Comparison of Healthcare Costs for Women with Treated Versus Untreated Vasomotor Symptoms Due to Menopause.

INTRODUCTION: The study objective was to estimate all-cause healthcare resource utilization (HCRU) and medical and pharmacy costs for women with treated versus untreated vasomotor symptoms (VMS) due to menopause. METHODS: A retrospective study was conducted using US claims data from Optum Research Database (study period: January 1, 2012-February 29, 2020). Women aged 40-63 years with a VMS diagnosis claim and ≥ 12 and ≥ 18 months of continuous enrollment during baseline and follow-up periods, respectively, were included. Women treated for VMS were propensity score matched 1:1 to untreated controls with VMS. Standardized differences (SDIFF) ≥ 10% were considered meaningful. A generalized linear model (gamma distribution, log link, robust standard errors) estimated the total cost of care ratio. Subgroup analyses of on- and off-label treatment costs were conducted. RESULTS: Of 117,582 women diagnosed with VMS, 20.5% initiated VMS treatment and 79.5% had no treatment. Treated women (n = 24,057) were matched to untreated VMS controls. There were no differences in HCRU at follow-up (SDIFF < 10%). Pharmacy ($487 vs $320, SDIFF 28.4%) and total ($1803 vs $1536, SDIFF 12.6%) costs were higher in the treated cohort. Total costs were 7% higher in the treated cohort (total cost ratio 1.07, 95% CI 1.05-1.10, P < 0.001). The on-label treatment pharmacy costs ($546 versus $315, SDIFF 38.6%) were higher in the treated cohort. Off-label treatment had higher medical costs ($1393 versus $1201, SDIFF 10.4%). CONCLUSIONS: Most women with VMS due to menopause were not treated within 6 months following diagnosis. While both on- and off-label treatment increased the total cost of care compared with untreated controls, those increases were modest in magnitude and should not impede treatment for women who report symptom improvement as a result of treatment.

Association of menopausal vasomotor symptom severity with sleep and work impairments: a US survey.

OBJECTIVE: Menopausal vasomotor symptoms commonly disrupt sleep and affect daytime productivity. This online survey evaluated associations between vasomotor symptom severity and perceived sleep quality and work productivity. METHODS: Participants were perimenopausal or postmenopausal US women aged 40 to 65 years with ≥14 vasomotor symptom episodes per week for ≥1 week in the past month. The women, who were recruited from Dynata panels via email invitation and categorized by vasomotor symptom severity based on the Menopause Rating Scale, were surveyed about sleep and work productivity and completed the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b (primary outcome) and Sleep-Related Impairment Short Form 8a, Pittsburgh Sleep Quality Index, and Work Productivity and Activity Impairment questionnaire. RESULTS: Among 619 respondents (mean age, 53 y; White, 91%; perimenopausal, 34%; postmenopausal, 66%; 57.5% were never treated for vasomotor symptoms), vasomotor symptoms were mild in 88, moderate in 266, and severe in 265. A majority (58% overall) were employed, including 64.8%, 49.6%, and 64.2% of women with mild, moderate, and severe VMS, respectively. Of the 90.8% who reported that vasomotor symptoms affect sleep (81.8%, 86.8%, and 97.7% of those with mild, moderate, and severe VMS), 83.1% reported sleep-related changes in productivity (75.0%, 73.2%, and 94.2%, respectively). Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b mean T scores in the mild (T score, 53.5), moderate (57.3), and severe (59.8) VMS cohorts indicated more sleep disturbance than in the general population (T score, 50; overall P < 0.001 before and after controlling for confounding variables). Sleep-Related Impairment 8a results were similar. Vasomotor symptom severity was positively associated with Pittsburgh Sleep Quality Index mean scores, presenteeism, absenteeism, overall work impairment, and impairment in general activities. CONCLUSIONS: Greater vasomotor symptom severity was associated with more sleep disturbance, more sleep-related impairment, worse sleep quality, and greater impairment in daytime activities and work productivity.

Assessment of women's treatment preferences for vasomotor symptoms due to menopause.

