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Background Atypical antipsychotics are indicated for specific psychiatric conditions; however, they are frequently used for US Food and Drug Administration–nonapproved indications. Objective This study assessed the types of medical diagnoses associated with atypical antipsychotic prescriptions in commercial health care plans. Methods This retrospective cohort study used the OptumInsight commercial data set from January 2008 to June 2011. The index date was defined as the earliest date of prescription for the atypical antipsychotics aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone, from January 1, 2009, through June 30, 2010. Medical claims during a 2-year period (12 months before and 12 months after the index date) were used to identify relevant diagnostic codes from the International Classification of Diseases, Ninth Edition, Clinical Modification associated with the antipsychotic prescription. A logistic regression analysis was conducted to examine the predictors of use of atypical antipsychotics without a relevant diagnosis, that is, schizophrenia, bipolar, or major depressive disorder (MDD). Results Of 18,352 patients included in the analysis, 3593 (19.5%) who filled a prescription for atypical antipsychotics did not have an approved diagnosis. Off-label utilization varied, with approximately a quarter of patients with prescriptions for quetiapine (24.1%), risperidone (23.1%), or olanzapine (21.8%) being without a relevant diagnostic code, whereas proportions were lower for patients prescribed aripiprazole (14.0%) or ziprasidone (13.1%). Of those with a psychiatric disorder other than schizophrenia, bipolar disorder, or MDD, approximately a third of prescriptions were for anxiety disorders, with similar proportions across all atypical antipsychotics. Patients were often prescribed quetiapine for substance abuse (22.7%), whereas patients with "other psychiatric conditions" were prescribed risperidone (26.3%) or ziprasidone (25.0%). The logistic regression analysis indicated that patients prescribed olanzapine, quetiapine, or risperidone were significantly more likely to have no diagnostic code for schizophrenia, bipolar disorder, or MDD compared with patients prescribed aripiprazole. Conclusion Nearly a fifth of commercially insured patients were prescribed atypical antipsychotics, in particular, olanzapine, quetiapine, or risperidone, for diagnoses that were not aligned with US Food and Drug Administration–approved indications.

ObjectivesThis is the first study to compare the incidence and health care costs of medically attended adverse effects in atazanavir- and darunavir-based antiretroviral therapy (ART) among U.S. Medicaid patients receiving routine HIV care.MethodsThis was a retrospective study using Medicaid administrative health care claims from 15 states. Subjects were HIV patients aged 18 to 64 years initiating atazanavir- or darunavir-based ART from January 1, 2003, to July 1, 2010, with continuous enrollment for 6 months before (baseline) and 6 months after (evaluation period) ART initiation and 1 or more evaluation period medical claim. Outcomes were incidence and health care costs of the following medically attended (International Classification of Diseases, Ninth Revision, Clinical Modification–coded or treated) adverse effects during the evaluation period: gastrointestinal, lipid abnormalities, diabetes/hyperglycemia, rash, and jaundice. All-cause health care costs were also determined. Patients treated with atazanavir and darunavir were propensity score matched (ratio = 3:1) by using demographic and clinical covariates. Multivariable models adjusted for covariates lacking postmatch statistical balance.ResultsPropensity-matched study sample included 1848 atazanavir- and 616 darunavir-treated patients (mean age 41 years, 50% women, 69% black). Multivariable-adjusted hazard ratios (HRs) (for darunavir, reference = atazanavir) and per-patient-per-month health care cost differences (darunavir minus atazanavir) were as follows: gastrointestinal, HR = 1.25 (P = 0.04), $43 (P = 0.13); lipid abnormalities, HR = 1.38 (P = 0.07), $3 (P = 0.88); diabetes/hyperglycemia, HR = 0.84 (P = 0.55), $13 (P = 0.69); and rash, HR = 1.11 (P = 0.23), $0 (P = 0.76); all-cause health care costs were $1086 (P

