Clinically important change on the Unified Dyskinesia Rating Scale among patients with Parkinson's disease experiencing dyskinesia.

Background

The Unified Dyskinesia Rating Scale (UDysRS) evaluates dyskinesia in patients with Parkinson's disease (PD). A minimal clinically important change (MCIC)-the smallest change in a treatment outcome that a patient considers important-remains undefined for the UDysRS.

Objective

To utilize pivotal amantadine delayed-release/extended-release (DR/ER) trial data to derive MCICs for the UDysRS total score in patients with PD experiencing dyskinesia.

Methods

Pivotal trials included PD patients with ≥1 h daily ON time with troublesome dyskinesia and baseline scores ≥2 on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV, item 4.2. Patients randomized to amantadine DR/ER or placebo completed two consecutive 24-h diaries before each clinic visit and were evaluated during ON time with dyskinesia using the UDysRS, MDS-UPDRS, and Clinician Global Impression of Change (CGI-C). The UDysRS changes from baseline to week 12 were anchored to corresponding changes in MDS-UPDRS item 4.2 scores. A minimal clinically important improvement in the CGI-C and diary-reported ON time with troublesome dyskinesia (≥0.5 h) were supportive anchors. Receiver operating characteristic curves determined the UDysRS change values optimizing sensitivity and specificity to at least minimal improvement on each anchor.

Results

The analyses included 196 patients. Week 12 UDysRS total score reduction of ≥8 points corresponded to at least minimal MDS-UPDRS item 4.2 improvement. UDysRS reduction of ≥9 points corresponded to decreased ON time with troublesome dyskinesia of ≥0.5 h per patient diaries, and UDysRS reduction of ≥10 points corresponded to at least minimal improvement on the CGI-C.

Conclusion

Anchored to the MDS-UPDRS Part IV, item 4.2, an 8-point reduction in the UDysRS total score can be considered an MCIC for PD patients with dyskinesia.

Informations de copyright

Copyright © 2022 Pahwa, Fox, Hauser, Isaacson, Lytle, Johnson, Llorens, Formella and Tanner.

