Prescription opioid utilization patterns, and associated outcomes, among privately insured patients prescribed opioids to manage pain associated with osteoarthritis.

OBJECTIVE: To describe utilization patterns, negative clinical outcomes and economic burden of patients diagnosed with osteoarthritis (OA) of the hip and/or knee who received a prescription for tramadol or non-tramadol opioids vs. non-opioid drugs. METHODS: Optum Healthcare Solutions, Inc. commercial claims data were used (1/2012--3/2017). Adults with ≥2 diagnoses of OA of the hip and/or knee, and ≥30 days supply of pain medications were identified during the three-year period from the date of first prescription (index date) after the first OA diagnosis. Drug utilization statistics in the follow-up period were summarized by initial treatment (i.e. tramadol, non-tramadol opioids, non-opioid drugs). Opioid initiators were matched to those initiated on non-opioid treatments using a propensity score model accounting for baseline characteristics. Matched pairs analysis compared outcomes for these cohorts. RESULTS: Of 62,715 total patients, 15,270 (24.3%) initiated treatment with opioids, including 3,513 (5.6%) on tramadol and 11,757 (18.7%) on non-tramadol opioids. Opioid initiators had more comorbidities, higher baseline healthcare costs, and were more likely to have OA of the hip. Among non-opioid initiators, 27.5% switched to tramadol and 63% switched to non-tramadol opioids. Among tramadol initiators, 71% switched to non-tramadol opioids. Patients initiated on opioids had 20.4% (p < .01) higher all-cause healthcare costs and higher percentages experiencing multiple negative clinical outcomes (all p < .01) compared to matched controls. CONCLUSIONS: Most patients with OA of the hip and/or knee either initiate on or switch to opioids for long-term management of OA-related pain despite known risks. This highlights the need for new treatments that delay or prevent use of opioids.

Oral anticoagulant underutilization among elderly patients with atrial fibrillation: insights from the United States Medicare database.

BACKGROUND: Oral anticoagulants (OACs) mitigate stroke risk in patients with atrial fibrillation (AF). The study aim was to analyze prevalence and predictors of OAC underutilization. METHODS: Newly diagnosed AF patients with a CHA2DS2-VASc score ≥ 2 were identified from the US CMS Database (January 1, 2013-December 31, 2017). Patients were stratified based on having an OAC prescription versus not and the OAC prescription group was stratified by direct OAC (DOACs) versus warfarin. Multivariable logistic regression models were used to examine predictors of OAC underutilization. RESULTS: Among 1,204,507 identified AF patients, 617,611 patients (51.3%) were not prescribed an OAC during follow-up (mean: 2.4 years), and 586,896 patients (48.7%) were prescribed an OAC during this period (DOAC: 388,629 [66.2%]; warfarin: 198,267 [33.8%]). Age ≥ 85 years (odds ratio [OR] 0.55, 95% confidence interval [CI] 0.55-0.56), female sex (OR 0.96, 95% CI 0.95-0.96), Black race (OR 0.78, 95% CI 0.77-0.79) and comorbidities such as gastrointestinal (GI; OR 0.43, 95% CI 0.41-0.44) and intracranial bleeding (OR 0.29, 95% CI 0.28-0.31) were associated with lower utilization of OACs. Furthermore, age ≥ 85 years (OR 0.92, 95% CI 0.91-0.94), Black race (OR 0.78, 95% CI 0.76-0.80), ischemic stroke (OR 0.77, 95% CI 0.75-0.80), GI bleeding (OR 0.73, 95% CI 0.68-0.77), and intracranial bleeding (OR 0.72, 95% CI 0.65-0.80) predicted lower use of DOACs versus warfarin. CONCLUSIONS: Although OAC therapy prescription is the standard of care for stroke prevention in AF patients, its overall utilization is still low among Medicare patients ≥ 65 years old, with specific patient characteristics that predict underutilization.

Effectiveness and Safety of Direct Oral Anticoagulants Among Patients with Non-valvular Atrial Fibrillation and Multimorbidity.