In US treatment guidelines, efavirenz (EFV) is the preferred non-nucleoside reverse transcriptase inhibitor (NNRTI) for first-line HIV treatment. In the ECHO and THRIVE trials comparing EFV with another NNRTI, rilpivirine (RPV), both medications had similar virologic suppression rates at 96-weeks; however, RPV had higher rates of virologic failure and drug resistance and lower rates of discontinuation due to adverse events. This study compared the cost-effectiveness of EFV to RPV in first-line HIV treatment in the US.A Markov model with 14 health states was constructed to estimate 10-year costs and clinical outcomes from a US payer perspective for antiretroviral naïve HIV patients initiating EFV or RPV. First-line efficacy data came from 96-week results of the ECHO and THRIVE trials, which compared EFV and RPV, both in combination with two nucleos(t)ide reverse transcriptase inhibitors. Other clinical inputs, mortality rates, and costs (2011 US$) came from published sources. Subsequent therapy lines (second, third, non-suppressive) were based on US treatment guidelines and common to both treatment arms. Robustness of study results was assessed in sensitivity analyses varying model inputs by ±25%. Potential limitations of the model center on the ability of any model to capture the clinical complexity of HIV treatment.In the base case, 10-year costs were lower for EFV compared to RPV ($214,031 vs $222,090). Life expectancy (8.44 years) and years without AIDS (8.40 years) were equal; years in virologic suppression were similar (EFV = 7.87 years, RPV = 7.86 years). EFV had modest cost savings compared to RPV in terms of incremental cost-effectiveness per life-year gained, life-year gained in viral suppression, and life-year gained without AIDS. In sensitivity analyses, EFV remained cost-saving compared to RPV in over 90% of scenarios, demonstrating the robustness of study results.EFV was predicted to be modestly cost-saving compared with RPV over 10 years in US patients initiating first-line HIV treatment. Sensitivity analyses suggest that results may hold across multiple settings.

BackgroundTimely linkage to appropriate care after human immunodeficiency virus (HIV) diagnosis is critical to optimizing patient outcomes. Medicaid is the largest source of health care coverage for patients with HIV in the United States, yet no studies of linkage to appropriate HIV care have focuse

To compare pharmacotherapy adherence, persistence, and healthcare utilization/costs among US patients with chronic hepatitis B (CHB) initiated on an oral antiviral monotherapy recommended as first-line treatment by current national (US) guidelines vs an oral antiviral not recommended as first-line monotherapy.In this retrospective cohort study, patients aged 18-64 with medical claims for CHB who initiated an oral antiviral monotherapy for CHB between 07/01/05 and 01/31/10 were identified from a large US commercial health insurance claims database. Patients were continuously enrolled for a 6-month baseline period and ≥90 days follow-up. They were assigned to 'currently recommended first-line therapy' (RT: entecavir or tenofovir) or 'not currently recommended first-line therapy' (NRT: lamivudine, telbivudine, or adefovir) cohorts.Multivariate analyses were conducted to compare treatment adherence, persistence, healthcare utilization, and costs for RT vs NRT cohorts.Baseline characteristics were similar between RT (n=825) and NRT (n=916) cohorts. In multivariate analyses, RT patients were twice as likely as NRT patients to be adherent (OR=2.09; p0.01) and persistent (mean: RT=361 days, NRT=298 days; p0.01) and half as likely to have an inpatient stay (OR=0.527; p0.01). Between the two oral antivirals recommended as first-line treatment, even though pharmacy cost was higher for entecavir, mean total healthcare costs for entecavir and tenofovir were similar ($1214 and $1332 per patient per month, respectively). Similar results were also observed with regard to adherence, persistence, and healthcare use for entecavir and tenofovir.A limitation associated with analysis of administrative claims data is that coding errors can be mitigated but are typically not fully eradicated by careful study design. Nevertheless, the current findings clearly indicate the benefits of initiating CHB treatment with an oral antiviral monotherapy recommended as first-line treatment by current guidelines.

Background Despite the availability of effective treatments for depression, many patients under the care of primary care physicians do not achieve remission. Clinical Outcomes in Measurement-based Treatment (COMET) was designed to assess whether communicating patient-reported depression symptom severity to primary care physicians affects patient outcomes at 6 months. Methods Nine hundred fifteen patients (intervention: n = 503; control: n = 412) diagnosed with major depressive disorder were enrolled in a prospective trial in which physician practice sites were assigned to either the intervention or control study arm. Only patients who were prescribed an antidepressant by their physician were eligible, but medication type was independent of the study protocol. Intervention-arm physicians received monthly updates on their patients’ depression severity, which was determined with the nine-item Patient Health Questionnaire (PHQ-9) administered during telephone interviews. Remission was defined as a PHQ-9 score

To compare antiretroviral therapy (ART) adherence and persistence and total healthcare expenditures in Medicaid-insured patients with human immunodeficiency virus (HIV) initiating preferred or nonpreferred first-line ART based on March 2012 HHS HIV treatment guidelines.Retrospective observational study using Medicaid administrative healthcare claims from 15 states.Subjects were HIV patients 18 to 64 years who initiated first-line HIV-related ART between January 1, 2007, and September 30, 2011, with continuous enrollment for 6 months prior to and at least 3 months following ART initiation. Patients were classified as having initiated preferred or nonpreferred ART based on March 2012 HHS HIV treatment guidelines. Outcomes were: ART adherence (proportion of days covered dichotomized at ≥80% and ≥95%), time to ART nonpersistence, and per patient per month (PPPM) total healthcare expenditures. Outcomes were evaluated using multivariable regressions.Sample included 1979 patients initiating preferred ART regimens and 1614 patients initiating nonpreferred ART; overall mean age was 41 years; 48% of subjects were female. In the multivariable analyses, patients initiating preferred ART regimens had significantly greater odds of adherence ≥80% (odds ratio [OR], 1.38; 95% CI, 1.07-1.77) and adherence ≥95% (OR, 1.26; 95% CI, 1.05-1.51), and a significantly lower hazard of nonpersistence (HR, 0.48; 95% CI, 0.44-0.52). PPPM total healthcare expenditures were numerically lower for patients initiating preferred ART regimens (-$341; 95% CI, -$888 to $255) but the difference was not deemed significant.This study reinforces the value of HHS recommendations for first-line ART. The potential impact of these findings will grow as more HIV patients become Medicaid-eligible under the Patient Protection and Affordable Care Act.

