Continuous, subcutaneous apomorphine infusion for Parkinson disease motor fluctuations: Results from the phase 3, long-term, open-label United States InfusON study
- PMID: 39973510
- DOI: 10.1177/1877718X241310727
Continuous, subcutaneous apomorphine infusion for Parkinson disease motor fluctuations: Results from the phase 3, long-term, open-label United States InfusON study
Abstract
BackgroundContinuous subcutaneous apomorphine infusion (CSAI) has been used globally since the 1980s for Parkinson disease (PD) motor fluctuations but has not been available in the United States (US).ObjectiveEvaluate CSAI for motor fluctuations in the US setting.MethodsThis open-label study (NCT02339064) enrolled patients with PD experiencing ≥3 hours (h) daily OFF time despite optimized levodopa and current/prior use of at least one other adjunctive therapy. CSAI was initiated with a 1-2 mg bolus followed by 1 mg/h infusion titrated to optimal efficacy and tolerability. Following titration, patients entered a 52-week maintenance period.ResultsOf 99 patients treated, 85 completed the titration period, 69 completed maintenance week 12 and 48 completed maintenance week 52. Common treatment-related adverse events included infusion site nodules and erythema, dyskinesia, nausea, and somnolence, each of which occurred more frequently during the titration period. Reduction in OFF time began at CSAI initiation and reached a mean of 3.0 ± 3.18 h/day by maintenance week 12 (primary efficacy endpoint), with a corresponding increase in Good ON time of 3.1 ± 3.35 h/day. By maintenance week 12, 68% of patients rated themselves as much or very much improved, 62% had at least a 2-h reduction in daily OFF time, and mean concomitant oral levodopa and levodopa equivalent doses (excluding CSAI) had been reduced by 198 mg/day and 283 mg/day, respectively. Improvements were maintained through week 52.ConclusionsThis study supports the clinical utility of CSAI to reduce OFF time and increase Good ON time in patients with motor fluctuations inadequately controlled with oral therapy.
Keywords: Parkinson disease; apomorphine; infusion; motor fluctuations.
Plain language summary
Continuous subcutaneous apomorphine infusion (also called CSAI) is a treatment to control OFF time (periods of poor motor control) that occurs despite ongoing use of usual Parkinson disease medications like levodopa. Apomorphine is slowly infused under the skin using a thin, flexible tube connected to a small, wearable infusion device. CSAI therapy has been widely used outside the United States for its effective control of Parkinson disease symptoms since the mid 1980s. In order to gain approval for CSAI use in the United States, a specific study conducted in United States clinics and hospitals was required. In this study, people with Parkinson disease experiencing 3 or more hours of OFF time per day were started on apomorphine infusion (CSAI) therapy. The dose of apomorphine was increased until each study participant experienced the best possible benefit while still tolerating the medication. Once this dose was identified, participants continued on this dose. The most common side effects were nodules (small bumps under the skin) and erythema (redness of the skin) at the infusion site, dyskinesia (involuntary movements), nausea, and somnolence (sleepiness). These side effects were more frequently experienced at the start of treatment when the best dose of CSAI for each participant was being identified and the participant's other PD medications were being adjusted. Soon after they started CSAI treatment, participants noticed a reduction in the amount of OFF time that they experienced each day. After 12 weeks at a stable dose of CSAI treatment, participants' OFF time had decreased by about 3 hours per day on average. At the same time, most (68%) participants said they felt their symptom control was “much improved“ or “very much improved” compared to before starting CSAI therapy. Importantly, these improvements were maintained throughout one year of treatment. These findings support the use of apomorphine infusion in the United States as an effective and safe treatment option for people with Parkinson disease that does not require surgery.