INTRODUCTION: In the USA, there is a steady rise of atrial fibrillation due to the aging population with increased morbidity. This study evaluated the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) among elderly patients with non-valvular atrial fibrillation (NVAF) and multimorbidity prescribed direct oral anticoagulants (DOACs). METHODS: Using the CMS Medicare database, a retrospective observational study of adult patients with NVAF and multimorbidity who initiated apixaban, dabigatran, or rivaroxaban from January 1, 2012 to December 31, 2017 was conducted. High multimorbidity was classified as having ≥ 6 comorbidities. Cox proportional hazard models were used to evaluate the hazard ratios of S/SE and MB among three 1:1 propensity score matched DOAC cohorts. All-cause healthcare costs were estimated using generalized linear models. RESULTS: Overall 36% of the NVAF study population had high multimorbidity, forming three propensity score matched (PSM) cohorts: 12,511 apixaban-dabigatran, 60,287 apixaban-rivaroxaban, and 12,567 dabigatran-rivaroxaban patients. Apixaban was associated with a lower risk of stroke/SE and MB when compared with dabigatran and rivaroxaban. Dabigatran had a lower risk of stroke/SE and a similar risk of MB when compared with rivaroxaban. Compared to rivaroxaban, apixaban patients incurred lower all-cause healthcare costs, and dabigatran patients incurred similar all-cause healthcare costs. Compared to dabigatran, apixaban patients incurred similar all-cause healthcare costs. CONCLUSION: Patients with NVAF and ≥ 6 comorbid conditions had significantly different risks for stroke/SE and MB when comparing DOACs to DOACs, and different healthcare expenses. This study's results may be useful for evaluating the risk-benefit ratio of DOAC use in patients with NVAF and multimorbidity.

Effectiveness and safety of apixaban vs warfarin among venous thromboembolism patients at high-risk of bleeding.

This study evaluated effectiveness and safety of apixaban versus warfarin among venous thromboembolism patients at high-risk of bleeding (defined as having at least one of the following bleeding risk factors: ≥75 years; used antiplatelet, NSAIDs, or corticosteroids; had prior gastrointestinal bleeding or gastrointestinal-related conditions; late stage chronic kidney disease). Adult venous thromboembolism patients initiating apixaban or warfarin with ≥1 bleeding risk factor were identified from Medicare and four commercial claims databases in the United States. To balance characteristics between apixaban and warfarin patients, stabilized inverse probability treatment weighting was conducted. Cox proportional hazards models were used to estimate the risk of recurrent venous thromboembolism, major bleeding, and clinically relevant non-major bleeding. In total, 88,281 patients were identified. After inverse probability treatment weighting, the baseline patient characteristics were well-balanced between the two cohorts. Among venous thromboembolism patients at high-risk of bleeding, apixaban was associated with significantly lower risk of recurrent venous thromboembolism, major bleeding and clinically relevant non-major bleeding. No significant interactions were observed between treatment and number of risk factors on major bleeding and clinically relevant non-major bleeding or between treatment and type of bleeding risk factors on any of the outcomes. In conclusion, apixaban was associated with significantly lower risk of recurrent venous thromboembolism and bleeding among venous thromboembolism patients at high-risk of bleeding. Effects were generally consistent across subgroups of patients with different number or type of bleeding risk factors.

All-Cause Health Care and Work Loss Burden Associated With Nonsteroidal Anti-Inflammatory Drug and Opioid Treatment in Employed Patients With Osteoarthritis.

INTRODUCTION: This study estimated all-cause health care resource utilization (HRU) and costs and work loss outcomes associated with pain management of employed patients with osteoarthritis of the hip and/or knee. METHODS: Optum Health Care Solutions data were analyzed for employed patients prescribed nonsteroidal anti-inflammatory drugs, tramadol, or nontramadol opioids following diagnoses of osteoarthritis of the hip and/or knee. A pre-post design was used to evaluate changes in all-cause HRU and costs, and work loss days and associated costs. RESULTS: Costs rose for patients in all three cohorts (up to 198.3% for health care costs [tramadol] and up to 178.7% for work loss costs [tramadol]). Greatest increases in all-cause HRU included inpatient visits (237.9% [nonsteroidal anti-inflammatory drugs]; 600% [tramadol]). CONCLUSIONS: Study results provide evidence of increases in all-cause HRU and costs and work loss days and associated costs.

A Retrospective Claims-Based Study Evaluating Clinical and Economic Burden Among Patients With Moderate to Severe Osteoarthritis Pain in the United States.

Background: There has been limited evaluation of medication adherence, healthcare resource utilization (HCRU), and healthcare costs over time in patients with osteoarthritis (OA), and stratification by pain severity level has not been reported. Assessing such longitudinal changes may be useful to patients and healthcare providers for tracking disease progression, informing treatment options, and employing strategies to optimize patient outcomes. Objectives: To characterize treatment patterns, HCRU, and costs over time in patients with moderate to severe (MTS) OA pain in the United States. Methods: We conducted a retrospective claims analysis, using IBM® MarketScan® databases, from 2013-2018. Eligible patients were aged ≥45 years with ≥12 months pre-index (baseline) and ≥24 months (follow-up) of continuous enrollment; index date was defined as a physician diagnosis of hip or knee OA. An algorithm was employed to identify MTS OA pain patients, who were propensity score matched with patients having non-MTS OA pain. Data were summarized using descriptive statistics and univariate analyses. Results: After propensity score matching, the overall OA pain cohorts consisted of 186 374 patients each: 61% were female, mean age was 63 years, and two-thirds (65.6%) were of working age (45-65 years). Sleep-related conditions, anxiety, and depression were significantly higher in the MTS OA pain cohort vs non-MTS (P<0.001). At baseline and 12- and 24-month follow-ups, receipt of prescription pain medications, HCRU, and direct medical costs were significantly higher in the MTS OA pain cohort (all P<0.01). Medication adherence was significantly higher in the MTS OA pain cohort for all medication classes except analgesics/antipyretics, which were significantly lower vs the non-MTS OA pain cohort (all P<0.0001). Conclusions: The burden of MTS OA pain is substantial, with patterns that show increasing medication use, HCRU, and costs vs non-MTS OA pain patients over time. Understanding the heterogeneity within the OA population may allow us to further appreciate the true burden of illness for patients in pain.

Drug utilization, clinical and economic outcomes of patients with osteoarthritis of the hip and/or knee treated with long-term use of traditional NSAIDs, topical NSAIDs, and COX-2 inhibitors.

OBJECTIVES: To describe and compare baseline characteristics, healthcare and drug utilization, and negative clinical outcomes of commercially-insured patients diagnosed with OA of the hip and/or knee who initiated treatment on traditional oral NSAIDs (tNSAIDs), topical NSAIDs, or cyclooxygenase-2 inhibitors (COX-2s). METHODS: A commercial claims database (1/2012-3/2017) was used to identify patients ≥18 years old, with ≥2 diagnoses of hip and/or knee OA, and ≥90 days supply of NSAIDs. Patients were assigned to cohorts based on the type of NSAID initially prescribed and observed in the 6 months before (baseline) and 36 months after (follow-up) the date of their first NSAID prescription after the first OA diagnosis. Analyses estimated baseline demographic and clinical characteristics and follow-up period drug utilization. Logistic regressions assessed the risk of gastrointestinal (GI) and acute renal failure (ARF) events. RESULTS: tNSAIDs were the most frequently prescribed treatment. During the follow-up period, less than 15% of patients prescribed tNSAIDs switched to either COX-2s or topical NSAIDs and 37% of patients prescribed a COX-2 and 56% of patients prescribed a topical NSAID switched to tNSAIDs. GI and ARF events during the follow-up period ranged from 7.3-8.1% and 8.0-11.0%, respectively, across cohorts. The tNSAIDs and COX-2s cohorts had increased risk of both types of events relative to patients prescribed topical NSAIDs, controlling for other characteristics. CONCLUSIONS: Analyses characterize the long-term real-world utilization of NSAIDs and associated outcomes for patients with OA of the hip and/or knee. Study results highlight the likelihood of switching and the risk of negative clinical outcomes associated with long-term use.

An Observational Retrospective Matched Cohort Study of Healthcare Resource Utilisation and Costs in UK Patients with Moderate to Severe Osteoarthritis Pain.

INTRODUCTION: Using data from patients residing in Salford, UK, we aimed to compare healthcare resource utilisation (HCRU) and direct healthcare costs between patients with moderate to severe (M-S) or severe osteoarthritis (OA) pain and those without OA. METHODS: Patients with a M-S OA pain event within a period of chronic pain were indexed from the Salford Integrated Record (SIR) between 2010 and 2017. Patients with a severe pain event formed an OA subcohort. Patients in each OA pain cohort were independently matched to patients without OA, forming two control cohorts. HCRU, prescribed analgesic drugs, and total direct costs per UK standardised tariffs were calculated for the year post-index. Multivariable models were used to identify drivers of healthcare cost. RESULTS: The M-S OA pain and control cohorts each comprised 3123 patients; the severe OA pain and control cohorts each comprised 1922 patients. Patients in both OA pain cohorts had a significantly higher mean number of general practitioner encounters, inpatient, outpatient, and accident and emergency visits, and were prescribed a broader range of analgesic drugs in the year post-index than respective controls. Mean healthcare costs of all types were significantly higher in the M-S and severe OA pain cohorts vs controls (total: M-S £2519 vs £1379; severe £3389 vs £1397). Paracetamol (M-S: 40% of patients had at least one prescription; severe: 50%) and strong opioids (34% and 59%) were the analgesics most prescribed to patients with OA pain. In all cohorts, multivariable models showed that a higher age at index, the presence of gout, osteoporosis, type 2 diabetes, or coronary artery disease, significantly contributed towards higher healthcare costs. CONCLUSION: In the population of Salford, UK, patients with M-S OA pain had significantly higher annual HCRU and costs compared with matched controls without OA; generally, these were even higher in patients with severe OA pain.