Metabolic abnormalities observed with atypical antipsychotic treatment may be specific to each antipsychotic medication. The association between atypical antipsychotics and risk factors for cardiovascular disease prompted the American Diabetes Association (ADA) and the American Psychiatric Association (APA) to issue a consensus statement that categorized aripiprazole and ziprasidone as atypical antipsychotics with a lower likelihood of metabolic abnormalities.The aim of the current systematic review was to evaluate real-world studies (i.e. observational/naturalistic and open-label studies) assessing the risk for weight gain, dyslipidemia, glucose abnormalities, and diabetes mellitus in adult patients receiving treatment with atypical antipsychotics, with a specific focus on aripiprazole.A systematic PubMed search for articles published between 1 January 2000 and 4 October 2011 was performed using the following search terms in the title and abstract: aripiprazole, atypical, glucose, insulin, cholesterol, triglycerides, diabetes, hemoglobin A1c, weight, body mass index, and hyperlipidemia.Twenty-two peer-reviewed articles were found that assessed the metabolic effects associated with aripiprazole treatment, including studies from small observational trials to large databases (n = 15 to n 1,700,000). Thirteen articles reported observational or naturalistic studies, and nine were open-label trials evaluating weight gain, dyslipidemia, glucose abnormalities, and the risk of developing diabetes in adult patients receiving treatment with aripiprazole. Compared with other atypical antipsychotics, aripiprazole was either less likely to have an impact or had a comparable impact on weight gain and dyslipidemia; the degree of effect appeared to be dependent on study design. In addition, there was less risk of diabetes mellitus with aripiprazole compared with most other atypical antipsychotic agents.Consistent with data from randomized controlled studies, the current review of observational/naturalistic and open-label studies suggests aripiprazole may be associated with a lower risk than other commonly used atypical antipsychotics for metabolic adverse events in adults, consistent with the ADA/APA consensus statement.

To determine the comparative efficacy and tolerability of abatacept and tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA) and inadequate response to conventional disease modifying anti-rheumatic drugs (DMARDs). A systematic review identified RCTs in RA patients who responded inadequately to conventional DMARDs and were treated with one of the following biologic agents: abatacept, adalimumab, etanercept, infliximab, certolizumab pegol, or golimumab. Bayesian hierarchical models were used to compare efficacy and tolerability outcomes of abatacept and combined TNFi at 6 months and 1 year. In this mixed treatment comparison (MTC), the likelihood of achieving ACR response was comparable between abatacept and combined TNFi at 6 months for ACR20, 50, and 70: (odds ratio [OR] = 0.98 [95% confidence interval (CI): 0.73, 1.27], 0.99 [0.73, 1.31], and 0.91 [0.62, 1.27], respectively); and at 12 months for ACR20 (OR = 1.27 [0.92, 1.71]) and ACR50 (1.21 [0.82, 1.68]), with a higher likelihood of achieving an ACR70 response at 12 months (1.41 [1.02, 1.82]). Odds of DAS28 remission at 12 months was greater for abatacept than the combined TNFi (OR = 2.03 [1.04, 3.58]). Abatacept had better tolerability, defined as a lower likelihood of withdrawal due to adverse events, at both 6 and 12 months (OR = 0.38 [0.10, 0.88] and 0.51 [0.27, 0.86], respectively). These analyses include indirect comparisons across clinical trials and are not a replacement for head-to-head data. While all TNFi have been grouped into one class, there may be some differences between the individual TNFi that are not captured in our study. In this MTC, abatacept demonstrated similar efficacy at 6 months, a higher likelihood of achieving ACR70 response and DAS28 remission at 12 months and better tolerability relative to the combined TNFi in patients with RA who had an inadequate response to conventional DMARDs.

