PMID- 37713748 OWN - NLM STAT- MEDLINE DCOM- 20231009 LR - 20240211 IS - 1873-5126 (Electronic) IS - 1353-8020 (Print) IS - 1353-8020 (Linking) VI - 115 DP - 2023 Oct TI - Comparative safety of antimuscarinics versus mirabegron for overactive bladder in Parkinson disease. PG - 105822 LID - S1353-8020(23)00901-X [pii] LID - 10.1016/j.parkreldis.2023.105822 [doi] AB - BACKGROUND: Overactive bladder (OAB) is a common non-motor symptom of Parkinson disease (PD), often treated with antimuscarinics or beta-3 agonists. There is lack of evidence to guide OAB management in PD. OBJECTIVES: To assess the comparative safety of antimuscarinics versus beta-3 agonists for OAB treatment in PD. METHODS: We employed a new-user, active-comparator cohort study design. We included Medicare beneficiaries age >/=65 years with PD who were new users of either antimuscarinic or beta-3 agonist. The primary outcome was any acute care encounter (i.e., non-elective hospitalization or emergency department visit) within 90 days of OAB drug initiation. The main secondary outcome was a composite measure of acute care encounters for anticholinergic related adverse events (AEs). Matching on high-dimensional propensity score (hdPS) was used to address potential confounding. We used Cox proportional hazards models to examine the association between OAB drug category and outcomes. We repeated analyses for 30- and 180-day follow-up periods. RESULTS: We identified 27,091 individuals meeting inclusion criteria (mean age: 77.8 years). After hdPS matching, antimuscarinic users had increased risks for any acute care encounter (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.12-1.37) and encounters for anticholinergic related AEs (HR 1.18, 95% CI 1.04-1.34) compared to beta-3 agonist users. Similar associations were observed for sensitivity analyses. CONCLUSIONS: Among persons with PD, anticholinergic initiation was associated with a higher risk of acute care encounters compared with beta-3 agonist initiation. The long-term safety of anticholinergic vs. beta-3 agonist therapy in the PD population should be evaluated in a prospective study. CI - Copyright (c) 2023 Elsevier Ltd. All rights reserved. FAU - Abraham, Danielle S AU - Abraham DS AD - Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Neurology Translational Center for Excellence for Neuroepidemiology and Neurological Outcomes Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Center for Real-world Effectiveness and Safety of Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. FAU - Pham Nguyen, Thanh Phuong AU - Pham Nguyen TP AD - Department of Neurology Translational Center for Excellence for Neuroepidemiology and Neurological Outcomes Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Center for Real-world Effectiveness and Safety of Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Biostatistics, University of Pennsylvania Perelman School of Medicine, Epidemiology and Informatics, Philadelphia, PA, USA. FAU - Newcomb, Craig W AU - Newcomb CW AD - Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Biostatistics, University of Pennsylvania Perelman School of Medicine, Epidemiology and Informatics, Philadelphia, PA, USA. FAU - Gray, Shelly L AU - Gray SL AD - Department of Pharmacy, University of Washington School of Pharmacy, Seattle, WA, USA. FAU - Hennessy, Sean AU - Hennessy S AD - Center for Real-world Effectiveness and Safety of Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Biostatistics, University of Pennsylvania Perelman School of Medicine, Epidemiology and Informatics, Philadelphia, PA, USA. FAU - Leonard, Charles E AU - Leonard CE AD - Center for Real-world Effectiveness and Safety of Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Biostatistics, University of Pennsylvania Perelman School of Medicine, Epidemiology and Informatics, Philadelphia, PA, USA. FAU - Liu, Qing AU - Liu Q AD - Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Biostatistics, University of Pennsylvania Perelman School of Medicine, Epidemiology and Informatics, Philadelphia, PA, USA. FAU - Weintraub, Daniel AU - Weintraub D AD - Parkinson's Disease Research, Education and Clinical Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA; Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. FAU - Willis, Allison W AU - Willis AW AD - Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Neurology Translational Center for Excellence for Neuroepidemiology and Neurological Outcomes Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Center for Real-world Effectiveness