Contemporary clinical and economic outcomes among oral anticoagulant treated and untreated elderly patients with atrial fibrillation: Insights from the United States Medicare database.

BACKGROUND: Oral anticoagulants (OACs) mitigate the risk of stroke in atrial fibrillation (AF) patients. OBJECTIVE: Elderly AF patients who were treated with OACs (apixaban, dabigatran, edoxaban, rivaroxaban, or warfarin) were compared against AF patients who were not treated with OACs with respect to their clinical and economic outcomes. METHODS: Newly diagnosed AF patients were identified between January 2013 and December 2017 in the Medicare database. Evidence of an OAC treatment claim on or after the first AF diagnosis was used to classify patients into treatment-defined cohorts, and these cohorts were further stratified based on the initial OAC prescribed. The risks of stroke/systemic embolism (SE), major bleeding (MB), and death were analyzed using inverse probability treatment weighted time-dependent Cox regression models, and costs were compared with marginal structural models. RESULTS: The two treatment groups were composed of 1,421,187 AF patients: OAC treated (N = 583,350, 41.0% [36.4% apixaban, 4.9% dabigatran, 0.1% edoxaban, 26.7% rivaroxaban, and 31.9% warfarin patients]) and untreated (N = 837,837, 59.0%). OAC-treated patients had a lower adjusted risk of stroke/SE compared to untreated patients (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.68-0.72). Additionally patients receiving OACs had a lower adjusted risk of death (HR: 0.56; 95% CI: 0.55-0.56) and a higher risk of MB (HR: 1.57; 95% CI: 1.54-1.59) and this trend was consistent across each OAC sub-group. The OAC-treated cohort had lower adjusted total healthcare costs per patient per month ($4,381 vs $7,172; p < .0001). CONCLUSION: For the OAC-treated cohort in this elderly US population, stroke/SE and all-cause death were lower, while risk of MB was higher. Among OAC treated patients, total healthcare costs were lower than those of the untreated cohort.

Non-persistence to Oral Anticoagulation Treatment in Patients with Non-valvular Atrial Fibrillation in the USA.

BACKGROUND: Studies have shown that patients with non-valvular atrial fibrillation (NVAF) who discontinue oral anticoagulants (OACs) are at higher risk of complications such as stroke. OBJECTIVE: This analysis compared the risk of non-persistence with OACs among patients with NVAF. METHODS: Adult patients with NVAF who initiated apixaban, dabigatran, rivaroxaban, or warfarin were identified using 01JAN2013-30JUN2019 data from Centers for Medicare and Medicaid Services and four US commercial claims databases. Non-persistence was defined as discontinuation (no evidence of index OAC use for ≥ 60 days from the last days' supply) or switch to another OAC. Kaplan-Meier curves were generated to illustrate time to non-persistence along with cumulative incidences of non-persistence. Baseline and time-varying covariates were evaluated, and adjusted Cox proportional hazards models were used to evaluate non-persistence risk. RESULTS: In total, 363,823 patients receiving apixaban, 57,121 receiving dabigatran, 282,831 receiving rivaroxaban, and 317,337 receiving warfarin were included. Of these, 47-72% discontinued/switched OAC therapy within an average 9-month follow-up. Apixaban was associated with a lower risk of non-persistence than were dabigatran (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.61-0.62), rivaroxaban (HR 0.76; 95% CI 0.75-0.76), and warfarin (HR 0.74; 95% CI 0.74-0.75). Dabigatran was associated with a higher risk of non-persistence than were warfarin (HR 1.21; 95% CI 1.19-1.22) and rivaroxaban (HR 1.23; 95% CI 1.22-1.25), and rivaroxaban was associated with a lower risk of non-persistence than was warfarin (HR 0.98; 95% CI 0.97-0.98). Clinical events (stroke/systemic embolism and major bleeding [MB]) during follow-up were predictors of non-persistence (stroke HR 1.57; 95% CI 1.53-1.61; MB HR 2.96; 95% CI 2.92-3.00). CONCLUSION: In over one million patients with NVAF, our results suggest differences in anticoagulation treatment persistence across OAC agents, even after accounting for clinical events after OAC initiation. It is important for clinicians and patients to take these differences into consideration, especially as non-persistence to OAC therapy is associated with thromboembolic complications.

A Retrospective Cohort Analysis of the Impact of Osteoarthritis on Disability Leave, Workers' Compensation Claims, and Healthcare Payments.