Conflict of interest statement
Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Stuart H. Isaacson, Peter LeWitt, Alberto J. Espay, Rajesh Pahwa, Pinky Agarwal, Holly A. Shill, Jennifer Hui, and Khashayar Dashtipour were investigators in the InfusON study and report fees for consultancy from Supernus Pharmaceuticals Inc and US WorldMeds, LLC. Gianpiera Ceresoli-Borroni, Andrea Formella, and Peibing Qin, are employed by Supernus Pharmaceuticals Inc. In addition, Dr Isaacson reports honoraria for CME, consultant, research grants, and/or promotional speaker on behalf of: Abbvie, Acadia, Acorda, Addex, Affiris, Alexza, Allevion, Amneal, Annovis, Aptinyx, Athira, Bial, Biogen, BlueRock, Britannia, Bukwang, Cala, Cerecor, Cerevel, CND, Eli Lilly, Enterin, Esteve, Fasikl, GE Healthcare, Global Kinetics, Inhibikase, Intra-Cellular Therapies, Ipsen, Jazz, Kyowa Kirin, Lundbeck, Medscape, Merz, Michael J. Fox Foundation, Mitsubishi Tanabe, Neuralys, Neurocrine, NeuroDerm, Neurolive, Exeltis, Novartis, ONO Pharmaceutical, Parkinson Study Group, Pharma2B, Praxis, Revance, Roche, Sage, Sanofi, Scion, Stoparkinson, Sunovion, Sun Pharma, Supernus, Teva, Theravance, Transposon, and UCB. Dr Espay has received grant support from the NIH and the Michael J Fox Foundation; personal compensation as a consultant/scientific advisory board member for NeuroDerm, Amneal, Acadia, Avion Pharmaceuticals, Acorda, Kyowa Kirin, Supernus (formerly, US WorldMeds), NeuroDiagnostics, Inc (SYNAPS Dx), and Herantis Pharma; and publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer. He cofounded REGAIN Therapeutics and is co-inventor of the patent “Compositions and methods for treatment and/or prophylaxis of proteinopathies.” He serves on the editorial boards of the Journal of Parkinson's Disease, Journal of Alzheimer's Disease, European Journal of Neurology, Movement Disorders Clinical Practice, and JAMA Neurology. Dr Pahwa serves as a consultant for Abbott, AbbVie, ACADIA, Acorda, Allevion, Amneal, Appello, Biogen, BioVie, CalaHealth, Convatec, Fasikl, Genetech, Insightec, Jazz, Keiferx, Kyowa, Lundbeck, Merz, Mitsubishi Tanabe, Neurocrine, Ono, PhotoPharmics, PSG, Reagenxbio, Sage, Sun Biopharma, Supernus, UCB. He receives research support from Abbott, AbbVie, Alexza, Amylyx, Annovis, ASK Bio, Attune, Biogen, Bluerock, Bukwang, Cerevance, Cerevel, EIP, Fasikl, GemVax, Global Kinetics, Inhibikase, Intra-cellular Therapies (ITI), Jazz, Michael J Fox Foundation, Neurocrine, NeuroDerm, ONO, Parkinson's Foundation, Praxis, Roche, Sage, Scion, Sun Pharma, Teva, Theravance, UCB. Dr Agarwal has received compensation to serve as consultant and speaker for Acadia, Acorda, Adamas, Amneal, US WorldMeds and reports research grants from the Michael J Fox Foundation, Merck, Astellas, Parkinson Study Group, CHDI Foundation, US WorldMeds, Lilly USA, Biogen Idec, Acadia Pharmaceuticals, Genentech (Roche), Prilenia Therapeutics, Sun Pharma Advanced Research Company Limited (SPARC) and Centogene AG. Dr Shill reports consultancy for Biogen, Acadia, Mitsubishi Tanabe Pharma America, Inc; honoraria for advisory boards from Kyowa Kirin Inc, Jazz Pharmaceuticals and research funding from Barrow Neurological Foundation, Impax Laboratories LLC, US World Meds, NIH, Parkinson Study Group/Biogen, Sunovion, Intec Pharma, Cala Health. Dr Hui reports consultancy for Sunovion. She has research grants from US WorldMeds, Sunovion, and Roche. Dr Dashtipour has received compensation to serve as an advisor and speaker from Allergan, Acadia, Abbvie, Acorda, Amneal, Ipsen, Lundbeck, Neurocrine, Teva and US WorldMeds.Dr Lew reports consultancy for Acorda, Supernus, Neurocrine, Kyowa, Amneal, UCB, and Global Kinetics. He has research grants from the Parkinson's Study Group, Michael J. Fox Foundation, Anenberg foundation, UCB, Jazz Pharmaceuticals, Neuraly, NIAA, Jazz Pharmaceuticals, Inhibikase Therapeutics, Biogen, Ono Pharma. Dr LeWitt has received compensation from consulting or lectures from Abide, Amneal, Biogen, Bukwang, Cavion, Denali, Hoffmann-La Roche, Jazz Pharmaceuticals, Kyowa, Mitsubishi NeuroDerm Ltd, Neurocrine, ONO Pharma USA, Revance, US WorldMeds, and Voyager Therapeutics; research grant support from Acorda Therapeutics, Biotie Therapies, Lundbeck, Merz, Michael J Fox Foundation for Parkinson's Research, Parkinson Study Group, Pharma 2B, Revance, Roche, Sunovion, Sun Pharma, and Supernus. Peter LeWitt and Alberto Espay are Editorial Board Members of this journal but were not involved in the peer-review process of this article nor had access to any information regarding its peer-review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous
