Real-World Phosphate Binder Use among Dialysis-Dependent Patients with CKD.

INTRODUCTION: For patients with chronic kidney disease (CKD), the need for phosphate binder (PB) treatment peaks at onset of dialysis. This real-world study assessed rates of PB utilization and switching in patients with dialysis-dependent CKD (DD-CKD). METHODS: We identified patients with PB utilization among those with prevalent DD-CKD using 2018-2019 Medicare Parts A/B/D data. Patients were assigned to cohorts based on primary (most frequently used) PB among calcium acetate, ferric citrate, lanthanum carbonate, sevelamer (hydrochloride and carbonate), sucroferric oxyhydroxide. We measured proportion of patients who were adherent (proportion of days covered >80%) and persistent (patients whose last 90 days of outpatient dialysis reported PB use). Net switching rates were calculated as the difference between switches to and from the primary agent. RESULTS: We identified 136,912 patients with PB use. Proportion of patients adherent ranged from 63.8% (lanthanum carbonate) to 67.7% (sevelamer) and persistent from 85.1% (calcium acetate) to 89.5% (ferric citrate). Most patients (73%) used the same PB throughout the study. Overall, 20.5% of patients experienced one switch and 2.3% two or more. Positive net switching rates were observed for ferric citrate, sucroferric oxyhydroxide, and lanthanum carbonate (2-10%) but negative for sevelamer and calcium acetate (-2% to -7%). CONCLUSION: Adherence and persistence rates were low with slight variation across PBs. Net positive switching occurred for ferric citrate, sucroferric oxyhydroxide, and lanthanum carbonate. Further studies are needed to determine the reasons for these findings and could identify opportunities for better control of phosphate levels among patients with CKD.

Patient experience with subcutaneous immunoglobulin 20%, Ig20Gly, for primary immunodeficiency diseases: a prespecified post hoc analysis of combined data from 2 pivotal trials.

BACKGROUND: Often, patients with primary immunodeficiency diseases (PID), which are marked by the absence or loss of functional antibodies, require lifelong treatment with immunoglobulin (IG) replacement therapy administered either intravenously (intravenous immunoglobulin [IVIG]) or subcutaneously (subcutaneous immunoglobulin [SCIG]). In patients with PID, the 20% SCIG product, Ig20Gly, was shown to be efficacious and well tolerated in 2 phase 2/3 trials conducted in North America and Europe. This analysis evaluated patient satisfaction with Ig20Gly therapy and treatment preferences. METHODS: This prespecified post hoc analysis showed combined data from 2 Ig20Gly pivotal trials. Treatment satisfaction was assessed in the pre-Ig20Gly period and after ≥11 months of Ig20Gly treatment using the Life Quality Index (LQI; both studies) and the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9; North American study only). Treatment preference was assessed using a survey at the end of the European study. Median within-patient differences in LQI and TSQM-9 scores between the pre-Ig20Gly period and the end of the Ig20Gly treatment period were assessed using the Wilcoxon signed-rank test. RESULTS: A total of 113 patients (n = 68 [North American]; n = 45 [Europe]) with PID were included in the analysis. In the combined LQI analysis (n = 110), significant improvements were observed in the treatment interference (median ∆: + 2.8; P = 0.006) and therapy setting (median ∆: + 5.6; P < 0.0001) domains, and in the item-level scores for convenience (median ∆: + 1.0; P < 0.0001) and interference with work/school (median ∆: + 1.0; P = 0.0001) categories. In the subgroup analyses, significant improvements in the treatment interference and therapy setting domains and the convenience and interference with work/school items were observed for those who had previously received treatment outside the home, those who had previously received IVIG, and those in the North American study. Significant improvements were observed in the TSQM-9 treatment convenience domain (median ∆: + 11.1; P < 0.0001) and selected item-level scores in the North American study. In the European study, most (88.9%) patients preferred to continue Ig20Gly versus other IG treatments. CONCLUSIONS: After ≥11 months of taking Ig20Gly, patients reported high levels of treatment satisfaction, convenience, and preference for Ig20Gly, with consistent results across studies and use of multiple patient-reported outcome measures.

