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Review
. 2022 Aug 12:7:100161.
doi: 10.1016/j.prdoa.2022.100161. eCollection 2022.

Should "on-demand" treatments for Parkinson's disease OFF episodes be used earlier?

Stuart H Isaacson  1 , Fernando L Pagan  2 , Mark F Lew  3 , Rajesh Pahwa  4
Affiliations
Review

Should "on-demand" treatments for Parkinson's disease OFF episodes be used earlier?

Stuart H Isaacson et al. Clin Park Relat Disord. .

Abstract

We discuss a shift in the treatment paradigm for OFF episode management in patients with Parkinson's disease, based on clinical experience in the United States (US). Three "on-demand" treatments are currently available in the US as follows: subcutaneous apomorphine, levodopa inhalation powder, and sublingual apomorphine. We empirically propose that "on-demand" treatments can be utilized as a complementary treatment when OFF episodes emerge and can be utilized when needed rather than reserving these treatments only until other treatment approaches (adjustment of baseline treatment and/or addition of adjunctive treatment with "ON-extenders") have failed. Current treatment approaches combine "ON-extenders" with increasing levodopa dosing and/or frequency to treat OFF episodes. Yet, OFF episodes often persist, with a substantial amount of daily OFF time. OFF episode treatment is hindered by variable gastrointestinal (GI) absorption of oral levodopa, reflecting GI dysmotility and protein competition. Novel "on-demand" treatments bypass the gut and can improve OFF symptoms more rapidly and reliably than oral levodopa. With the emergence of novel "on-demand" treatments, we conclude that a shift in treatment paradigm to the earlier, complementary use of these medications be considered.

Keywords: Apomorphine hydrochloride injection; Apomorphine sublingual film; Levodopa inhalation powder; Motor fluctuations; Rescue therapy.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SHI reports honoraria for CME, consultant, research grants, and/or promotional speaker on behalf of AbbVie, Acadia Pharmaceuticals Inc., Acorda Therapeutics, Inc., Adamas Pharmaceuticals, Inc., Addex Therapeutics, AFFiRiS AG, Alexza Pharmaceuticals, Allergan, Amneal Pharmaceuticals LLC, Aptinyx Inc., Axial Therapeutics, Inc., Benevolent, Biogen, Biovie, Britannia Pharmaceuticals Ltd, Cadent Therapeutics, Cala Health, Cerecor Inc., Cerevel Therapeutics, Eli Lilly, Enterin Inc., GE Healthcare, Global Kinetics Pty Ltd, Impax Laboratories, Impel NeuroPharma, Intec Pharma, Jazz Pharmaceuticals, Kyowa Kirin, Lundbeck, Merz Pharmaceuticals, Michael J. Fox Foundation, Neuralys Inc, Neurocrine Biosciences, Inc., Neuroderm, Novartis, Parkinson Study Group, Pharma Two B Ltd., Praxis, Prilenia Therapeutics, Revance, Roche, Sage, Sanofi, Scion, Scion Neurostim, Stoparkinson, Sunovion Pharmaceuticals Inc., Sun Pharma, Supernus Pharmaceuticals, Inc., Teva Pharmaceuticals, Theravance Biopharma, Transposon, and UCB. FLP reports fees for consulting or speaker services from AbbVie, Acorda Therapeutics, Inc., Adamas Pharmaceuticals, Inc., Amneal Pharmaceuticals LLC, Kyowa Kirin, Merz Pharmaceuticals, LLC, Neurocrine Biosciences, Sunovion Pharmaceuticals Inc., Supernus Pharmaceuticals, Inc., Teva Pharmaceuticals, and US WorldMeds. He has received stock or has an ownership interest in KeifeRx and has received research support from Novartis and US WorldMeds. MFL reports consultant or speaker services from Acadia, Acorda Therapeutics, Adamas, Kyowa, Neurocrine, and Supernus Pharmaceuticals, Inc., and is an active researcher for Michael J. Fox Foundation, Neuraly Inc, NIAA, Parkinson Study Group, Pharma Two B Ltd., and Sun Pharma. RP reports honoraria, consultant fees, and/or research grants from Abbott Laboratories, AbbVie, Acadia Pharmaceuticals Inc., Acorda Therapeutics, Inc., Adamas Pharmaceuticals, Inc., Amneal Pharmaceuticals LLC, Biogen, Biohaven Pharmaceuticals Inc., Boston Scientific, Cala Health, EIP Pharma, Inc., Eli Lilly, Global Kinetics Pty Ltd, Kyowa Kirin, Lundbeck, Mitsubishi Tanabe Pharma America, Neuraly Inc., Neurocrine Biosciences, Parkinson Foundation, Pharma Two B Ltd., Prilenia Therapeutics, Roche, Sage Therapeutics, Sun Pharma, Sunovion Pharmaceuticals Inc., Theranexus, Theravance Biopharma, US WorldMeds LLC, and Voyager.

Figures

Fig. 1
Fig. 1
Two pharmacologic approaches to manage OFF episodes in patients with PD. (A, Conventional Approach; B, Treatment Paradigm Shift) PD, Parkinson’s disease.
See this image and copyright information in PMC

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