There is evidence that earlier initiation of HIV antiretroviral therapy (ART) is associated with better outcomes, including lower morbidity and mortality. Based on recent studies indicating that Medicaid enrollees are more likely to have suboptimal access to medical care, we hypothesized that HIV severity at time of ART initiation is worse for Medicaid patients than patients with other health care coverage. We conducted a US retrospective analysis of GE Centricity Outpatient Electronic Medical Records spanning 1 January 1997 through 30 September 2009. Subjects included all adult HIV patients initiating first-line ART who had CD4+ results within 90 days pre-initiation. HIV stage was defined using CD4 ranges:500 (n=520), 351-500 (n=379), 201-350 (n=580), or ≤200 (n=406) cells/mm(3), with lower CD4 count being indicative of increased disease severity. Payer type was defined as the patient's primary payer: Medicaid, Medicare, commercial insurance, self-pay or other/unknown. After controlling for demographic and clinical covariates, cumulative logit models assessed the effect of payer type on HIV stage at ART initiation. The study included 1885 subjects with the primary payer being Medicaid (n=218), Medicare (n=330), commercial insurance (n=538), self-pay (n=159) or other/unknown (n=640). Final logit models demonstrated that, compared to patients on Medicaid, the odds of initiating ART at a higher CD4 range were significantly greater for those commercially insured (odds ratio [OR]=1.53; P=0.005), self-paying (OR=1.56; P=0.023) and other/unknown (OR=1.79; P0.001) and similar for patients enrolled in Medicare (OR=1.11; P=0.521). Medicaid patients initiated ART at a more advanced stage of HIV than patients who were commercially insured, self-paying, or had other/unknown coverage. With HIV treatment guidelines now supporting ART initiation in patients with higher CD4 counts, these findings underscore the need for mitigating barriers, particularly in the Medicaid population, that may delay treatment initiation.

The aim of this study was to investigate the dosing patterns of adjunctive quetiapine or adjunctive aripiprazole in the treatment of major depressive disorder from 2006 to 2010, and to evaluate the impact of Food and Drug Administration (FDA) approval on these dosing patterns. Patients included in the study were adults diagnosed with major depressive disorder, and treated with adjunctive aripiprazole or quetiapine between the years 2006 and 2010. The average daily dose and dose distribution were calculated and assessed statistically over the same time period. The mean daily dose for patients treated with adjunctive aripiprazole decreased from 13.5 mg/day in 2006 to 6.9 mg/day in 2010, whereas the mean daily dose for patients treated with quetiapine increased from 129 mg/day in 2006 to 139 mg/day in 2007, decreasing to 123 mg/day in 2010. The proportion of patients receiving FDA-recommended doses increased significantly for aripiprazole (86.3% in 2006 to 94.5% in 2010; P0.001) and remained relatively stable for quetiapine (21.3% in 2006 to 24.0% in 2010; NS). The majority of patients treated with quetiapine received doses below those recommended by the FDA throughout the study period. Aripiprazole was mostly prescribed at therapeutic doses (pre-FDA and post-FDA approval), although the mean dose decreased significantly over time.

The objective of this study was to examine adherence and persistency in HIV patients initiating first-line combination antiretroviral therapy (cART) with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen.Using US health insurance records, the authors identified all persons aged ≥ 18 years with HIV, who began NNRTI-based cART between 1 January 2003 and 30 September 2009. They examined adherence using proportion of days covered (PDC), and non-persistency based on evidence of discontinuation, switching or augmentation. Differences in non-adherence (1 - PC) and non-persistency were compared over 12 months, between three treatment groups: i) efavirenz, emtricitabine and tenofovir as a fixed-dose combination ('EFV/FTC/TDF'); ii) EFV-based regimens other than EFV/TDF/FTC, with ≥ 2 NRTIs ('EFV + ≥ 2 NRTIs'); and iii) nevirapine-based regimens with ≥ 2 NRTIs (NVP + ≥ 2 NRTIs).There were 1874 patients receiving EFV/FTC/TDF, 893 receiving EFV + ≥ 2 NRTIs and 207 receiving NVP + ≥ 2 NRTIs. Adherence was lower for both EFV + ≥ 2 NRTIs and NVP + ≥ 2 NRTIs than for EFV/FTC/TDF (rate ratio (RR) = 1.57 and 2.01, respectively; both p0.01), while non-persistency was higher (hazard ratio (HR) = 1.56, p0.01 and 1.70, p0.01, respectively).Adherence and persistency may differ between NNRTI-based regimens; additional analyses are needed to understand the reasons for these differences.