Aromatic amino acid decarboxylase deficiency: Molecular and metabolic basis and therapeutic outlook.

Aromatic-l-amino acid decarboxylase (AADC) deficiency is an ultra-rare inherited autosomal recessive disorder characterized by sharply reduced synthesis of dopamine as well as other neurotransmitters. Symptoms, including hypotonia and movement disorders (especially oculogyric crisis and dystonia) as well as autonomic dysfunction and behavioral disorders, vary extensively and typically emerge in the first months of life. However, diagnosis is difficult, requiring analysis of metabolites in cerebrospinal fluid, assessment of plasma AADC activity, and/or DNA sequence analysis, and is frequently delayed for years. New metabolomics techniques promise early diagnosis of AADC deficiency by detection of 3-O-methyl-dopa in serum or dried blood spots. A total of 82 dopa decarboxylase (DDC) variants in the DDC gene leading to AADC deficiency have been identified and catalogued for all known patients (n = 123). Biochemical and bioinformatics studies provided insight into the impact of many variants. c.714+4A>T, p.S250F, p.R347Q, and p.G102S are the most frequent variants (cumulative allele frequency = 57%), and c.[714+4A>T];[714+4A>T], p.[S250F];[S250F], and p.[G102S];[G102S] are the most frequent genotypes (cumulative genotype frequency = 40%). Known or predicted molecular effect was defined for 79 variants. Most patients experience an unrelenting disease course with poor or no response to conventional medical treatments, including dopamine agonists, monoamine oxidase inhibitors, and pyridoxine derivatives. The advent of gene therapy represents a potentially promising new avenue for treatment of patients with AADC deficiency. Clinical studies based on the direct infusion of engineered adeno-associated virus type 2 vectors into the putamen have demonstrated acceptable safety and tolerability and encouraging improvement in motor milestones and cognitive symptoms. The success of gene therapy in AADC deficiency treatment will depend on timely diagnosis to facilitate treatment administration before the onset of neurologic damage.

Evaluating Outcomes in Patients with Overactive Bladder within an Integrated Healthcare Delivery System Using a Treatment Patterns Analyzer.

BACKGROUND: Overactive bladder (OAB) is a relatively common disease that has been linked to a variety of comorbidities, reductions in quality of life, and increased healthcare costs. Antimuscarinic agents are the standard of care among pharmacologic treatments for OAB, but these drugs are linked to high levels of anticholinergic burden, especially in the elderly. OBJECTIVE: To demonstrate how efficient data analysis can be used to identify gaps in care as a result of improvement strategies for OAB within an integrated healthcare delivery system setting. METHODS: We developed an OAB treatment patterns analyzer, a clinical outcomes software analysis program, to identify gaps in care, high anticholinergic burden, and potential quality improvement initiatives. Deidentified pharmacy and medical claims data from an integrated delivery network were imported into the OAB treatment patterns analyzer. Patients with a diagnosis of OAB who were continuously enrolled in the network between January 1, 2009, and December 31, 2013, were identified and were imported into the analyzer. The analyzer used National Drug Code; International Classification of Diseases, Ninth Edition, Clinical Modification; Current Procedural Terminology; and UB-92 codes to measure treatment patterns, comorbid conditions, anticholinergic burden, concomitant use with anticholinesterases, costs, and healthcare resource utilization. RESULTS: Of 157,710 members in the integrated delivery network population, 7309 patients met the study eligibility criteria. Of patients taking medications for OAB, 85% were nonadherent and 73% discontinued treatment within 1 year. Among 1147 patients in the integrated healthcare delivery system who were using medications for OAB, 39 (3.4%) patients were concomitantly taking anticholinesterase drugs and an antimuscarinic agent. The per-month plan-paid cost per member was $318.67. Of all the patients with OAB within the population, the rates of all-cause office visits, emergency department visits, and hospitalizations were 81%, 6%, and 4%, respectively. The rate of clinically relevant anticholinergic burden was 16%, with higher rates among patients with dementia who were also receiving a branded (20%) or generic (24%) antimuscarinic drug. CONCLUSION: In patients using medications for the treatment of OAB, the rates of medication persistence and adherence were poor. Antimuscarinic medications may place certain patient populations at risk for increased anticholinergic burden. Data included in the analyzer can be used to implement member-specific strategies to prevent poor outcomes and reduce associated healthcare costs and utilization.