OBJECTIVES: Examine short-term disability (STD) and workers' compensation (WC) associated leave and wage replacements, and overall direct healthcare payments, among employees with osteoarthritis (OA) versus other chronically painful conditions; quantifying the impact of opioid use. METHODS: Analysis of employees with more than or equal to two STD or WC claims for OA or pre-specified chronically painful conditions (control) in the IBM MarketScan Research Databases (2014 to 2017). RESULTS: The OA cohort (n = 144,355) had an estimated +1.2 STD days, +$152 STD payments, and +$1410 healthcare payments relative to the control cohort (n = 392,639; P < 0.001). WC days/payments were similar. Differences were partially driven by an association between opioid use, increased STD days/payments, and healthcare payments observed in pooled cohorts (P < 0.001). CONCLUSIONS: OA is associated with high STD days/payments and healthcare payments. Opioid use significantly contributes to these and this should be considered when choosing treatment.

Finite Mixture Models, a Flexible Alternative to Standard Modeling Techniques for Extrapolated Mean Survival Times Needed for Cost-Effectiveness Analyses.

OBJECTIVES: To compare finite mixture models with common survival models with respect to how well they fit heterogenous data used to estimate mean survival times required for cost-effectiveness analysis. METHODS: Publicly available overall survival (OS) and progression-free survival (PFS) curves were digitized to produce nonproprietary data. Regression models based on the following distributions were fit to the data: Weibull, lognormal, log-logistic, generalized F, generalized gamma, Gompertz, mixture of 2 Weibulls, and mixture of 3 Weibulls. A second set of analyses was performed based on data in which patients who had not experienced an event by 30 months were censored. Model performance was compared based on the Akaike information criterion (AIC). RESULTS: For PFS, the 3-Weibull mixture (AIC = 479.94) and 2-Weibull mixture (AIC = 488.24) models outperformed other models by more than 40 points and produced the most accurate estimates of mean survival times. For OS, the AIC values for all models were similar (all within 4 points). The means for the mixture 3-Weibulls mixture model (17.60 months) and the 2-Weibull mixture model (17.59 months) were the closest to the Kaplan-Meier mean estimate of (17.58 months). The results and conclusions from the censored analysis of PFS were similar to the uncensored PFS analysis. On the basis of extrapolated mean OS, all models produced estimates within 10% of the Kaplan-Meier mean survival time. CONCLUSIONS: Finite mixture models offer a flexible modeling approach that has benefits over standard parametric models when analyzing heterogenous data for estimating survival times needed for cost-effectiveness analysis.

Effectiveness and Safety of Apixaban Versus Warfarin Among Older Patients with Venous Thromboembolism with Different Demographics and Socioeconomic Status.

INTRODUCTION: Impact of demographics and socioeconomic status (SES) on anticoagulant treatment outcomes among patients with venous thromboembolism (VTE) is not well understood. This study evaluated risks of recurrent VTE, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) among older patients with VTE initiating apixaban or warfarin stratified by demographics and SES. METHODS: Adult patients (≥ 65 years) who initiated apixaban or warfarin after a VTE event were selected from the US CMS Medicare database (September 2014-December 2017). Stabilized inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. Patients were stratified by age, gender, race, and SES. For each subgroup, Cox proportional hazard models were used to evaluate if there was a significant interaction (p < 0.10) between treatment and subgroup for recurrent VTE, MB, and CRNMB. RESULTS: In total, 22,135 apixaban and 45,840 warfarin patients with VTE were included. Post-IPTW, patient characteristics were balanced between treatment cohorts. In older patients, apixaban treatment was associated with significantly lower risks of recurrent VTE (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.52-0.79), MB (HR 0.65; 95% CI 0.57-0.75), and CRNMB (HR 0.79; 95% CI 0.75-0.85) versus warfarin. When stratified by demographics and SES, higher incidence rates of recurrent VTE, MB, and CRNMB were observed for black vs white patients and patients with lower vs higher SES. Comparison of apixaban with warfarin by different demographic and SES subgroups showed generally consistent results as the overall analysis. For most subgroups, no significant interaction was observed between treatment and subgroup strata for recurrent VTE, MB, and CRNMB. CONCLUSION: Among older patients with VTE initiating apixaban or warfarin, higher rates of recurrent VTE and bleeding were observed in black patients and patients with lower SES. Apixaban had a lower risk of recurrent VTE, MB, and CRNMB compared to warfarin. Analyses of demographic and SES subgroups showed consistent findings.

Health outcomes and economic burden of hospitalized COVID-19 patients in the United States.