BACKGROUND: Several therapies for vasomotor symptoms (VMS) due to menopause are available. Treatment preferences and willingness-to-pay for VMS treatment among US women with VMS were evaluated. METHODS: An online survey of women with perimenopausal or postmenopausal VMS was conducted (3/15/21-4/23/21). A discrete choice experiment quantified the impact of 7 treatment attributes on VMS treatment choice: VMS frequency/severity reduction, sleep improvement, risk of breast cancer/cardiovascular events in 6 years, risk of short-term side effects, and out-of-pocket costs. Preference weights (PWs) with 95% confidence intervals (CIs) were estimated and reported. RESULTS: Among 467 women, 86.5% and 87.8% reported moderate to very severe VMS and sleep problems during the preceding month, respectively. Sleep improvement (PW: 0.843; 95% CI: 0.721, 0.965) and reduction in VMS frequency (PW: 0.658; 95% CI: 0.520, 0.796) and severity (PW: 0.628; 95% CI: 0.500, 0.756) most influenced treatment preference; risk of cardiovascular events (PW: 0.150; 95% CI: 0.069, 0.232) or breast cancer (PW: 0.401; 95% CI: 0.306, 0.496) in 6 years had lesser effect. Willingness-to-pay was an additional $35-$46/month for substantially improved sleep, 80% VMS frequency reduction, and reduction from severe to mild VMS. CONCLUSIONS: Sleep improvement and reductions in VMS frequency/severity were the most important treatment attributes.

Hormone and non-hormone treatments are available to reduce vasomotor symptoms (hot flashes and night sweats) due to menopause. We conducted an online survey of 467 women with moderate to very severe vasomotor symptoms during perimenopause or postmenopause to learn what treatment attributes are most important to women when selecting from among the available therapies and how much women were willing to pay for the attributes. Women were shown 14 cards, each with a side-by-side comparison of 2 treatments with varying descriptions of the following 7 treatment attributes: reduction in frequency of vasomotor symptoms, reduction in severity of vasomotor symptoms, improvement in sleep, risk of breast cancer in 6 years, risk of cardiovascular events in 6 years, risk of short-term side effects, and out-of-pocket costs. Women picked their preferred treatment on each card. Results showed that improvement in sleep was the most important attribute to women, and they were willing to pay an extra $46/month for a treatment that substantially improved sleep. The next most important attributes were reduction in frequency and reduction in severity of vasomotor symptoms. Women were willing to pay $36/month more for a treatment that reduced symptom frequency by 80% compared with one that reduced frequency by 50%, and they were willing to pay $35/month more for treatment that reduced symptoms from severe to mild compared with one that did not reduce symptom severity. These results may help guide development of new treatment options and may help physicians recommend treatments that best fit women's preferences.

Association between vasomotor symptom frequency and weight gain in the Study of Women's Health Across the Nation.

OBJECTIVE: The menopause transition is associated with weight gain in women. We examined whether changes in vasomotor symptom (VMS) frequency precede weight changes. METHODS: This longitudinal retrospective analysis included data from the multisite, multiethnic Study of Women's Health Across the Nation. Women in premenopause or perimenopause aged 42 to 52 years at baseline self-reported VMS frequency (hot flashes/night sweats) and sleep problems at up to 10 annual visits. Menopause status, weight, body mass index, and waist circumference were compared across visits. The primary objective was to measure the association between VMS frequency and weight gain using a lagged approach with first-difference regression models. Secondary objectives were to statistically quantify mediation by sleep problems and moderation by menopause status and explore the association between cumulative, 10-year VMS exposure and long-term weight gain. RESULTS: The primary analysis sample included 2,361 participants (12,030 visits; 1995-2008). Increased VMS frequency across visits was associated with subsequently increased weight (0.24 kg), body mass index (0.08 kg/m 2 ), and waist circumference (0.20 cm). Cumulative exposure to a high frequency of VMS (≥6 d/2 wk) over 10 consecutive annual visits was associated with increases in weight measures, including a 3.0-cm increase in waist circumference. Contemporaneous sleep problems mediated no more than 27% of waist circumference increases. Menopause status was not a consistent moderator. CONCLUSIONS: This study demonstrates that increases in VMS, onset of a high frequency of VMS, and persistent VMS symptoms over time may precede weight gain in women.

Novel presynaptic assay system revealed that metformin ameliorates exaggerated synaptic release and Munc18-1 accumulation in presynapses of neurons from Fragile X syndrome mouse model.

Fragile X syndrome (FXS) is a developmental disorder characterized by intellectual disability and autistic-like behaviors. These symptoms are supposed to result from dysregulated translation in pre- and postsynapses, resulting in aberrant synaptic plasticity. Although most drug development research on FXS has focused on aberrant postsynaptic functions by excess translation in postsynapses, the effect of drug candidates on FXS in presynaptic release is largely unclear. In this report, we developed a novel assay system using neuron ball culture with beads to induce presynapse formation, allowing for the analysis of presynaptic phenotypes, including presynaptic release. Metformin, which is shown to rescue core phenotypes in FXS mouse model by normalizing dysregulated translation, ameliorated the exaggerated presynaptic release of neurons of FXS model mouse using this assay system. Furthermore, metformin suppressed the excess accumulation of the active zone protein Munc18-1, which is supposed to be locally translated in presynapses. These results suggest that metformin rescues both postsynaptic and presynaptic phenotypes by inhibiting excess translation in FXS neurons.