Effect of Potentially Inappropriate Use of Antimuscarinic Medications on Healthcare Use and Cost in Individuals with Overactive Bladder.

OBJECTIVES: To examine potentially inappropriate medication (PIM) use in older adults initiating an antimuscarinic medication for the treatment of overactive bladder (OAB). DESIGN: Retrospective database analysis. SETTING: Medical and pharmacy claims data. PARTICIPANTS: Medicare Advantage Prescription Drug Plan members aged 65 and older newly initiated on an antimuscarinic OAB treatment were identified and assigned to PIM and non-PIM comparison groups based on 2012 American Geriatrics Society Beers Criteria and/or the presence of an anticholinergic medication interaction at the time of initiation of treatment (N = 66,275). MEASUREMENTS: Healthcare costs and OAB medication use. RESULTS: Of members initiated on an antimuscarinic OAB medication, 31.1% had a drug-drug or drug-disease or syndrome interaction. Dementia was the most common disease or syndrome interaction (11.3%), followed by constipation (8.6%) and delirium (2.9%). Paroxetine (2.6%), amitriptyline (2.2%), cyclobenzaprine (1.7%), and meclizine (1.6%) were the most common interacting medications. Subjects in the PIM group had greater healthcare costs over 12 months of follow-up ($12,001) than those in the non-PIM group ($9,373) after controlling for baseline characteristics (P < .001). There was no difference between the PIM and the non-PIM groups in odds of discontinuing OAB treatment at 12 months after controlling for baseline characteristics (odds ratio = 0.98, 95% confidence interval = 0.89-1.07, P = .63). CONCLUSION: Potentially inappropriate medication use was highly prevalent and was associated with greater total healthcare costs. Providers should carefully consider medical history and concurrent medication use when initiating antimuscarinic medication for the treatment of OAB. Development of interventions to reduce potentially inappropriate use of antimuscarinics in individuals with OAB is warranted.

Oral pharmacotherapy for overactive bladder in older patients: mirabegron as a potential alternative to antimuscarinics.

OBJECTIVE: Overactive bladder (OAB) is a particular challenge to treat in older adults with co-morbid conditions taking multiple medications. Antimuscarinics (e.g., solifenacin, fesoterodine) and ß3-adrenergic receptor agonists (mirabegron) are similarly efficacious; however, antimuscarinics may be associated with side effects that result in poor persistence and contribute to anticholinergic burden, particularly in those taking other medications with anticholinergic properties. With a mechanism of action distinct from antimuscarinics, mirabegron has a different tolerability profile and does not contribute to anticholinergic burden. The objective of this review was to compare and contrast the tolerability profiles of antimuscarinics and mirabegron in older patients to inform practice. METHODS: Prospective trials or retrospective subgroup analyses of antimuscarinics for the treatment of OAB in older patients were identified through a search of PubMed. Tolerability data and results of subgroup analyses of mirabegron in patients aged ≥65 and ≥75 years from a pooled analysis of three trials each of 12 weeks and a 1 year trial are described. RESULTS: Anticholinergic adverse events (AEs) including dry mouth and constipation were more frequent with antimuscarinics versus mirabegron. In patients aged ≥65 years, dry mouth occurred with a six-fold higher incidence with tolterodine extended-release (ER) 4 mg than with mirabegron 25 mg or 50 mg over 12 weeks, and a three-fold higher incidence with tolterodine ER than mirabegron 50 mg over 1 year. Mirabegron had a low incidence of central nervous system effects. A systematic review of the cardiovascular safety profile of mirabegron has not identified any clinically significant effects on blood pressure or pulse rate at therapeutic doses amongst patients aged ≥65 years. CONCLUSIONS: Mirabegron has a more favorable tolerability profile than antimuscarinics amongst older patients and may provide an improved benefit-to-risk ratio and therefore be considered as an alternative to antimuscarinics for older patients.