OBJECTIVE: The aims of this study were to evaluate health outcomes and the economic burden of hospitalized COVID-19 patients in the United States. METHODS: Hospitalized patients with a primary or secondary discharge diagnosis code for COVID-19 (ICD-10 code U07.1) from 1 April to 31 October 2020 were identified in the Premier Healthcare COVID-19 Database. Patient demographics, hospitalization characteristics, and concomitant medical conditions were assessed. Hospital length of stay (LOS), in-hospital mortality, hospital charges, and hospital costs were evaluated overall and stratified by age groups, insurance types, and 4 COVID-19 disease progression states based on intensive care unit (ICU) and invasive mechanical ventilation (IMV) usage. RESULTS: Of the 173,942 hospitalized COVID-19 patients, the median age was 63 years, 51.0% were male, and 48.5% were covered by Medicare. The most prevalent concomitant medical conditions were cardiovascular disease (73.5%), hypertension (64.8%), diabetes (40.7%), obesity (27.0%), and chronic kidney disease (24.2%). Approximately one-fifth (21.9%) of the hospitalized COVID-19 patients were admitted to the ICU and 16.9% received IMV; most patients (73.6%) did not require ICU admission or IMV, and 12.4% required both. The median hospital LOS was 5 days, in-hospital mortality was 13.6%, median hospital charges were $43,986, and median hospital costs were $12,046. Hospital LOS and in-hospital mortality increased with ICU and/or IMV usage and age; hospital charges and costs increased with ICU and/or IMV usage. Patients with both ICU and IMV usage had the longest median hospital LOS (15 days), highest in-hospital mortality (53.8%), and highest hospital charges ($198,394) and hospital costs ($54,402). LIMITATIONS: This retrospective administrative database analysis relied on coding accuracy and a subset of admissions with validated/reconciled hospital costs. CONCLUSIONS: This study summarizes the severe health outcomes and substantial hospital costs of hospitalized COVID-19 patients in the US. The findings support the urgent need for rapid implementation of effective interventions, including safe and efficacious vaccines.

Treatment patterns, unmet need, and impact on patient-reported outcomes of psoriatic arthritis in the United States and Europe.

Psoriatic arthritis (PsA) is a chronic, inflammatory disease. The effects of PsA real-world treatment patterns on patient-reported outcomes in the US and 5 European countries (EU5; France, Germany, Italy, Spain, UK) were evaluated. Respondents from the 2016 National Health and Wellness Survey received advanced therapies (e.g., biologic disease-modifying antirheumatic drugs [DMARDs]), other therapies, (e.g., conventional synthetic DMARDs), or no treatment. Assessments included demographics, disease severity (patient-reported), comorbidities (Charlson Comorbidity Index), health status (Short Form-36 Health Survey), depression (Patient Health Questionnaire-9), work productivity (Work Productivity and Activity Index), and treatment adherence (Morisky Medication Adherence Scale-8). Overall, 1037 respondents from the US and 947 respondents from the EU5 were included. Of these, 21.7% US and 7.3% EU5 respondents received advanced therapies; 16.6% and 28.5%, other therapies; and 61.7% and 64.2%, no treatment, respectively. During treatment with advanced or other therapies, 40.8-54.7% US and 57.7-58.9% EU5 respondents self-reported moderate or severe PsA. Respondents receiving advanced therapies had the highest Charlson Comorbidity Index score (US, 1.25; EU5, 1.42); the lowest scores were with no treatment (0.52 and 0.49, respectively). Employment was lowest with other therapies (US, 47.7%; EU5, 41.1%). Overall work impairment was reported by 57.9% US and 62.6% EU5 respondents receiving advanced therapies. Medication adherence was generally low in the US and medium in the EU5 (Morisky Medication Adherence Scale-8: low, US 40.1-46.7%, EU5, 29.0-35.2%; medium, US 29.3-36.1%, EU5 37.8-49.3%; high, US 23.8-24.0%; EU5, 21.7-27.0%). Advanced and other therapies reduced PsA severity; however, > 40% of respondents reported moderate or severe PsA during treatment. Better management and adherence may reduce unmet need and disease burden. Further work is required to improve PsA diagnosis and time to treatment initiation.

Healthcare Costs of Smokers Using Varenicline Versus Nicotine-Replacement Therapy Patch in the United States: Evidence from Real-World Practice.