Practice patterns and perspectives regarding treatment for symptoms of menopause: qualitative interviews with US health care providers.

OBJECTIVE: To document health care providers' views regarding treatments for symptoms associated with menopause and discussions with patients about symptoms and treatment decisions. Results informed development of a data collection form for a retrospective medical record review (reported separately). METHODS: Registered US gynecologists or primary care providers from all US regions were identified from local association directories and an in-house database and were invited to participate in a qualitative interview if they consulted with three or more patients per week presenting with menopausal symptoms. Participants provided demographic data, information about patients' symptoms, and health care provider and patient views on prescription and nonprescription therapies. Key concepts/themes from interviews were identified. RESULTS: Participating health care providers (10 gynecologists, 10 primary care providers) agreed there are effective treatment options for menopausal symptoms, particularly vasomotor symptoms and vaginal dryness and/or atrophy. Health care providers reported that treatment was generally dictated by symptoms that interfered with quality of life and/or daily activities, although patients often had symptoms for months before presentation. All health care providers said they prescribe hormone and/or nonhormone therapies for treatment of menopausal symptoms; half stated that they typically inquire about patients' nonprescription therapy use, and 45% recommend specific nonprescription therapies. The most commonly cited barriers to initiation of any therapy for menopausal symptoms were patient concerns about risks and financial considerations (ie, insurance or cost). CONCLUSIONS: US health care providers reported prescribing therapies for menopausal symptoms and noted that these therapies were perceived as generally effective; however, barriers to initiation of prescription therapy exist, and new treatment options are needed.

Treatment and resource utilization for menopausal symptoms in the United States: a retrospective review of real-world evidence from US electronic health records.

OBJECTIVE: The aim of this study was to generate real-world evidence documenting use of prescription and nonprescription therapies recorded by health care providers for women experiencing vasomotor symptoms (VMS) associated with menopause. METHODS: This noninterventional, retrospective, observational cohort study used data from US patient medical records. Participating health care providers were gynecologists, internal medicine/family physicians, or advanced practice providers who typically saw three or more women per week presenting with menopausal symptoms and could identify eligible medical records; providers were recruited from local medical association directories and from listings from previously conducted research. Eligible women presented January 2016 through December 2019, were 40 to 60 years of age, and reported experiencing bothersome hot flashes at least twice within 24 hours. RESULTS: A total of 283 health care providers provided data for 1,016 women. The most common symptoms at initial presentation were hot flashes (91.2%), sleep problems (49.9%), and vaginal dryness (47.0%). At least one therapy for menopausal symptoms was recorded for 883 women (86.9%), and 611 (60.1%) had documentation of prescription medication, most commonly hormone therapy (70.4%). Nearly 40% of women had no prescription medication documented, and approximately 13% had no therapy documented. Despite experiencing bothersome menopausal symptoms, approximately 50% delayed seeking care for more than 6 months. Women had a mean of 2.1 (SD, 2.0) office visits related to menopause from initial presentation to completion of review, and health care resource utilization did not vary by treatment status. Subgroup analyses indicated nominal differences in treatment use across ethnic groups and varying prescribing patterns for menopausal symptoms by practitioner type and US region. CONCLUSIONS: A high proportion of women with VMS remain untreated even when experiencing bothersome symptoms of menopause. Improved management of VMS is required to provide relief from the symptoms effectively and safely.

A 12-Year Retrospective Study of the Prevalence of Anticholinergic Polypharmacy and Associated Outcomes Among Medicare Patients with Overactive Bladder in the USA.

BACKGROUND AND OBJECTIVE: Antimuscarinics, drugs with anticholinergic properties, are frequently prescribed for overactive bladder, and anticholinergic burden is associated with adverse events. The "Polypharmacy: Use of Multiple Anticholinergic Medications in Older Adults" (Poly-ACH) measure was developed by the Pharmacy Quality Alliance and is used by the Centers for Medicare and Medicaid Services. Using the Poly-ACH measure, we assessed the prevalence of anticholinergic polypharmacy among Medicare patients in the USA with overactive bladder and determined associations between polypharmacy and medical conditions, care, and spending. METHODS: This was a retrospective cohort study of Medicare beneficiaries with overactive bladder (coverage period: 2006-2017). Anticholinergic polypharmacy, measured by the Poly-ACH, was defined as concurrent use of two or more anticholinergics, each with two or more prescription claims on different dates of service for ≥ 30 cumulative days. Change in annual frequency of anticholinergic polypharmacy was assessed using logistic regression. Associations between anticholinergic polypharmacy over 3 years and falls, fractures, mental status, and medical care spending were assessed with longitudinal regression models. RESULTS: In total, 226,712 patients contributed 940,201 person-years of follow-up after overactive bladder diagnosis. The share of patients meeting the Poly-ACH definition was 3.3% in 2006 and 1.7% in 2017. Women and nursing home residents had higher risks of anticholinergic polypharmacy. Having 1 year or more of positive Poly-ACH status in the 3 years prior was associated with higher rates of all outcomes. CONCLUSIONS: Anticholinergic polypharmacy was uncommon among older adults with overactive bladder. Prevalence was higher among women and nursing home residents, and it was associated with negative outcomes, highlighting potential longitudinal implications of anticholinergic burden.