Déclaration de conflit d'intérêts

Author RP reports consulting fees from AbbVie, ACADIA Pharmaceuticals, Acorda Therapeutics, Adamas Pharmaceuticals, Cynapsus Therapeutics, Global Kinetics, Ionis Pharmaceuticals, Lundbeck, Neurocrine Biosciences, St. Jude Medical, Teva Neuroscience, UCB, and US WorldMeds; and research grants from Acorda Therapeutics, Adamas Pharmaceuticals, Avid Radiopharmaceuticals, Boston Scientific, Cala Health, Cynapsus Therapeutics, Kyowa, National Parkinson's Foundation, NIH/NINDS, Parkinson's Study Group, Pfizer, and US WorldMeds. Author SF reports consultant fees from Sunovion and Paladian, speaker honoraria from Teva and Zambon, and advisory board fees from Acadia. Author RH reports consulting fees from AbbVie, Academy for Continued Healthcare Learning, Acadia Pharmaceuticals, Acorda Therapeutics, Adamas Pharmaceuticals, Affriris, Alliance for Aging Research, Alphasights, Amneal Pharmaceuticals, ApoPharma, Aptis Partners LLC, Aranca, Axial Biotherapeutics, Axovant Sciences, Bain Capital, Baron Capital, Brittanna Pharmaceuticals, Cadent Therapeutics, Cerespir, Clearview Healthcare Partners, CNS Ratings LLC, Compass Group, DOB Health LLC, Decision Resources Group, Defined Health, Dellaus Consulting, Denali Therapeutics, Enterin, Evercore, Extera Partners, GE Healthcare, Gerson Lehrman Group, Global Kinetics Corporation, Guide Point Global, Health and Wellness Partners, Healthlogix, Heptares Therapeutics, Huron Consulting Group, lmpax Laboratories, Impel Neuropharma, lnhibikase, lntec Pharma Ltd., International Stem Cell Corporation, lntraMed Educational Group, IQVIA, Jazz Pharmaceutics, Kaiser, Kyowa Kirin Pharmaceutical Development, Kashiv Pharma LLC, L.E.K. Consulting, Lundbeck, Lundbeck A/S, MedaCorp, MEDIQ, Medscape, Medtronic, Michael J Fox Foundation, Mitsubishi Tanabe Pharmaceuticals, Movement Disorder Society, Neuro Challenge Foundation for Parkinson's, Neurocea LLC, Neurocrine Biosciences, Neuroderm, Northwestern University, Orbes, Orbes Medical Group, Orion, Parkinson's Foundation, Parkison Study Group, Partner's Healthcare, Penn Technology Partnership, Pennside Partners, Perception OpCo, Precision Effect, Phase Five Communications, Prescott Medical Group, Prilenia Therapeutics LLC, Projects in Knowledge, Regenera Pharma, SAi Med Partners LLC, Schlesinger Associates, Scion Neurostim LLC, Seagrove Partners, Seelos Therapeutics, Slingshot Insights, Sun Pharma, Sunovion Pharmaceuticals, Teva Pharmaceuticals, The Lockwood Group, USWorldMeds, WebMD, and Windrose Consulting Group; speaker fees from Acorda Therapeutics, Adamas Pharmaceuticals, Amneal Pharmaceuticals, Kyowa Kirin, Neurocrine Biosciences and US WorldMeds; research support from AbbVie, Acorda Therapeutics, AstraZeneca, Axovant Sciences, Biogen, Cavion, Centogene, Cerevance, Cerevel, Covance, Enterin, Global Kinetics Corp., Impax Laboratories LLC, Intec Pharma Ltd., Jazz Pharmaceuticals, Neuroderm, Lundbeck, Michael J Fox Foundation for Parkinson's Research, Neuraly, Pharma2B, F. Hoffman-La Roche, Revance Therapeutics, and Sunovion Pharmaceuticals; grant support from Parkinson's Foundation; and has stock option ownership in Axial Biotherapeutics and Inhibikase Therapeutics. Author SI reports honoraria for CME, and consultant fees, research grants, and/or promotional speaker fees on behalf of AbbVie, Acadia Pharmaceuticals, Acorda, Adamas Pharmaceuticals, Addex Therapeutics, Affiris, Alexva, Allergan, Amarantus Bioscience, Amneal, Aptinyx, Axial, Axovant, Benevolent, Biogen, Britannia Pharmaceuticals, Bukwang, Cadent, Cala, Cerecor, Cerevel, Cipla, Eli Lilly, Enterin, GE Healthcare, Global Kinetics, Impax Pharmaceuticals, Impel, Intec Pharma, Ipsen, IR Labs, Jazz, Kyowa, Lundbeck, Merz, Michael J. Fox Foundation, Mitsubishi Tanabe, Neuralys, Neurocrine Biosciences, Neuroderm, Parkinson's Study Group, Pharma2B, Prilenia, Promentis, Revance, Roche, Sanofi, Sunovion, Sun Pharma, Supernus, Teva, Theravance, and UCB. JL, RJ, and LL are former employees of Adamas Pharmaceuticals. AF is a former employee of Adamas Pharmaceuticals, and a current employee of Supernus Pharmaceuticals, Inc. Author CT reports research grants from Gateway LLC, Michael J Fox Foundation, Parkinson's Foundation, Parkinson's Study Group, and Roche/Genentech; grants and personal fees from Biogen Idee; and personal fees from 23andme, Acorda, Adamas Pharmaceuticals, Australia Parkinson's Mission, Cadent Therapeutics, CNS ratings, Gray Matter, Intec Pharma, Jazz Pharmaceuticals, Kyowa-Kirin Pharmaceuticals, Lundbeck Pharmaceuticals, Neurocrine Biosciences, Shake It Up Foundation, and Voyager Therapeutics. The authors declare that this study received funding from Adamas Pharmaceuticals, Inc and Supernus Pharmaceuticals, Inc. Adamas Pharmaceuticals, Inc had the following involvement in the study: Provided data and funding for MCIC calculations, medical writing support and participated in authorship of the paper. Supernus Pharmaceuticals had the following involvement in the study: Medical writing and editorial support.