INTRODUCTION: Varenicline (VAR) is an effective smoking-cessation therapy compared to the commonly used nicotine-replacement therapy patch (NRT-P). However, comparative real-world evidence on smoking-cessation therapies is limited, especially for economic outcomes. METHODS: Using national claims databases (2012-2016) in the United States (US), adults initiating VAR or NRT-P without use of any other smoking-cessation products were followed for up to 1 year on a quarterly basis. Outcomes included smoking-attributable (SA) (cardiovascular, diabetes, pulmonary diseases, and smoking cessation) and all-cause costs (2017 US dollars). Adjusted mean costs were estimated from multivariable regressions, with baseline characteristics and propensity scores as covariates. Annual adjusted costs were calculated from quarterly averages. RESULTS: The VAR cohort (n = 209,284) was younger (mean age 46.7 vs. 49.0 years) and had fewer comorbidities [mean Charlson Comorbidity Index (CCI): 0.8 vs. 1.6] than the NRT-P cohort (n = 34,593). After adjustment, VAR cohort had lower SA and all-cause medical costs than NRT-P cohort in Quarters 1-4 (Q1-Q4) of follow-up, and had lower SA and all-cause total costs in Q2-Q4. Annually, VAR cohort had higher SA total costs ($307) and lower all-cause costs (- $2089) than NRT-P cohort. Annual medical costs were lower in VAR cohort (- $640 for SA and - $2876 for all-cause), and pharmacy costs were higher ($762 for SA and $777 for all-cause). In adherent patients (VAR: n = 38,744; NRT-P: n = 2702), VAR patients had lower annual medical costs (- $794 for SA and - $1636 for all-cause) and higher pharmacy costs ($1175 for SA and $1269 for all-cause); differences in SA and all-cause total costs were not statistically significant between treatment groups. CONCLUSIONS: Lower SA and all-cause medical costs associated with the use of VAR versus NRT-P resulted in savings in all-cause total costs and, among adherent patients, potentially offset the high pharmacy costs of VAR. FUNDING: Pfizer, Inc.

Smoking Cessation Is Associated With Lower Indirect Costs.

OBJECTIVE: This study quantified differences in indirect costs due to decreased work productivity between current and former smokers. Former smokers were further categorized by number of years since quitting to assess corresponding differences. METHODS: Data on employed individuals were obtained from the 2013 US National Health and Wellness Survey (NHWS; N = 75,000). Indirect costs were calculated for current smokers and former smokers from weekly wages based on age and sex. RESULTS: The annual total indirect costs for current smokers were $1327.53, $1560.18, and $1839.87 higher than for those who quit 0 to 4 years, 5 to 10 years, and more than or equal to 11 years prior, respectively. There were no significant differences in mean total indirect costs between the former smoker groups. CONCLUSIONS: Current smokers showed significantly higher total annual indirect costs compared with former smokers, independently of the number of years since quitting smoking.

Burden of illness in fibromyalgia patients with comorbid depression.

OBJECTIVES: To assess the burden of fibromyalgia (FM) in patients with FM taking antidepressant medication for comorbid depression. METHODS: Symptom burden, impact on work and activity, and healthcare resource utilisation (HCRU) was examined at randomisation in patients enrolled in a clinical trial. Symptom burden was estimated based on self-reported health status measures. The Work Productivity and Activity Impairment: Specific Health Problem scale adapted to FM and a separate HCRU questionnaire were completed. The relationship between FM severity and burden was evaluated. RESULTS: The total population analysed comprised 193 patients; 71 (36.8%) had moderate FM and 119 (61.7%) severe FM. Patients had moderate pain, severe impairment in functioning due to FM, sleep disruption, mild anxiety, and mild depression. In the 7 days preceding randomisation, an average of 58.0% overall work impairment was reported, with 15.2% of working hours missed and 54.0% productivity while at work. In the 3 months preceding randomisation, on average, 5.0 visits per patient were made to healthcare professionals. Physical treatments were used by 34.7% and supplements by 31.6% of patients. Prescription and non-prescription medications, as well as professional services providing help with activities of daily living (ADL) that are impacted by FM, were used by >75% of patients. In addition, 50.4 hours of unpaid help was provided for ADL assistance. Total out-of-pocket expenditures were US$307.1, €410.4, or C$211.3, depending on location. FM burden worsened with increasing FM severity. CONCLUSIONS: This study demonstrates the significant burden of FM in patients with comorbid depression treated with an antidepressant.

Simplifying Fibromyalgia Assessment: The VASFIQ Brief Symptom Scale.