Persistence and adherence with the new beta-3 receptor agonist, mirabegron, versus antimuscarinics in overactive bladder: Early experience in Canada.

INTRODUCTION: Antimuscarinics are the principal pharmacological treatment for overactive bladder (OAB), but frequently give rise to anticholinergic side effects, such as dry mouth, a factor leading to poor persistence. The ß3-adrenoceptor agonist mirabegron is devoid of significant anticholinergic activity, while being effective in OAB. We evaluated persistence and adherence with mirabegron versus antimuscarinics over 12 months. METHODS: We obtained retrospective claims from a Canadian Private Drug Plan database for patients 18 years old and over, with a first claim for mirabegron or antimuscarinics during a 6-month index period (April-September 2013). A 6-month look-back identified those with no prior claims for OAB medication (treatment-naïve) or ≥1 prior OAB drug (treatment-experienced). Time to end of persistence (≥30 day therapy gap or switch of therapy) was evaluated over 12 months; adherence with medication (medication possession ratio) was also measured. RESULTS: Persistence data from 19 485 patients (74% female, 92% naïve, 19.9% aged ≥65 years) showed that for experienced patients the median number of days on mirabegron was 299 days, compared with a range of 96 to 242 days for the different antimuscarinics; for naïve patients, it was 196 versus 70 to 100 days, respectively. Persistence at 12 months was for mirabegron 39% versus 14% to 35% for antimuscarinics, (experienced) and 30% mirabegron versus 14% to 21% antimuscarinics, (naïve). Patients taking mirabegron demonstrated statistically significantly greater adherence than those taking antimuscarinics. CONCLUSION: Patients who received mirabegron remained longer on treatment than those treated with antimuscarinics, and had higher 12-month persistence and adherence rates.

Challenges in the Pharmacological Management of Nursing Home Residents with Overactive Bladder or Urinary Incontinence.

OBJECTIVES: To determine the proportion of nursing home (NH) residents (NHR) with overactive bladder (OAB) or urinary incontinence (UI) with potential pharmacodynamic contraindications to antimuscarinic treatment because of concomitant anticholinergic medications or acetylcholinesterase inhibitors (AChEIs) and nonpharmacological limitations to antimuscarinic treatment. DESIGN: Cross-sectional retrospective analysis. SETTING: U.S. skilled nursing facilities. PARTICIPANTS: Nursing home residents with a diagnosis of OAB or UI. MEASUREMENTS: Linked and deidentified pharmacy claims and Minimum Data Set (MDS) 3.0 records (October 1, 2010 to September 30, 2012). RESULTS: Of NHRs, 71.3% received at least one anticholinergic medication. Medications that can cause or worsen UI were used commonly. AChEIs and antimuscarinic treatment were prescribed concurrently in 24% of NHRs with OAB or UI. NHRs with OAB or UI were more likely to have concurrent moderate to severe cognitive impairment (MSCI) (70.1%) than those without (29.9%) (P < .001). NHRs with or without OAB or UI and with MSCI were more likely to be treated with an anticholinergic medication than those without MSCI (P = .001). When NHRs with MSCI, severe mobility impairment (SMI), and anticholinergic medication and AChEI use were excluded, only a small proportion of NHRs were potential candidates for antimuscarinic treatment (6.6% with OAB or UI, 6.2% with UI). CONCLUSIONS: This study advances understanding of the challenges in prescribing antimuscarinic treatment safely and appropriately in elderly NHRs with a high prevalence of drug interactions, underlying MSCI, and SMI.

Clinical Burden and Nonpharmacologic Management of Nursing Facility Residents with Overactive Bladder and/or Urinary Incontinence.

OBJECTIVE: To identify clinical characteristics of residents with a diagnosis of overactive bladder (OAB) and/or urinary incontinence (UI) to determine the prevalence of comorbidities, severe mobility impairment (SMI), moderate-to-severe cognitive impairment (MSCI), and a toileting program and the response to that program. DESIGN: Cross-sectional retrospective analysis. SETTING: Skilled nursing facilities. PATIENTS, PARTICIPANTS: Residents with a diagnosis of OAB and/or UI and an age range, and gender frequency-matched 1:1 control cohort without OAB and/or UI. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): De-identified Minimum Data Set data 3.0 records (October 1, 2010, to September 30, 2012). RESULTS: Of the 175,632 residents, 65% had a diagnosis of UI and 1% had a diagnosis of OAB. Those with UI and/or OAB were more likely to have MSCI (mean Brief Inventory of Mental Status score 10.2 ± 4.5 vs. 12.5 ± 3.6; P = 0.001) and SMI (49.4% vs. 26.4%; P < 0.001), multiple comorbid conditions, falls and falls with injury, hip fractures (5.5% vs. 4.9%; P < 0.001), urinary tract infections (21.4% vs. 16.5%; P = 0.001), and moisture-associated skin damage (5.2% vs. 2.6%; P = 0.001) than the control cohort. Toileting programs were attempted more often (17.0% vs. 5.1%; P < 0.001) in those with UI and/or OAB but were only minimally successful, with 4.2% having decreased wetness and 0.9% being completely dry. CONCLUSION: Residents with UI and/or OAB exhibit a higher burden of MSCI, SMI, and comorbidities than do residents without these diagnoses. Nonpharmacologic therapies such as toileting programs should be a primary focus in the nursing facility.

Opioid Medication Practices Observed in Chronic Pain Patients Presenting for All-Causes to Emergency Departments: Prevalence and Impact on Health Care Outcomes.

BACKGROUND: Chronic pain is a significant health problem that affects an estimated 100 million American adults (aged ≥ 18 years). Chronic pain affects more individuals than heart disease, stroke, diabetes, and cancer combined. Chronic pain sufferers cost up to $635 billion annually in medical treatment and lost productivity. Opioids are commonly used to treat chronic pain, but their metabolic interactions with concurrently prescribed medications for concomitant disease burdens can affect potency and efficacy of pain therapy. Additionally, misuse of short-acting opioids (SAOs) for chronic pain versus breakthrough pain can create gaps in pain relief. These potentially suboptimal prescribing practices may contribute to the high economic impact associated with chronic pain.  OBJECTIVE: To examine the prevalence of suboptimal opioid therapy and the associated health care costs resulting from these prescribing practices in real-world patients presenting for all-causes to the emergency department (ED).  METHODS: This retrospective observational database cohort analysis used the linked Premier-Optum database and included patients with ED visits from 2006 to 2010 having ≥ 60 days supply of opioids in the 75 days prior to the visit. Suboptimal prescribing practices were identified as patients with (a) drug-drug exposures (DDEs), defined as cytochrome P-450 (CYP-450)-metabolized opioids prescribed concurrently with CYP-450 inhibitors or inducers and/or (b) monotherapy with SAOs. Comorbid conditions and principal diagnoses were documented. Readmission rates to the ED and hospital within 72 hours as well as ≤ 30, ≤ 45, ≤ 60, and ≤ 90 days were computed. Total costs for health care were calculated, and reimbursement rates were normalized using 2011 Medicare severity diagnosis-related group (MS-DRG) and CPT-4 information. Nonparametric bootstrapping to adjust for patient comorbidities was applied to cost data. RESULTS: Of the 9,214 patients identified with chronic pain, potentially suboptimal medication practices prior to the index ED visit were found for 8,539 (92.6%) patients. These appeared to be corrected in 345 (4.0%) patients before leaving the ED. Of 675 (7.3%) patients without prior DDE or exclusive use of SAOs, 345 (51.1%) patients were discharged with one of these. Of the 8,352 patients who left the ED with DDE or exclusive use of SAOs, 1,525 (18.3%) left with a DDE without exclusive SAO use; 4,812 (57.6%) left with both DDE and exclusive SAO use; and 2,015 (24.1%) left with only exclusive SAO use. Only 862 (9.3%) patients from the entire cohort left the ED without DDE or exclusive SAO use. Patients identified with suboptimal opioid use were aged 50 ± 13.5 years and were predominantly female (64.0%). Hypertension (44.0%), fluid and electrolyte disorders (32.7%), chronic pulmonary disease (22.8%), depression (19.6%), diabetes without chronic complications (16.2%), and drug abuse (15.6%) were the most prevalent comorbid conditions identified. The most prevalent principal diagnoses involved symptoms and signs of ill-defined conditions (36.5%), injury and poisoning (18.2%), and diseases of the musculoskeletal system (13.2%). The majority of revisits to the ED and hospital admissions occurred within 72 hours (73.6%) of the index visit and within 30 days (70%), respectively. When adjusted total costs were compared for all patients whose opioid use included DDE versus those without, a significantly greater cost (P less than 0.05) was observed at every time period except ≤ 72 hours. Respective mean increases in costs were $581, $689, $773, and $1,275 at 30, 45, 60, and 90 days. Exclusive SAO use with or without DDE resulted in a significant increase (P less than 0.05) in mean costs at all times: $214 at 72 hours; $836 at 30 days; $1,023 at 45 days; $1,022 at 60 days; and $1,536 at 90 days.  CONCLUSIONS: This study identified potentially suboptimal opioid prescribing practices in a real-world population presenting for all-causes to the ED. The observed rate of ED revisits and inpatient admissions in these patients was associated with increased health care costs. These findings suggest that the ED has the future potential to serve as an ideal setting to identify and correct such practices, thereby improving patient care and reducing resource use and beneficiary costs.

Alpha blocker monotherapy versus combination therapy with antimuscarinics in men with persistent LUTS refractory to alpha-adrenergic treatment: patterns of persistence.

INTRODUCTION: Patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) often present with voiding and storage symptoms, which may require combination therapy with an alpha blocker and an antimuscarinic (AM). This study compared treatment persistence in LUTS/BPH patients on alpha blocker monotherapy with those using combination alpha blocker and AM therapy (AB/AM). MATERIALS AND METHODS: Retrospective analysis of anonymized patient longitudinal prescription reimbursement claims data. All patients who had claims for any of four alpha blocker medications and six AM agents during an index period from April 1, 2011 to March 31, 2012 were included. For the combination therapy group, the effect of adherence with the AM medication on persistence to the alpha blocker was examined. RESULTS: Patients on AB/AM combination therapy remained on alpha blockers for longer than those on alpha blocker monotherapy (p = 0.04); 92.4% were persistent at 3 months versus 89.0%, and at 1 year 50.8% were persistent versus 49.6%, respectively. The highest number of days on therapy was reported for tamsulosin plus solifenacin. As confirmed by multivariate analysis, patients with the highest adherence to AM medication (= 80%) persisted on alpha blockers for longer than those with the lowest (< 50%) adherence (p < 0.05). CONCLUSIONS: Patients taking an AM in combination with an alpha blocker showed greater persistence with alpha blocker treatment over a 1 year period. When an AM is combined with an alpha blocker in patients with LUTS/BPH, the additional medication burden does not have a negative impact on persistence and may even improve it.

Treatment Patterns for Patients on Overactive Bladder Therapy: A Retrospective Statistical Analysis Using Canadian Claims Data.