Naoky Tsai,1 Lennox Jeffers,2 Lael Cragin,3 Sonja Sorensen,3 Wenqing Su,3 Lisa Rosenblatt,4 Hong Tang,4 Tony Hebden,4 Timothy Juday41John A Burns School of Medicine, University of Hawaii, Honolulu, HI, USA; 2University of Miami School of Medicine, Miami, FL, USA; 3United BioSource Corporation, Bethesda, MD, USA; 4Bristol-Myers Squibb Company, Plainsboro, NJ, USABackground: Decompensated cirrhosis is a serious clinical complication of chronic hepatitis B (CHB) that places a large economic burden on the US health care system. Although entecavir has been shown to improve health outcomes in a cost-effective manner in mixed populations of CHB patients, the cost-effectiveness of entecavir has not been evaluated in CHB patients with decompensated cirrhosis.Methods: This study assessed the cost-effectiveness of entecavir versus adefovir, from a US payer perspective, in CHB patients with decompensated cirrhosis, using a health-state transition Markov model with four health states: hepatocellular carcinoma (HCC), HCC-free survival, post-liver transplant, and death. The model considered a hypothetical patient population similar to that included in a randomized controlled trial in the target population (ETV-048): predominantly male (74%), Asian (54%), mean age 52 years, hepatic decompensation (Child–Pugh score ≥ seven), hepatitis B e antigen-positive or -negative, treatment-naïve or lamivudine-experienced, and no liver transplant history. Clinical inputs were based on cumulative safety results for ETV-048 and published literature. Costs were obtained from published literature. Costs and outcomes were discounted at 3% per annum.Results: For 1000 patients over a 3-year time horizon, predicted overall survival and HCC-free survival were longer with entecavir than with adefovir (2.35 versus 2.30 years and 2.11 versus 2.03 years, respectively). Predicted total health care costs were $889 lower with entecavir than with adefovir ($91,878 versus $92,768). For incremental cost/life-year gained and incremental cost/HCC-free-year gained, entecavir was less costly and more effective than adefovir. Sensitivity analyses found the results to be robust to plausible variations in health-state costs and discount rate.Conclusion: This analysis suggests that entecavir improves survival outcomes in a cost-saving manner compared with adefovir in CHB patients with hepatic decompensation.Keywords: hepatocellular carcinoma, antiviral, survival, health economics, incremental net benefit

Background Use of atypical antipsychotics (AA) in combination with an antidepressant is recommended as an augmentation strategy for patients with depression. However, there is a paucity of data comparing aripiprazole and other AAs in terms of patient reported outcomes. Therefore, the objective of this study was to examine the levels of HRQoL and health utility scores in patients with depression using aripiprazole compared with patients using olanzapine, quetiapine, risperidone and ziprasidone. Methods Data were obtained from the 2009, 2010, and 2011 National Health and Wellness Survey (NHWS), a cross-sectional, internet-based survey that is representative of the adult US population. Only those patients who reported being diagnosed with depression and taking an antidepressant and an atypical antipsychotic for depression were included. Patients taking an atypical antipsychotic for less than 2 months or who reported being diagnosed with bipolar disorder or schizophrenia were excluded. Patients taking aripiprazole were compared with patients taking other atypical antipsychotics. Health-related quality of life (HRQoL) and health utilities were assessed using the Short Form 12-item (SF-12) health survey. Differences between groups were analyzed using General Linear Models (GLM) controlling for demographic and health characteristics. Results Overall sample size was 426 with 59.9% taking aripiprazole (n = 255) and 40.1% (n = 171) taking another atypical antipsychotic (olanzapine (n = 19), quetiapine (n = 127), risperidone (n = 14) or ziprasidone (n = 11)). Of the SF-12 domains, mean mental component summary (MCS) score (p = .018), bodily pain (p = .047), general health (p = .009) and emotional role limitations (p = .009) were found to be significantly higher in aripiprazole users indicating better HRQoL compared to other atypical antipsychotics. After controlling for demographic and health characteristics, patients taking aripiprazole reported significantly higher mean mental SF-12 component summary (34.10 vs. 31.43, p = .018), bodily pain (55.19 vs. 49.05, p = .047), general health (50.05 vs. 43.07, p = .009), emotional role limitations (49.44 vs. 41.83, p = .009), and SF-6D utility scores (0.59 vs. 0.56, p = .042). Conclusions Comparison of patients taking aripiprazole with a cohort of patients using another AA for depression demonstrated that aripiprazole was independently associated with better (both statistically and clinically) HRQoL and health utilities.

In this data snapshot, the IMS PharMetrics Database was examined to assess the prevalence of combination antipsychotic therapy for the years 2003 through 2009 among 122,349 commercially insured adult individuals with bipolar disorder, depression, or schizophrenia. Although all three diagnostic groups were associated with varying amounts of combination antipsychotic use that included aripiprazole, olanzapine, quetiapine, risperidone and ziprasidone, persons with schizophrenia exhibited the highest rates. These findings indicate that from the perspective of “practice-based evidence,” providers see value in combination therapy.

Many patients with depression do not respond to first-line antidepressant therapy and may require augmentation with another concurrent treatment such as a second antidepressant, a stimulant, a mood stabilizer, or a second-generation antipsychotic (SGA). The objective of this study was to examine the relationship between patient cost-sharing and the use of augmentation among a sample of commercially insured patients.Retrospective observational study of adult patients diagnosed with depression and receiving antidepressant therapy (n = 48,807).Logistic regression models estimated the likelihood of augmentation as a function of patient cost-sharing amounts. An alternative-specific conditional logit model of the likelihood of each augmentation class, varying the cost-sharing prices faced for each class, was also estimated. All models controlled for sociodemographic characteristics, physical and mental comorbidities, health plan type, and year of index antidepressant therapy initiation.The range of mean copayments paid by patients for augmentation therapy was from $27.05 (antidepressant) to $38.81 (SGA). A $10- higher cost-sharing index for all augmentation classes was associated with lower odds of augmentation (adjusted odds ratio = 0.85; 95% confidence interval 0.79-0.91). Doubling the costsharing amount for each augmentation class was associated with a smaller percentage of patients utilizing each class of augmentation therapy.Employers and payers should consider the relationship between cost-sharing and medication utilization patterns of patients with depression.

Despite the availability of effective treatments for depression, many patients under the care of primary care physicians do not achieve remission. Clinical Outcomes in Measurement-based Treatment (COMET) was designed to assess whether communicating patient-reported depression symptom severity to primary care physicians affects patient outcomes at 6 months.Nine hundred fifteen patients (intervention: n = 503; control: n = 412) diagnosed with major depressive disorder were enrolled in a prospective trial in which physician practice sites were assigned to either the intervention or control study arm. Only patients who were prescribed an antidepressant by their physician were eligible, but medication type was independent of the study protocol. Intervention-arm physicians received monthly updates on their patients' depression severity, which was determined with the nine-item Patient Health Questionnaire (PHQ-9) administered during telephone interviews. Remission was defined as a PHQ-9 score5 at 6 months; response was defined as a score reduction ≥50%.Among patients with baseline PHQ-9 score ≥5, 45.0% achieved remission (46.7% intervention versus 42.8% control) and 63.9% responded (67.0% intervention versus 59.7% control) at 6 months. After adjusting for baseline demographic and clinical variables, odds of remission (odds ratio [OR], 1.59 [95% CI, 1.07-2.37]) or response (OR, 2.02 [95% CI, 1.36-3.02]) were significantly greater for the intervention group than for control patients.This study demonstrated that regular patient symptom monitoring with feedback to physicians improved outcomes of depression treatment in the primary care setting. Determining reasons for the high observed nonremission rates requires further investigation.

To examine the effect of antipsychotic medication half-life on the risk of psychiatric hospital admission and emergency department (ED) visits among adults with schizophrenia.Retrospective claims-based cohort study of adult Medicaid patients with schizophrenia who were prescribed second-generation antipsychotic monotherapy following hospital discharge between 1/1/04 and 12/31/06. Cox proportional hazards models were applied to compare adjusted hazards of mental disorder admission among patients treated with oral antipsychotics that have either a long [risperidone (t(1/2) = 20 h), olanzapine (t(1/2) = 30 h), aripiprazole (t(1/2) = 75 h)] (n = 1479) or short [quetiapine (t(1/2) = 6 h), ziprasidone (t(1/2) = 7 h)] (n = 837) half-life. Day-level models controlled for baseline background characteristics and antipsychotic adherence over time as measured by gaps in the prescription record. Similar analyses examined either hospitalization or ED visits as separate endpoints.A significantly lower rate of hospitalization/ED visits was evident for long (0.74/patient-year) vs short (1.06/patient-year) half-life antipsychotics (p 0.001). The unadjusted rate of hospitalization alone was significantly lower for long (0.38/patient-year) vs short (0.52/patient-year) half-life antipsychotics (p = 0.005). Compared with short half-life antipsychotic drugs, the adjusted hazard ratio associated with long half-life medications was 0.77 (95% CI = 0.67-0.88) for combined hospitalization/ED visits and 0.80 (95% CI = 0.67-0.96) for hospitalization. The corresponding number needed to treat with long, rather than short, half-life medications to avoid one hospitalization was 16 patients for 1 year and to avoid one hospitalization or ED visit was 11 patients for 1 year.This study demonstrated an association between antipsychotic medication half-life and hospitalization, not a causal link. Patients using long half-life medications had fewer comorbid mental health conditions and took fewer psychiatric medications at baseline. Other unmeasured differences may have existed between groups and may partially account for the findings.In schizophrenia management, longer-acting second-generation antipsychotics were associated with a lower risk of hospital admission/ED visits for mental disorders.