Impact of sleep disturbances on employment and work productivity among midlife women in the US SWAN database: a brief report.

OBJECTIVE: Menopause is associated with an increased prevalence of sleep difficulties. We evaluated the economic burden of sleep disturbances among working midlife women. METHODS: This retrospective, longitudinal cohort study collected data from the US Study of Women's Health Across the Nation (SWAN) database of women age 42-52 years at enrollment. We assessed the association between sleep disturbances (trouble falling asleep, waking early, or nocturnal awakenings) and workplace productivity (employment [yes/no] and work hours/wk) for women who were employed at the baseline visit and had ≥1 follow-up visit. We estimated overall economic burden by multiplying changes in productivity by median age-specific hourly US wages. Each woman's data were compared from visit to visit and were excluded after the first observed unemployment. Regression analysis was used to estimate associations between changes in sleep and changes in workplace productivity while controlling for relevant characteristics that varied over time. RESULTS: The analysis included 2,489 working women (19,707 visits); 31% became unemployed during follow-up. Risk of unemployment was 31% higher for women with versus without new-onset sleep disturbances (P  = 0.0474). Onset of sleep disturbances was associated with a 0.44-0.57 hours/wk reduction in work time (not significant). Using the more conservative reduction (0.44 h), sleep problems were associated with an annual loss of $517 to $524 per woman and $2.2 billion/yr in lost productivity among women age 42-64 nationwide. CONCLUSIONS: New-onset sleep problems in midlife women are associated with significant increases in risk of unemployment and ∼$2 billion/yr in lost productivity nationwide.

Video Summary : http://links.lww.com/MENO/A798 .

Higher Resource Utilization and Costs in Long-Term Nursing Home Residents With Overactive Bladder: A Retrospective Study of Medicare Beneficiaries.

OBJECTIVES: To determine the all-cause health care resource utilization and costs among long-term nursing home (LTNH) residents with and without overactive bladder (OAB). DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Minimum Data Set (MDS)-linked Medicare Part A, B, and D claims data from 2013 to 2015 were analyzed. LTNH residents aged 65 years or older with a diagnosis of OAB (n = 216,731) were propensity score matched with LTNH residents without OAB (n = 300,327) (non-OAB cohort). METHODS: We measured health care resource utilization and costs associated with OAB by setting (inpatient, outpatient, emergency department, or prescription) during the 6 months following nursing home admission. Descriptive and multivariate (negative binomial for health care resource utilization and 2-part model for costs) analyses were performed to examine the health care resource utilization and costs among LTNH residents with and without OAB. The annual cost attributed to OAB was calculated as the difference between total annual OAB costs and total annual non-OAB costs. RESULTS: A total of 214,505 patients were included in each matched cohort. Across all health care resource categories, LTNH residents with OAB had higher health care resource utilization and costs compared to the non-OAB cohort (all P < .001). The mean annual direct total cost was $57,984 in the OAB cohort compared with $54,285 in the non-OAB cohort. The annual cost of OAB in nursing homes was estimated at $793 million. Adjusted analyses revealed that the OAB cohort was 9% more likely to have hospitalization and emergency department visits, 15% more likely to have outpatient visits, 27% more likely to have physician visits, and 12% more likely to have prescription counts compared with the non-OAB cohort. CONCLUSIONS AND IMPLICATIONS: The study findings suggest that LTNH residents with OAB have significantly more health care resource utilization compared with patients without OAB. These results provide health care decision makers with recent estimates of the burden of OAB in LTNH to assist them with resource planning.

Increased Healthcare Resource Utilization and Direct and Indirect Costs in Patients with Depression and Comorbid Overactive Bladder: Evidence From a Retrospective, Matched Case-Control Cohort Analysis.

