed a fellowship at MedStar Georgetown University Hospital in neuro-restoration research. Dr Torres-Yaghi is also leading a research initiative to care for aging patients with neurodegenerative conditions with overlapping features of both cognitive impairment and Parkinson’s disease.
Honoraria from Sunovion.
Dr Rajesh Pahwa
University of Kansas Medical Center, Movement Disorders Division, Kansas City, KS, USA
Dr Rajesh Pahwa is Professor of Neurology and Director of Parkinson Foundation Center of Excellence at the University of Kansas Medical Center. He has conducted more than 75 clinical trials related to Parkinson’s disease and other movement disorders and published more than 250 peer-reviewed articles, chapters and abstracts in leading neurology and movement disorder journals.
Consultant for Abbott, AbbVie, ACADIA, Acorda, Allevion, Amneal, Artemida, Avion, BioVie, CalaHealth, Global Kinetics, Insightec, Jazz, Kyowa, Neurocrine, Neuroderm, PhotoPharmics, Sage, Sunovion, Supernus, UCB and Wren. Research support from Abbott, AbbVie, Addex, Biogen, Biohaven, Boston Scientific, EIP, Global Kinetics, Impax, Intec, Lilly, Neuroderm, Neuraly, Parkinson’s Foundation, Pharma 2B, Prelinia, Roche, Sage, SIS, Sun Pharma, Sunovion, Theranexus, Theravance, and Voyager.
References
- Vijiaratnam N, Foltynie T. Therapeutic Strategies to Treat or Prevent Off Episodes in Adults with Parkinson's Disease. Drugs 2020; 80(8): 775-96.
- Hauser RA, LeWitt PA, Comella CL. On demand therapy for Parkinson's disease patients: Opportunities and choices. Postgrad Med 2021; 133(7): 721-7.
- Hui JS, Fox SH, Neeson W, et al. Open-label titration of apomorphine sublingual film in patients with Parkinson's disease and "OFF" episodes. Parkinsonism Relat Disord 2020; 79: 110-6.
- Olanow CW, Factor SA, Espay AJ, et al. Apomorphine sublingual film for off episodes in Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 study. Lancet Neurol 2020; 19(2): 135-44.
- Isaacson S. Use of on-demand treatments for off episodes in parkison’s disease: guidance from a rand/ucla modified delphi consensus panel. 4th Pan American Parkinson’s Disease and Movement Disorders Congress (PAS); 2022 May 26-28, 2022; Miami, USA; 2022.
- Armstrong MJ and Okun MS. Diagnosis and Treatment of Parkinson Disease: A Review. JAMA. 2020;323:548-560.
- Adler CH. Relevance of motor complications in Parkinson's disease. Neurology. 2002;58(4 suppl 1):S51-S56.
- Ahlskog JE, Muenter MD. Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov Disord. 2001;16(3):448-458.
- Chou KL, Stacy M, Simuni T, et al. The spectrum of "off" in Parkinson's disease: What have we learned over 40 years? Parkinsonism Relat Disord. 2018;51:9-16.
- Chapuis S, Ouchchane L, Metz O, et al. Impact of the motor complications of Parkinson's disease on the quality of life. Mov Disord. 2005;20:224-230.
- Elmer LW, Juncos JL, Singer C, et al. Pooled Analyses of Phase III Studies of ADS-5102 (Amantadine) Extended-Release Capsules for Dyskinesia in Parkinson's Disease. CNS Drugs. 2018;32:387-398.
- Fasano A, Visanji NP, Liu LW, et al. Gastrointestinal dysfunction in Parkinson's disease. Lancet Neurol. 2015;14:625-639.
- Ferreira JJ, Lees A, Rocha JF, et al. Opicapone as an adjunct to levodopa in patients with Parkinson's disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial. Lancet Neurol. 2016;15:154-165.
- Fox SH, Katzenschlager R, Lim SY, et al. International Parkinson and movement disorder society evidence-based medicine review: Update on treatments for the motor symptoms of Parkinson's disease. Mov Disord. 2018;33:1248-1266.
- Hauser RA Isaacson SH, Ellenbogen A, et al. Orally inhaled levodopa (CVT-301) for early morning OFF periods in Parkinson's disease. Parkinsonism Relat Disord. 2019;64:175-180.
- Hui JS, Fox SH, Neeson W, et al. Open-label titration of apomorphine sublingual film in patients with Parkinson's disease and "OFF" episodes. Parkinsonism Relat Disord. 2020;79:110-116.
- Isaacson S, Lew M, Ondo W, et al. Apomorphine Subcutaneous Injection for the Management of Morning Akinesia in Parkinson's Disease. Mov Disord Clin Pract. 2017;4:78-83.
