title: Estimated Budget Impact of Increased Use of Mirabegron, A Novel Treatment for Overactive Bladder.
abstract: BACKGROUND
  Oral pharmacological treatment for overactive bladder (OAB) consists of antimuscarinics and the beta-3 adrenergic agonist mirabegron. Antimuscarinic adverse events (AEs) such as dry mouth, constipation, and blurry vision can result in frequent treatment discontinuation rates, leaving part of the OAB population untreated. Antimuscarinics also contribute to a patient's anticholinergic cognitive burden (ACB), so the Beers Criteria recommends cautious use of antimuscarinics in elderly patients who take multiple anticholinergic medications or have cognitive impairment. Since mirabegron does not affect the cholinergic pathways, it is unlikely to contribute to a patient's ACB.
  
  
  OBJECTIVE
  To estimate the health care costs associated with the pharmacological treatment of OAB with mirabegron and antimuscarinics from U.S. commercial payer and Medicare Advantage perspectives, using a budget impact model.
  
  
  METHODS
  For this budget impact model, 2 analyses were performed. The primary analysis estimated the budgetary impact of increasing the use of mirabegron in a closed patient cohort treated with oral pharmacological treatments. The secondary analysis modeled the economic impact in an open cohort by allowing untreated patients to begin treatment with mirabegron after potential contraindication, intolerance, or lack of effectiveness of antimuscarinics. The analyses were performed over a 3-year time horizon. The economic impact of increased mirabegron use was quantified using direct medical costs, including prescription costs and health resource utilization (HRU) costs. Costs of comorbidities included pharmacy and medical costs of treating OAB-related urinary tract infections (UTI), skin rashes, and depression. An analysis of a large single-site integrated health network database was commissioned to quantify ACB-related HRU in terms of the increases in yearly outpatient and emergency department visits. Based on this analysis, the model associated each unit increase in ACB score with increased HRU and probability of mild cognitive impairment. Clinical outcomes of increased use of mirabegron were presented as the number of AEs and comorbidity episodes that could be avoided. One-way sensitivity analyses were performed to quantify the expected budget impact over the range of uncertainty for the key input variables.
  
  
  RESULTS
  Primary analysis calculated the impact of increasing the use of mirabegron from 4.5% to 5.3%, 7.1%, and 9.4% in years 1, 2, and 3, respectively, among oral pharmacological OAB treatments that included generic and branded antimuscarinics: oxybutynin, tolterodine, trospium, darifenacin, fesoterodine, and solifenacin. For a 1 million-member U.S. commercial payer plan, the total prescription costs increased, and the total medical costs decreased during the 3-year time horizon, yielding increases of $0.005, $0.016, and $0.031 from current per member per month (PMPM) costs and $0.90, $2.92, and $5.53 from current per treated member per month (PTMPM) costs, an average of less than 2% of current OAB treatment costs. For the Medicare Advantage plan, the resulting incremental PMPM costs were $0.010, $0.034, and $0.065, and the incremental PTMPM costs were $0.93, $3.04, and $5.76; all were less than 4% of the current cost. The secondary analysis estimated the budgetary effects of reducing the untreated population by 1% annually by initiating treatment with mirabegron. For a commercial payer, this resulted in PMPM cost increases of $0.156, $0.311, and $0.467 from the current value, while the incremental PTMPM cost increased by $6.17, $11.67, and $16.61. For the Medicare Advantage plan, the incremental increases in PMPM costs were $0.277, $0.553, and $0.830, and in PTMPM costs were $6.42, $12.15, and $17.29. Clinically, treating more OAB patients resulted in fewer OAB-related comorbidities from both health plan perspectives, since most events associated with nontreatment could be avoided. In the Medicare Advantage population of the secondary analysis, the total numbers of avoided events were predicted as 452 UTIs, 2,598 depression diagnoses, and 3,020 skin rashes during the time horizon of the model.
  
  
  CONCLUSIONS
  Mirabegron addresses an unmet need for therapy for certain OAB patients, for whom antimuscarinics are not recommended because of a risk of cognitive impairment and who are intolerant to the anticholinergic AEs. Using mirabegron involves moderate additional economic cost to a commercial or Medicare Advantage health plan for which medical cost savings can offset a substantial part of increased pharmacy costs.
  
  
  BACKGROUND
  Funding for this study was provided by Astellas. Perk, Wielage, T. Klein, and R. Klein are employed by Medical Decision Modeling, a contract research company that was paid to perform the described outcomes research and build the model contained in this study. Campbell and Perkins are employed by the Regenstrief Institute, which conducted a database analysis for this research. Campbell reports consultancy fees from Astellas, as well as pending grants from Merck, Sharpe, and Dohme Corp. Posta, Yuran, and Ng are employed by Astellas Pharma Global Development, the developer of mirabegron. Study concept and design were contributed by Perk, Wielage, R. Klein, and Ng. Campbell, T. Klein, and Perkins took the lead in data collection, assisted by Perk, Wielage, and Ng. Data interpretation was performed by Posta and Yuran, along with Perk, Wielage, R. Klein, Ng, Campbell, and Perkins. The manuscript was written by Perk and R. Klein, along with Wielage, T. Klein, Posta, Yuran, and Ng, and revised by all the authors.
authors: 1 Medical Decision Modeling, Indianapolis, Indiana.
authors: Sinem
authors: S
authors: Perk
authors: 1 Medical Decision Modeling, Indianapolis, Indiana.
authors: Ronald C
authors: RC
authors: Wielage
authors: 2 Center for Aging Research, Regenstrief Institute, Indianapolis, Indiana, and Purdue University College of Pharmacy, West Lafayette, Indiana.
authors: Noll L
authors: NL
authors: Campbell
authors: 1 Medical Decision Modeling, Indianapolis, Indiana.
authors: Timothy M
authors: TM
authors: Klein
authors: 3 Center for Aging Research, Regenstrief Institute, Indianapolis, Indiana.
authors: Anthony
authors: A
authors: Perkins
authors: 4 Medical Affairs, Americas, Astellas Pharmaceutical Global Development, Northbrook, Illinois.
authors: Linda M
authors: LM
authors: Posta
authors: 4 Medical Affairs, Americas, Astellas Pharmaceutical Global Development, Northbrook, Illinois.
authors: Thomas
authors: T
authors: Yuran
authors: 1 Medical Decision Modeling, Indianapolis, Indiana.
authors: Robert W
authors: RW
authors: Klein
authors: 4 Medical Affairs, Americas, Astellas Pharmaceutical Global Development, Northbrook, Illinois.
authors: Daniel B
authors: DB
authors: Ng
mesh_terms: D000083:Acetanilides / Q000191:economics* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002017:Budgets / Q000639:trends; D017048:Health Care Costs / Q000639:trends; D006801:Humans; D007348:Insurance, Health / Q000191:economics / Q000639:trends; D020398:Medicare Part C / Q000191:economics / Q000639:trends; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000191:economics / Q000627:therapeutic use; D013844:Thiazoles / Q000191:economics* / Q000627:therapeutic use; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy / Q000191:economics* / Q000453:epidemiology; D064804:Urological Agents / Q000191:economics* / Q000627:therapeutic use
chemical_list: D000083:Acetanilides; D018727:Muscarinic Antagonists; D013844:Thiazoles; D064804:Urological Agents; C520025:mirabegron