OBJECTIVES: We tested the ability of the VASFIQ, a seven-item scale composed of Fibromyalgia Impact Questionnaire (FIQ) visual analog scales (VASs), to quantify fibromyalgia global disease severity and identify fibromyalgia patients with significant symptoms of fatigue, poor sleep, depression or anxiety. METHODS: Spearman rank correlations were used to compare global VASFIQ, FIQ and Patient Global Impression of Change (PGIC) scores and individual FIQ VAS scores with full-length, validated questionnaire scores for fatigue (Multidimensional Assessment of Fatigue-Global Fatigue Index [MAF-GFI]), poor sleep (Medical Outcomes Study Sleep Problems Index [SPI]) and depression and anxiety (Hospital Anxiety and Depression Scale [HADS]). Patient scores used in the analyses were derived from 2229 patients enrolled in three pregabalin fibromyalgia trials. Receiver operating characteristic analyses determined VASFIQ cutoff scores identifying patients with clinically significant symptom levels using full-length, validated symptom questionnaires to define cases. RESULTS: Global VASFIQ and FIQ scores correlated highly at baseline and study endpoints (ρ = 0.94 and 0.97, respectively; both p<0.0001). Change in global VASFIQ and FIQ scores correlated similarly to PGIC scores at study endpoints (ρ = 0.58 and 0.61, respectively; both p<0.0001). Individual FIQ VAS scores correlated with corresponding full-length symptom questionnaire scores at baseline and study endpoints (VASfatigue with MAF-GFI, ρ = 0.64 and 0.76; VASsleep with SPI, ρ = 0.50 and 0.67; VASdepression with HADS-D, ρ = 0.43 and 0.62; VASanxiety with HADS-A, ρ = 0.47 and 0.67, respectively; p <0.0001 for all). Patients with significant symptoms of fatigue were identified by VASfatigue >7.5, poor sleep by VASsleep >7.9, depression by VASdepression >5.8 and anxiety by VASanxiety >6.0. VASFIQ global scores ≥31.4 and ≥45.0 identified patients with moderate and severe global fibromyalgia symptoms, respectively. CONCLUSIONS: The VASFIQ scale accurately quantifies global fibromyalgia severity and identifies patients with significant symptoms of fatigue, poor sleep, depression or anxiety with brevity, enabling rapid patient assessment and informing treatment decisions in busy clinics.

Efficacy of donepezil on maintenance of activities of daily living in patients with moderate to severe Alzheimer's disease and the effect on caregiver burden.

OBJECTIVES: This study investigated the efficacy of donepezil treatment on activities of daily living (ADLs) and social functioning in patients with moderate to severe Alzheimer's disease (AD) and the possible benefits of this treatment on caregiving time and stress levels. DESIGN: Randomized, double-blind, placebo-controlled, multinational study. SETTING: Patients resided in the community or in assisted living facilities who did not require skilled 24-hour nursing care. PARTICIPANTS: Two hundred ninety patients with moderate to severe AD (baseline standardized Mini-Mental State Examination score of 5-17). INTERVENTION: Donepezil (5 mg/d for 4 weeks and 10 mg/d per clinician's judgment thereafter) or placebo for 24 weeks. MEASUREMENTS: ADLs were assessed using the Disability Assessment for Dementia (DAD), the modified instrumental activities of daily living (IADL) scale (IADL+), and the modified Physical Self Maintenance Scale (PSMS+). Caregiver time spent assisting patients with basic and instrumental ADLs was recorded as part of the IADL+ and PSMS+ scales. Patients' social behavior was evaluated through the use of a caregiver diary that captured observations of patients' motivation, interactions, and engagement. Caregivers were evaluated for their levels of caregiver stress with a modified, multiple-item Caregiver Stress Scale (CSS). For each outcome measure, the mean change from baseline at Week 24 using a last observation carried forward (LOCF) analysis was calculated. RESULTS: IADL+ and PSMS+ mean change from baseline scores for donepezil-treated patients showed a slower decline during the study than placebo-treated patients (Week 24 LOCF mean treatment differences: IADL+ = 6.83, P <.0001; PSMS+ = 1.32, P =.0015). Significant differences between the groups in favor of donepezil were observed on the DAD for instrumental and basic ADLs and on the three components required for the completion of each ADL: initiation, planning and organization, and effective performance. At baseline, caregivers of patients treated with donepezil (n = 141) did not differ significantly from caregivers of patients treated with placebo (n = 146) with respect to demographics or mean total scores on the CSS. At Week 24 LOCF, the overall distribution of caregiver ratings on each of the three caregiver diary items favored donepezil-treated patients over placebo-treated patients (P <.005). At Week 24 LOCF, mean change from baseline scores for CSS total and individual domain scores (all domains except caregiving competence, personal gain, and management of distress) were better for caregivers of donepezil-treated patients than for those of placebo-treated patients (CSS total, mean treatment difference = 1.82). Caregivers of donepezil-treated patients reported spending less time assisting with ADLs than caregivers of placebo-treated patients (mean difference = 52.4 min/d). CONCLUSION: Donepezil demonstrated a significantly slower decline than placebo in instrumental and basic ADLs in these patients with moderate to severe AD. The ADL benefits in AD patients treated with donepezil were associated with less caregiving time and lower levels of caregiver stress.