- Isaacson SH, Pahwa R, Pappert EJ, et al. Should "on-demand" treatments for Parkinson's disease OFF episodes be used earlier? Clin Park Relat Disord. 2022;6:100145.
- Isaacson SH, Achari M, Bhidayasiri R, et al. Use of on-demand treatments for OFF episodes in Parkinson’s disease: guidance from a RAND/UCLA modified Delphi consensus panel. Presented at: 4th Pan American Parkinson’s Disease and Movement Disorder Congress (PAS); May 26-28, 2022; Miami, FL USA. Poster 123.
- Leenders KL, Poewe WH, Palmer AJ, et al. Inhibition of L-[18F]fluorodopa uptake into human brain by amino acids demonstrated by positron emission tomography. Ann Neurol. 1986;20:258-262.
- LeWitt PA, Guttman M, Tetrud JW, et al. Adenosine A2A receptor antagonist istradefylline (KW-6002) reduces "off" time in Parkinson's disease: a double-blind, randomized, multicenter clinical trial (6002-US-005). Ann Neurol. 2008;63:295-302.
- Lieberman A, Ranhosky A, Korts D. Clinical evaluation of pramipexole in advanced Parkinson's disease: results of a double-blind, placebo-controlled, parallel-group study. Neurology. 1997;49:162-168.
- Magrinelli F, Picelli A, Tocco P, et al. Pathophysiology of Motor Dysfunction in Parkinson's Disease as the Rationale for Drug Treatment and Rehabilitation. Parkinsons Dis. 2016:9832839.
- Merims D, Djaldetti R, Melamed E. Waiting for ON: a major problem in patients with Parkinson disease and ON/OFF motor fluctuations. Clin Neuropharmacol. 2003;26:196-198.
- Müller T, Erdmann C, Bremen D, et al. Impact of gastric emptying on levodopa pharmacokinetics in Parkinson disease patients. Clin Neuropharmacol. 2006;29:61-67.
- Nijhuis FAP, van den Heuvel L, Bloem BR, et al. The Patient's Perspective on Shared Decision-Making in Advanced Parkinson's Disease: A Cross-Sectional Survey Study. Front Neurol. 2019;10:896.
- Obeso JA, Rodriguez-Oroz MC, Chana P, et al. The evolution and origin of motor complications in Parkinson's disease. Neurology. 2000;55(suppl 4):S13-S20.
- Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009;72(21 suppl 4):S1-S136.
- Olanow CW, Poewe W, Rascol O, et al. On-Demand Therapy for OFF Episodes in Parkinson's Disease. Mov Disord. 2021;36:2244-2253.
- Pahwa R, Stacy MA, Factor SA, et al. Ropinirole 24-hour prolonged release: randomized, controlled study in advanced Parkinson disease. Neurology. 2007;68:1108-1115.
- Rascol O, Brooks DJ, Melamed E, et al. Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial. Lancet. 2005;365:947-954.
- Rajput AH, Martin W, Saint-Hilaire MH, et al. Tolcapone improves motor function in parkinsonian patients with the "wearing-off" phenomenon: a double-blind, placebo-controlled, multicenter trial. Neurology. 1997;49:1066-1071.
- Reimer J, Grabowski M, Lindvall O, et al. Use and interpretation of on/off diaries in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2004;75:396-400.
- Rinne UK, Larsen JP, Siden A, et al. Entacapone enhances the response to levodopa in parkinsonian patients with motor fluctuations. Nomecomt Study Group. Neurology. 1998;51:1309-1314.
- Stocchi F, Coletti C, Bonassi S, et al. Early-morning OFF and levodopa dose failures in patients with Parkinson's disease attending a routine clinical appointment using Time-to-ON Questionnaire. Eur J Neurol. 2019;26:821-826.
- Suttrup I, Suttrup J, Suntrup-Krueger S, et al. Esophageal dysfunction in different stages of Parkinson's disease. Neurogastroenterol Motil. 2017;29(1).
- Tan AH, Mahadeva S, Thalha AM, et al. Small intestinal bacterial overgrowth in Parkinson's disease. Parkinsonism Relat Disord. 2014;20:535-540.
- Thach A, Jones E, Pappert E, et al. Real-world assessment of the impact of "OFF" episodes on health-related quality of life among patients with Parkinson's disease in the United States. BMC Neurol. 2021;21:46.
- Thach A, Zichlin M, Peddle M, et al. Systematic literature review of key outcomes used to assess adjunctive treatments for Parkinson’s disease. Presented at: International Parkinson’s Disease and Movement Disorder Society Congress (MDS); 15–18 September, 2022; Madrid, Spain. Poster 783.