and Safety of Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Biostatistics, University of Pennsylvania Perelman School of Medicine, Epidemiology and Informatics, Philadelphia, PA, USA. Electronic address: allison.willis2@pennmedicine.upenn.edu. LA - eng GR - K24 AG075234/AG/NIA NIH HHS/United States GR - P30 AG059302/AG/NIA NIH HHS/United States GR - R01 NS099129/NS/NINDS NIH HHS/United States GR - R24 AG064025/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20230904 PL - England TA - Parkinsonism Relat Disord JT - Parkinsonism & related disorders JID - 9513583 RN - 0 (Muscarinic Antagonists) RN - MVR3JL3B2V (mirabegron) RN - 0 (Acetanilides) RN - 0 (Cholinergic Antagonists) RN - 0 (Urological Agents) SB - IM MH - Humans MH - Aged MH - United States MH - Muscarinic Antagonists/adverse effects MH - *Urinary Bladder, Overactive/diagnosis MH - Cohort Studies MH - Prospective Studies MH - *Parkinson Disease/complications/drug therapy MH - Medicare MH - Acetanilides/therapeutic use MH - Cholinergic Antagonists/adverse effects MH - Treatment Outcome MH - *Urological Agents/therapeutic use PMC - PMC10853986 MID - NIHMS1931898 OTO - NOTNLM OT - Anticholinergics OT - Antimuscarinics OT - Mirabegron OT - Overactive bladder OT - Parkinson disease COIS- Declaration of competing interest Dr. Abraham received financial compensation from the Parkinson's Foundation. Dr. Pham Nguyen is a member of the 2022-2023 Junior Investigator Intensive Program of the U.S. Deprescribing Research Network, which is funded by the National Institute on Aging [Grant #R24AG064025] and receives support from the National Institutes of Health [Grants #R01NS099129, #R01AG02515215, #R01AG06458903] and Acadia Pharmaceuticals Inc. Dr. Hennessy directs the University of Pennsylvania's Center for Real-world Effectiveness and Safety of Therapeutics (CREST), which receives funds from Pfizer and Sanofi to support pharmacoepidemiology education and has received grants from Pfizer, and Johnson and Johnson during the conduct of the study, consulted for Novo Nordisk, Arbor Pharmaceuticals, the Medullary Thyroid Cancer Consortium (Novo Nordisk, AstraZeneca, GlaxoSmithKline and Eli Lilly), Biogen, Intercept Pharmaceuticals, Provention Bio, bluebird bio, and Amylyx Pharmaceuticals, and is a special government employee of the U.S. Food and Drug Administration. Dr. Leonard is an Executive Committee Member of the University of Pennsylvania's CREST and recently received honoraria from the American College of Clinical Pharmacy Foundation, the Consortium for Medical Marijuana Clinical Outcomes Research, the University of Florida, the University of Massachusetts, and the Scientific and Data Coordinating Center for the NIDDK-funded Chronic Renal Insufficiency Cohort Study; he is a Special Government Employee of the United States (US) Food and Drug Administration and consults for their Reagan-Udall Foundation and receives travel support from John Wiley & Sons. Dr. Leonard consults for TriNetX and Novo Nordisk. Dr. Leonard's spouse is an employee of Merck; neither Dr. Leonard nor his spouse owns stock in the company. Dr. Weintraub receives support from the National Institutes of Health [Grant #R01NS099129] and has also received research funding or support from Michael J. Fox Foundation for Parkinson's Research, Alzheimer's Therapeutic Research Initiative (ATRI), Alzheimer's Disease Cooperative Study (ADCS), the International Parkinson and Movement Disorder Society (IPMDS); honoraria for consultancy from Acadia Pharmaceuticals Inc., Aptinyx, Biogen, Bracket, CHDI Foundation, Clintrex LLC, Enterin, F. Hoffmann-La Roche Ltd, Ferring, Promentis, Sunovion, and Takeda; and license fee payments from the University of Pennsylvania for the QUIP and QUIP-RS. Dr. Willis receives financial support from National Institutes of Health [Grants #R01NS099129, #K24AG075234, #P30AG059302], the Parkinson's Foundation, Acadia Pharmaceuticals Inc., and the University of Pennsylvania. All other authors declared no competing interests for this work. EDAT- 2023/09/16 05:42 MHDA- 2023/10/09 06:42 PMCR- 2024/10/01 CRDT- 2023/09/15 18:01 PHST- 2023/05/10 00:00 [received] PHST- 2023/07/25 00:00 [revised] PHST- 2023/08/23 00:00 [accepted] PHST- 2024/10/01 00:00 [pmc-release] PHST- 2023/10/09 06:42 [medline] PHST- 2023/09/16 05:42 [pubmed] PHST- 2023/09/15 18:01 [entrez] AID - S1353-8020(23)00901-X [pii] AID - 10.1016/j.parkreldis.2023.105822 [doi] PST - ppublish SO - Parkinsonism Relat Disord. 2023 Oct;115:105822. doi: 10.1016/j.parkreldis.2023.105822. Epub 2023 Sep 4.