INTRODUCTION: This study sought to compare healthcare resource utilization (HCRU), costs, and workplace productivity among patients with depression, with and without overactive bladder (OAB). METHODS: This retrospective, case-control cohort analysis compares HCRU, costs, and workplace productivity among propensity score matched patients with depression and OAB (case cohort) and patients with depression without OAB (control cohort). Patients were aged 18 years or older, insured/on Medicare, and had diagnosed depression and an antidepressant medication claim pre index. First OAB-related event was index for cases; controls were assigned a proxy (study period 12 months). Comparisons of HCRU and costs and regression models assessed the relationship between OAB and costs. For the workplace productivity subset analyses cases and controls were balanced on baseline covariates for the short-term disability analyses but as they were unbalanced for the absentee analyses, multivariate regression analyses were used for this subset. RESULTS: The study criteria were met by 39,085 cases and 308,736 controls, from which, 37,997 patients were successfully matched 1:1 (mean age 55 years; 81% female). Most depression-related HCRU measures were similar across cohorts; however, outpatient visits, ER visits, and number of unique depression medications were significantly higher (all p < 0.05) among cases. Cases also had 13% higher total depression-related costs (p < 0.0001). Total mean (standard deviation [SD]) depression-related costs were $1796 ($4235) for cases versus $1597 ($3863) for controls (p < 0.0001). For workplace productivity (absentee data: cases [n = 686], controls [n = 642]; short-term disability data: cases [n = 4395], controls [n = 4433]) absentee outcomes were similar across cohorts. However, a higher percentage of cases used short-term disability benefits compared to controls (21.3% versus 16.9%; p < 0.0001) and cases experienced more case days (11.0 versus 8.6 mean days) and received higher mean payments than controls ($1226 versus $1033; p < 0.0001) in this subset. CONCLUSIONS: OAB was associated with 13% higher depression-related costs and 4.4% more cases used short-term disability benefits.

Treatment patterns and costs among patients with OAB treated with combination oral therapy, sacral nerve stimulation, percutaneous tibial nerve stimulation, or onabotulinumtoxinA in the United States.

INTRODUCTION: Treatment patterns and costs were characterized among patients with overactive bladder (OAB) receiving later-line target therapies (combination mirabegron/antimuscarinic, sacral nerve stimulation [SNS], percutaneous tibial nerve stimulation [PTNS], or onabotulinumtoxinA). METHODS: In a retrospective cohort study using 2013 to 2017 MarketScan databases, two partially overlapping cohorts of adults with OAB ("IPT cohort": patients with incident OAB pharmacotherapy use; "ITT cohort," incident target therapy) with continuous enrollment were identified; first use was index. Demographic characteristics, treatment patterns and costs over the 24-month follow-up period were summarized. Crude mean (standard deviation [SD]) OAB-specific (assessed by OAB diagnostic code or pharmaceutical dispensation record) costs were estimated according to target therapy. RESULTS: The IPT cohort comprised 54 066 individuals (mean [SD] age 58.5 [15.0] years; 76% female), the ITT cohort, 1662 individuals (mean [SD] age 62.8 [14.9] years; 83% female). Seventeen percent of the IPT cohort were treated with subsequent line(s) of therapy after index therapy; among those, 73% received antimuscarinics, 23% mirabegron, and 1.4% a target therapy. For the ITT cohort, 32% were initially treated with SNS, 27% with onabotulinumtoxinA, 26% with combination mirabegron/antimuscarinic, and 15% with PTNS. Subsequently, one-third of this cohort received additional therapies. Mean (SD) costs were lowest among patients receiving index therapy PTNS ($6959 [$7533]) and highest for SNS ($29 702 [$26 802]). CONCLUSIONS: Costs for SNS over 24 months are substantially higher than other treatments. A treatment patterns analysis indicates that oral therapies predominate; first-line combination therapy is common in the ITT cohort and uptake of oral therapy after procedural options is substantial.

Antimuscarinic Discontinuation in Patients with Overactive Bladder in Nursing Homes: A Retrospective Study of Medicare Beneficiaries.

INTRODUCTION: Although antimuscarinics form the first-line therapy in overactive bladder (OAB), little is known regarding antimuscarinic discontinuation among OAB patients in nursing homes. This study examined treatment patterns and predictors of antimuscarinic discontinuation among long-term nursing home (LTNH) residents with OAB. METHODS: The study cohort included LTNH residents (defined as residents staying ≥ 101 consecutive days) from the Minimum Data Set linked 2013-2015 Medicare claims data. Patients with OAB were defined by OAB-related claims and medication codes. Treatment patterns and discontinuation (medication gap ≥ 30 days) were characterized by examining OAB-specific antimuscarinics prescribed during LTNH stays. The Andersen Behavioral Model was used to identify predisposing, enabling and need factors that predict discontinuation. Kaplan-Meier curves and multivariable Cox proportional hazards regression model were used to assess the unadjusted and adjusted times to discontinuation, respectively, among different antimuscarinics. RESULTS: The mean age of the study cohort (n = 11,012) was 81.6 years (± 8.5), 74.6% were female, and 89.8% were non-Hispanic White. The mean duration of nursing home stay was 530.1 (± 268.4) days. The most commonly prescribed OAB-specific antimuscarinic was oxybutynin (69.8%). Overall, 66.5% of the study cohort discontinued the index antimuscarinic. Multivariable Cox PH regression analysis revealed that compared to LTNH residents who initiated treatment with oxybutynin, treatment discontinuation was lower with solifenacin or fesoterodin and discontinuation was more frequent when treatment was initiated with tolterodine, darifenacin or trospium compared with oxybutynin. In addition, several need factors (comorbidities, medication use and anticholinergic burden, etc.) were associated with antimuscarinic discontinuation. CONCLUSION: About  two-thirds of LTNH residents with OAB discontinued their index antimuscarinic during their nursing home stay. There was significant variation in discontinuation based on the index antimuscarinic agent with lowest risk of discontiuation with solifenacin and fesoterodin. Concerted efforts to optimize antimuscarinic use are needed to improve the management of OAB in nursing homes.

Cost-effectiveness model for a hypothetical monotherapy vs standard of care in adult patients with treatment-resistant depression.

BACKGROUND: Patients with treatment-resistant major depressive disorder (TRD) have limited treatment options. We developed an early stage cost-effectiveness model of TRD to explore the potential value of a hypothetical monotherapy relative to the standard of care (SOC). The relative impacts of the monotherapy's three differentiating features over SOC are explored: efficacy advantage, tolerability advantage, and price premium. METHODS: We adapted an existing economic model of TRD to evaluate the cost-effectiveness of a hypothetical monotherapy for TRD with a 25% efficacy advantage, a 10% tolerability advantage, and a 50% price premium over SOC (selective serotonin reuptake inhibitor plus atypical antipsychotics [SSRI + AAP]). The model is a hybrid of a decision tree that captures patients' outcomes after an 8-week acute treatment phase and a Markov model that simulates patients' depression course through a 10-month maintenance phase. Sensitivity (deterministic and probabilistic) and scenario analyses were conducted to characterize the relative impacts of the monotherapy's three differentiating features over SOC. RESULTS: Over the 12-month time horizon, the hypothetical monotherapy is shown to dominate SOC; it generates lower costs and higher quality-adjusted life years in comparison to SSRI + AAP. Sensitivity and scenario analyses showed that this dominance depends largely on the monotherapy's efficacy and tolerability advantages over SOC. Specifically, a monotherapy with ≥ 12% efficacy or ≥70% tolerability advantage (and a 50% price premium) will always be superior to SSRI + AAP. Between these two extremes, most profiles, nonetheless, generate incremental cost-utility ratios for the monotherapy, which fall below common payer willingness-to-pay thresholds. CONCLUSION: Our adaptation of an existing economic model of TRD provides a flexible platform for researchers to evaluate the efficacy/tolerability improvements required for a successful new TRD product and for decision-makers to assess the cost-effectiveness impact of uncertainties inherent in early stage product development in TRD.

Treatment and comorbidities of multiple sclerosis in an employed population in Japan: analysis of health claims data.

AIM: Use real-world data to investigate the treatment, comorbidities and prevalence of multiple sclerosis (MS) in an employed Japanese population. METHODS: Data from the Japanese Medical Data Center health insurance claims database were analyzed (January 2005-November 2014). Patients with claims associated with an MS diagnosis were identified (n = 494) and comorbidities and prescribed treatments were investigated. MS prevalence within the database was calculated for each calendar year (2011-2013) Results: IFN-ß and prednisolone were the most commonly prescribed treatments. Common comorbidities included astigmatism and gastric ulcer. Within the database, MS prevalence increased from 0.015 to 0.016%. CONCLUSION: MS prevalence increased from 2011 to 2013. Some comorbidities were considered unrelated to MS owing to how physicians use disease codes for reimbursement.

Serum Uric Acid and the Risk of Incident and Recurrent Gout: A Systematic Review.

OBJECTIVE: Lowering serum uric acid (SUA) levels can essentially cure gout; however, this is not widely practiced. To summarize epidemiologic evidence related to this causal link, we conducted a systematic review of the published literature reporting the association between SUA level and incident and recurrent gout (i.e., gout flares). METHODS: We systematically searched Medline, EMBASE, and the Cochrane Database of Systematic Reviews using separate search strategies for incident gout and recurrent gout. We screened 646 abstracts to identify 8 eligible articles reporting gout incidence and 913 abstracts to identify 18 articles reporting recurrent gout. RESULTS: For both gout incidence and recurrence, a graded trend was observed where the risk was increased with higher SUA levels. Gout incidence rates per 1000 person-years from population-based studies ranged from 0.8 (SUA ≤ 6 mg/dl) to 70.2 cases (SUA ≥ 10 mg/dl). Recurrent gout risk in clinical cohorts ranged from 12% (SUA ≤ 6 mg/dl) to 61% (SUA ≥ 9 mg/dl) among those receiving urate-lowering therapy (ULT), and 3.7% (SUA 6-7 mg/dl) to 61% (SUA > 9.3 mg/dl) after successful ULT. Retrospective database studies also showed a graded relationship, although the strength of the association was weaker. Studies reporting mean flares or time-to-flare according to SUA showed similar findings. CONCLUSION: This systematic review confirms that higher SUA levels are associated with increased risk of incident and recurrent gout in a graded manner. Although few prospective cohorts have evaluated incident and recurrent gout according to SUA, the existing evidence underscores the need to treat to SUA targets, as recommended by the American College of Rheumatology and the European League Against Rheumatism.

Serum uric acid levels and the risk of flares among gout patients in a US managed care setting.

OBJECTIVE: Serum uric acid (sUA) levels are causally associated with the risk of gout flares. Our aim was to assess the magnitude of the association and time to first flare among patients in a managed care setting. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using administrative claims data from a large US health plan. Patients were required to have evidence of gout based on medical and pharmacy claims between January 2009 and April 2012. The 12 months prior to the index gout claim were used to assess baseline sUA levels; risk of gout flares, stratified by baseline sUA levels, was examined for 2 years post-index. Risk of flare was modeled with Cox proportional hazards; time to first flare was assessed by Kaplan-Meier. RESULTS: We identified 18,008 patients with gout and available baseline SUA levels (mg/dL). The hazard ratios for the risk of gout flares compared with sUA <5.0 were: 1.17 for sUA 5.0 to <6.0; 1.69 for sUA 6.0 to <7.0; 2.16 for sUA 7.0 to <8.0; 2.87 for sUA 8.0 to <9.0; and 3.85 for sUA ≥9.0 (all p < .001 except for sUA 5.0 to <6.0 cohort). The time to first flare was shorter for cohorts with higher baseline sUA levels. CONCLUSION: These findings confirm that higher sUA levels are associated with an increased risk of gout flares in a dose-response manner over 2 years. This data supports the need to treat to sUA target levels as recommended by recent gout care guidelines. Claims-based algorithms were used to identify gout flares; although this would not be expected to influence estimates of risk by sUA level, there may have been over- or under-estimation of the incidence of flares.

The Budget Impact of Increased Use of Febuxostat in the Management of Gout: A US Health Plan Managed Care Pharmacy and Medical Costs Perspective.

PURPOSE: Gout is a chronic disease characterized by the deposition of urate crystals in the joints and throughout the body, caused by an excess burden of serum uric acid (sUA). The study estimates pharmacy and medical cost budgetary impacts of wider adoption by US payers of febuxostat, a urate-lowering therapy (ULT) for the treatment of gout. METHODS: A US payer-perspective budget impact model followed ULT patients from a 1,000,000-member plan over 3 years. The current market share scenario, febuxostat (6%) and ULT allopurinol (94%), was compared with an 18% febuxostat market share. Data were implemented from randomized controlled trials, census and epidemiologic studies, and real-world database analyses. An innovation was the inclusion of gout-related chronic kidney disease costs. Cost results were estimated as annual and cumulative incremental costs, expressed as total costs, cost per member per month, and cost per treated member per month. Clinical results were also estimated. FINDINGS: Increasing the febuxostat market share resulted in a 6.3% increase in patients achieving the sUA target level of <6.0 mg/dL and a 1.4% reduction in gout flares during the 3-year period. Total cost increased 1.4%, with a 49.9% increase in ULT costs, a 1.4% reduction in flare costs, a 1.2% reduction in chronic kidney disease costs, and a 2.8% reduction in gout care costs. The cumulative incremental costs were $1,307,425 in the first year, $1,939,016 through the second year, and $2,092,744 through the third year. By the third year, savings in medical costs offset most of the increase in treatment costs. Impacts on cumulative cost per member per month and cumulative cost per treated member per month followed the same pattern, with the highest impact in the first year and cumulative impacts declining during the 3-year period. The cumulative cost per member per month impact was estimated as $0.109, $0.081, and $0.058 and the cumulative cost per treated member per month impact was estimated as $12.416, $9.207, and $6.625 in the first year, through the second year, and through the third year, respectively. IMPLICATIONS: Expanding the febuxostat market share would result in improved clinical outcomes, but with an overall increase in costs over 3 years due to higher costs of treatment. By the third year, savings in medical costs, primarily in chronic kidney disease costs, would offset most of the increase in treatment costs. Expanded use of febuxostat in the treatment of all gout patients, independent of renal impairment status, should be considered based on improved clinical outcomes and longer-term medical cost savings associated with these improved outcomes.