To compare second-generation antipsychotics on time to and cost of psychiatric hospitalization in Medicaid beneficiaries with bipolar disorder.Retrospective study using healthcare claims from 10 US state Medicaid programs. Included beneficiaries were aged 18-64, initiated a single second-generation antipsychotic (aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone) between 1/1/2003-6/30/2008 (initiation date=index), and had a medical claim with an ICD-9-CM diagnosis code for bipolar disorder. A 360-day post-index period was used to measure time to and costs of psychiatric hospitalization (inpatient claims with a diagnosis code for a mental disorder [ICD-9-CM 290.xx-319.xx] in any position). Cox proportional hazards models and Generalized Linear Models compared time to and costs of psychiatric hospitalization, respectively, in beneficiaries initiating aripiprazole vs each other second-generation antipsychotic, adjusting for beneficiaries' baseline characteristics.Included beneficiary characteristics: mean age 36 years, 77% female, 80% Caucasian, aripiprazole (n=2553), mean time to psychiatric hospitalization or censoring=85 days; olanzapine (n=4702), 81 days; quetiapine (n=9327), 97 days; risperidone (n=4377), 85 days; ziprasidone (n=1520), 82 days. After adjusting for baseline characteristics, time to psychiatric hospitalization in beneficiaries initiating aripiprazole was longer compared to olanzapine (hazard ratio [HR]=1.52, p0.001), quetiapine (HR=1.40, p0.001), ziprasidone (HR=1.33, p=0.032), and risperidone, although the latter difference did not reach significance (HR=1.18, p=0.13). The adjusted costs of psychiatric hospitalization in beneficiaries initiating aripiprazole were significantly lower compared to those initiating quetiapine (incremental per-patient per-month difference=$42, 95% CI=$16-66, p0.05), but not significantly lower for the other comparisons.This study was based on a non-probability convenience sample of the Medicaid population. Analyses of administrative claims data are subject to coding and classification error.Medicaid beneficiaries with bipolar disorder initiating aripiprazole had significantly longer time to psychiatric hospitalization than those initiating olanzapine, quetiapine, or ziprasidone, and significantly lower adjusted costs for psychiatric hospitalization than those initiating quetiapine.

Objective To compare health care utilization and expenditures in patients with depression whose initial antidepressant (AD) treatment was augmented with a second-generation antipsychotic. Methods Claims data from January 1, 2001, through June 30, 2009, were used to select patients aged 18 to 64 years with depression treated with ADs augmented with aripiprazole, olanzapine, or quetiapine. Patients were required to have 6 months of continuous eligibility before the first AD prescription and 6 months after the second-generation antipsychotic augmentation (index) date. Utilization and expenditures were assessed for 6 months after the index date. Multivariate regression was used to estimate adjusted expenditures and risks for hospitalizations and emergency department visits. Results A total of 483 patients treated with aripiprazole, 978 with olanzapine, and 2471 with quetiapine were selected. Mean adjusted expenditures for aripiprazole were significantly lower than those for olanzapine for each service category (all-cause, all-cause medical care, mental health-related, and mental health-related medical care) and were significantly lower than those for quetiapine for each category with the exception of mental health-related. The adjusted risks for hospitalization and emergency department visits were significantly higher for quetiapine than for aripiprazole. Conclusions Compared with patients treated with ADs and aripiprazole, those treated with ADs and olanzapine or quetiapine had greater utilization and higher expenditures.

Previous studies have demonstrated an association between certain second-generation antipsychotics (SGAs) and diabetes mellitus. The study assessed the impact of SGA dose on hemoglobin A1C (HbA(1c) >6.0) levels in a real-world setting. Patients aged ≥ 18 years during 2002-2006 in Ingenix LabRx claims database were included. The database collects medical and prescription claims and a subset of laboratory results for an employed, commercially insured population distributed throughout the United States. Patients with previously diagnosed diabetes, identified by the ICD-9-CM code of 250.x or use of antidiabetic agents, were excluded. The main exposure measure was the cumulative dose over a 30 day period before the HbA(1c) test, calculated as [sum of (number of pills per day×strength)]/100. A logistic regression was used to examine the relation with HbA(1c) >6.0 by tertile of the cumulative dose and average daily dose, adjusted for the covariates. The study included 391 patients on olanzapine, 467 on quetiapine, and 262 on risperidone. Patients treated with aripiprazole or ziprasidone (n=212) were included as a secondary reference because of their minimal metabolic risk. Compared to lower (Tertiles 1 and 2) cumulative doses of risperidone, patients with a high cumulative dose of risperidone (Tertile 3) had a significantly higher odds ratio (OR) for HbA(1c) >6.0 (adjusted OR=2.45; 95% confidence interval=1.13-5.32; P=0.023). A similar increase in OR was seen in patients with high cumulative dose of olanzapine (2.41; 1.19-4.89; P=0.015). Analyses of average daily dose revealed that quetiapine ≥ 400 mg/day and risperidone ≥ 2 mg/day had an OR of 2.29 (1.04-5.06; P=0.041) and 2.28 (1.08-4.83; P=0.032), respectively, compared to aripiprazole/ziprasidone. Both olanzapine groups (≥ 10 and