Background: Overactive bladder (OAB) is a chronic condition which may be associated with a significant negative impact on quality of life. Antimuscarinic drugs are currently the mainstay of medical therapy, but persistence and adherence are generally poor. Treatment switching may be considered in order to maximise benefits from pharmacological therapy, but there are relatively few data on OAB therapy switching to second and third-lines of medication. There are also few formal analyses on the impact of age, gender and choice of initial OAB drug on discontinuation rates. Objectives: To investigate discontinuation rates with antimuscarinics in patients newly starting OAB therapy, with regard to patterns of switching to alternative medication, and the potential impact of age, gender and choice of initial drug. Methods: Data on prescription drug use in Canada were retrieved from the IMS Brogan public and private prescription claims databases. Medication usage was tracked for four years following an index claim. The primary endpoint was the number of days from index claim to discontinuation of medication. Secondary endpoints were the number of days on first-line therapy before switching. Descriptive results were evaluated using univariate (Kaplan-Meier) and multivariate (Cox proportional hazards) models. Results: Data were available for 31,754 patients. Approximately 91% discontinued OAB medication within the four-year follow-up period. The discontinuation rate was similar between men and women. The risk of discontinuation in patients ≥75 years was only slightly higher than that in patients aged 40-64 years (hazard ratio of 1.08) and was lower than in those aged 65-74 years. Retention when oxybutynin was the initial drug was lower than with most of the other antimuscarinics. Only 12.5% of patients changed OAB medication during the 4-year period. Women were more likely than men to switch from first-line or second-line treatment. Conclusions: Discontinuation of initial antimuscarinic therapy was high. Compared with oxybutynin, several alternative antimuscarinics offered lower risks of discontinuation. The majority of patients had no trial of second-line treatment.

Healthcare resource use and costs of privately insured patients who switch, discontinue, or persist on anti-muscarinic therapy for overactive bladder.

OBJECTIVES: To compare the healthcare costs of patients with overactive bladder (OAB) who switch vs persist on anti-muscarinic agents (AMs), describe resource use and costs among OAB patients who discontinue AMs, and assess factors associated with persisting vs switching or discontinuing. METHODS: OAB patients initiating an AM between January 1, 2007 and March 31, 2012 were identified from a claims database of US privately insured beneficiaries (n ≈ 16 million) and required to have no AM claims in the 12 months before AM initiation (baseline period). Patients were classified as persisters, switchers, or discontinuers, and assigned a study index date based on their AM use in the 6 months following initiation. Baseline characteristics, resource use, and costs were compared between persisters and the other groups. Resource use and costs in the 1 month before and 6 months after the study index date (for switchers, the date of index AM switching; for persisters, a randomly assigned date to reflect the distribution of the time from AM initiation to switching among switchers) were also compared between persisters and switchers in unadjusted and adjusted analyses. Factors associated with persisting vs switching or discontinuing were assessed. RESULTS: After controlling for baseline characteristics and costs, persisters vs switchers had significantly lower all-cause and OAB-related costs in both the month before (all-cause $1222 vs $1759, OAB-related $142 vs $170) and 6 months after the study index date (all-cause $7017 vs $8806, OAB-related $642 vs $797). Factors associated with switching or discontinuing vs persisting included index AM, younger age, and history of UTI. CONCLUSION: A large proportion of OAB patients discontinue or switch AMs shortly after initiation, and switching is associated with higher costs.

Direct and indirect costs of patients treated with extended-release oxymorphone HCl or controlled-release oxycodone HCl.

OBJECTIVE: Compare direct and indirect costs of oxymorphone extended-release ('oxymorphone') and oxycodone controlled-release ('oxycodone') users. METHODS: Patients, aged 18+, with ≥1 claim for oxymorphone/oxycodone, Q2:2006-Q4:2009, were selected from a de-identified private payer claims database and observed from the first such claim ('index date') until the earliest of: use of comparator drug; end of continuous eligibility; 12 months ('study period'). Patients with claims for any formulation of the comparator drug during the first 30 days of the study period were excluded. Direct (medical and drug) costs paid by private insurers were reported for patients aged 18-64 (n = 8354) and 65+(n = 3515), as well as sub-sets without cancer (n = 7090 and n = 2444, respectively). Indirect costs (medically-related absenteeism and disability) were reported for all employees, aged 18-64 (n = 1313), and employees without cancer (n = 1146). Multivariate models were used to estimate risk-adjusted costs controlling for patient characteristics. RESULTS: Oxymorphone users, aged 18-64, had lower drug costs ($693 vs $763, p = 0.0035) and similar medical costs ($1875 vs $1976, p = 0.3570) per patient-month compared with oxycodone users (mean follow-up 236 and 280 days, respectively). Indirect costs were not different ($662 vs $670, p = 0.9370). Oxymorphone users, aged 65+, had similar Medicare supplemental drug costs ($533 vs $588, p = 0.0840) and lower medical costs ($459 vs $747, p < 0.0001). Results were comparable for subsets without cancer. LIMITATIONS: Patients with concomitant use of oxymorphone and oxycodone were excluded. CONCLUSIONS: Oxymorphone users incur lower risk-adjusted costs in several cost categories, compared with oxycodone users, and no higher costs in any of the examined categories.