Febuxostat in the management of gout: a cost-effectiveness analysis.

OBJECTIVE: To determine the cost-effectiveness of febuxostat vs allopurinol for the management of gout. METHODS: A stochastic microsimulation cost-effectiveness model with a US private-payer perspective and 5-year time horizon was developed. Model flow based on guideline and real-world treatment paradigms incorporated gout flare, serum uric acid (sUA) testing, treatment titration, discontinuation, and adverse events, chronic kidney disease (CKD) incidence and progression, and type 2 diabetes mellitus (T2DM) incidence. Outcomes were estimated for the general gout population and for gout patients with CKD stages 3/4. Modeled treatment interventions were daily oral febuxostat 40-80 mg and allopurinol 100-300 mg. Baseline patient characteristics were taken from epidemiologic studies, efficacy data from randomized controlled trials, adverse event rates from package inserts, and costs from the literature, government sources, and expert opinion. Eight clinically-relevant incremental cost-effectiveness ratios were estimated: per patient reaching target sUA, per flare avoided, per CKD incidence, progression, stages 3/4 progression, and stage 5 progression avoided, per incident T2DM avoided, and per death avoided. RESULTS: Five-year incremental cost-effectiveness ratios for the general gout population were $5377 per patient reaching target sUA, $1773 per flare avoided, $221,795 per incident CKD avoided, $29,063 per CKD progression avoided, $36,018 per progression to CKD 3/4 avoided, $71,426 per progression to CKD 5 avoided, $214,277 per incident T2DM avoided, and $217,971 per death avoided. In patients with CKD 3/4, febuxostat dominated allopurinol for all cost-effectiveness outcome measures. CONCLUSIONS: Febuxostat may be a cost-effective alternative to allopurinol, especially for patients with CKD stages 3 or 4.

A Real-World Study of Switching From Allopurinol to Febuxostat in a Health Plan Database.

OBJECTIVE: The objective of this study was to assess the real-world comparative effectiveness of continuing on allopurinol versus switching to febuxostat. METHODS: In a retrospective claims data study of enrollees in health plans affiliated with Optum, we evaluated patients from February 1, 2009, to May 31, 2012, with a gout diagnosis, a pharmacy claim for allopurinol or febuxostat, and at least 1 serum uric acid (SUA) result available during the follow-up period. Univariate and multivariable-adjusted analyses (controlling for patient demographics and clinical factors) assessed the likelihood of SUA lowering and achievement of target SUA of less than 6.0 mg/dL or less than 5.0 mg/dL in allopurinol continuers versus febuxostat switchers. RESULTS: The final study population included 748 subjects who switched to febuxostat from allopurinol and 4795 continuing users of allopurinol. The most common doses of allopurinol were 300 mg/d or less in 95% of allopurinol continuers and 93% of febuxostat switchers (prior to switching); the most common dose of febuxostat was 40 mg/d, in 77% of febuxostat switchers (after switching). Compared with allopurinol continuers, febuxostat switchers had greater (1) mean preindex SUA, 8.0 mg/dL versus 6.6 mg/dL (P < 0.001); (2) likelihood of postindex SUA of less than 6.0 mg/dL, 62.2% versus 58.7% (P = 0.072); (3) likelihood of postindex SUA of less than 5.0 mg/dL, 38.9% versus 29.6% (P < 0.001); and (4) decrease in SUA, 1.8 (SD, 2.2) mg/dL versus 0.4 (SD, 1.7) mg/dL (P < 0.001). In multivariable-adjusted analyses, compared with allopurinol continuers, febuxostat switchers had significantly higher likelihood of achieving SUA of less than 6.0 mg/dL (40% higher) and SUA of less than 5.0 mg/dL (83% higher). CONCLUSIONS: In this "real-world" setting, many patients with gout not surprisingly were not treated with maximum permitted doses of allopurinol. Patients switched to febuxostat were more likely to achieve target SUA levels than those who continued on generally stable doses of allopurinol.