A Comparison of Daily Average Consumption Of Oxycodone Controlled Release (OxyContin CR) And Oxymorphone Extended Release (Opana ER) In Patients With Low Back Pain.

OBJECTIVE: Our goal was to examine the daily average consumption (DACON) of oxycodone controlled-release tablets (OxyContin CR)and oxymorphone extended-release tablets (Opana ER) in patients with low back pain. STUDY DESIGN: An observational, retrospective cohort study enrolled patients with multiple prescriptions for oxycodone CR or oxymorphone ER tablets. These patients also had International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for low back pain. Pharmacy prescription medication claims data were obtained from a large commercially insured health plan in the U.S. Mean daily consumption was calculated for a 90-day period. METHODS: We used descriptive statistics to evaluate patient demographics and health plan characteristics. Univariate analyses were used to examine the data as observed. A generalized linear model with a gamma distribution and log-link function provided a sensitivity measure, adjusting for heterogeneity among patients and the skewed nature of the DACON variable. RESULTS: A total of 4,023 patients received oxycodone CR, and 374 patients received oxymorphone ER. The mean age of patients (standard deviation, SD) was 49.0 (11.6) years for oxycodone CR and 47.3 (10.6) years for oxymorphone ER. DACON of oxycodone CR was 3.2 tablets per day, and DACON of oxymorphone ER was 2.7 tablets per day (P < 0.01). Utilization of maximum-strength tablets of oxycodone CR 80 mg was 3.9 tablets per day, which was significantly higher, by one tablet per day, than the utilization of equipotent oxymorphone ER maximum-strength tablets of 40 mg at 2.9 tablets per day (P < 0.01). CONCLUSION: The use of oxycodone CR, measured as mean daily consumption over a 90-day period, was significantly higher than that for oxymorphone ER in these patients, a finding that could have financial implications for health care systems.

Scheduled short-term prevention with frovatriptan for migraine occurring exclusively in association with menstruation.

OBJECTIVE: This post hoc subgroup analysis evaluated scheduled short-term preventive frovatriptan therapy for women with migraine occurring exclusively in association with menstruation (occurring day -2 to +3; day 1 = menses start, no migraines outside this window). BACKGROUND: A previously published randomized, double-blind, placebo-controlled 3-way crossover trial assessed the efficacy and safety of a scheduled 6-day preventive regimen with frovatriptan for the treatment of menstrual migraine; the study population included women experiencing both menstrual and non-menstrual migraine and women experiencing only menstrual migraine. METHODS: Women received each treatment (placebo, frovatriptan 2.5 mg once daily, and frovatriptan 2.5 mg twice daily) once over 3 perimenstrual periods in randomized sequence. For this subset analysis, screening questions were used to identify women with migraine occurring exclusively in association with menstruation. Efficacy was evaluated by occurrence and severity of migraine, functional impairment, and rescue medication use. Adverse events and tolerability were also assessed. RESULTS: Among 179 patients, the mean age (SD) was 37.3 (7.7) years and mean menstrual migraine history was 10.6 (8.7) years. Significantly fewer women experienced menstrual migraine during treatment with frovatriptan twice daily (37.7%, P < .001) or once daily (51.3%, P = .002) than during treatment with placebo (67.1%); a significant dose response was noted (P = .01, twice daily vs once daily). Significant treatment differences were also found for several secondary endpoints, but the data from this post hoc analysis must be interpreted with caution. Frovatriptan was well tolerated and most adverse events were mild or moderate and similar to those reported with the acute treatment of migraine with frovatriptan; the most common adverse events were nausea, dizziness, and headache. CONCLUSIONS: Scheduled short-term preventive frovatriptan therapy effectively reduced the occurrence of menstrual migraine in women with attacks occurring exclusively in association with menstruation.