Background In the absence of direct evidence from randomized clinical trials (RCTs), indirect evaluations such as mixed treatment comparisons use statistical techniques that allow for multiple comparisons to be made across therapies, thus providing clinicians and formulary committee members with information on comparative effectiveness. Objectives To compare the relative efficacy and tolerability of intravenous (IV) and subcutaneous (SC) abatacept with tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA) and an inadequate response to disease modifying anti-rheumatic drugs (DMARDs). Methods A systematic literature review (from 1990-June 2011) identified RCTs of IV and SC abatacept and TNFi (adalimumab, certolizumab, etanercept, golimumab, infliximab) in the DMARD inadequate responders. The five TNFi were combined into a single group for the current analyses and outcomes at 6 months were compared using Bayesian hierarchical models for mixed treatment comparison. Efficacy and safety outcomes of interest included ACR 20/50/70 responses, DAS28 remission and withdrawal due to adverse events (AEs) or due to any reason. Results Twenty publications describing 15 RCTs were identified. The likelihood of achieving ACR responses at 6 months was comparable between abatacept (both IV and SC) and TNFi: odds ratio [OR] for IV abatacept vs. TNFi for ACR 20 =0.97 [95% confidence interval (CI): 0.74, 1.25], ACR 50, 0.98 [0.73, 1.29], and ACR70, 0.99 [0.68, 1.35], and OR for SC abatacept vs. TNFi for ACR20 =1.05 [0.72, 1.49], ACR50, 1.09 [0.75, 1.51], and ACR70, 1.12 [0.71, 1.64]. The odds of achieving DAS28 remission compared to TNFi were also similar (1.22 [0.74, 1.89] and 1.19 [0.68, 1.95] for IV and SC, respectively). While the odds of withdrawals due to an AE were similar between IV and SC abatacept, the odds were significantly lower for SC abatacept compared to TNFi (0.79 [0.45-1.25] and 0.55 [0.26-0.94] for IV and SC, respectively). Both IV and SC abatacept had a similar likelihood as combined TNFi for withdrawal due to any reason (1.12 [0.61, 1.87] and 1.06 [0.49, 2.02], respectively). Conclusions After 6 months of therapy, both IV and SC abatacept had similar efficacy compared with TNFi in RA patients with an inadequate response to DMARDs. Compared with TNFi, withdrawal due to an AE were lower for both IV and SC abatacept, this reaching significance for the latter formulation. Disclosure of Interest M. Hochberg Consultant for: Bristol-Myers Squibb, Abbott Laboratories, Amgen, Genentech/Roche, and UCB Inc., S. Berry Consultant for: Bristol-Myers Squibb, K. Broglio Consultant for: Bristol-Myers Squibb, A. Nadkarni Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, L. Rosenblatt Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, D. Trivedi Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, T. Hebden Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb

Background Patients with rheumatoid arthritis (RA) often have significant comorbidity which, along with underlying RA severity, may impact both choice and response to treatment. We have previously shown that patients initiating first-line intravenous (IV) abatacept had higher baseline RA-related and overall health care costs and higher comorbidity scores than those patients initiating first line infliximab. However, it is not known how the characteristics of patients who switch to abatacept from a previous biologic compare with those prescribed other agents as a second-line biologic. Objectives To compare degree of comorbidity, disease (RA) severity, and baseline health care costs in RA patients prior to initiating second-line biologic treatment with abatacept, adalimumab, etanercept or infliximab. Methods Utilizing a large managed care plan claims database in the United States, an analysis was conducted in adult RA patients during the six months prior to initiating second-line biologic treatment with abatacept, adalimumab, etanercept or infliximab. The identification period was January 01, 2006 through June 15, 2010. Severity of overall comorbidity was described using Charlson Comorbidity Index (CCI) and all-cause health care costs, while RA-related health care costs (including medication costs) were used as a proxy measure of RA severity. Results A total of 10,330 RA patients were identified who initiated treatment with one of the study agents as second-line biologic therapy. Baseline CCI and total all-cause health care costs were significantly higher for abatacept-treated patients (p Conclusions As shown previously in first-line biologic patients, in a commercially insured population, patients initiating IV abatacept as second-line treatment demonstrated more baseline comorbidity than those who received adalimumab, etanercept, or infliximab, and greater severity of RA than those who received adalimumab or etanercept. Further research is required to better understand how pre-existing conditions and severity of RA impact selection of biologic therapy and subsequent response in this patient population. References Darkow, T et al. Comorbidity and Cost Burden of Patients Prior to Initiating Abatacept or Infliximab as First-Line Biologic Therapy for the Treatment of Rheumatoid Arthritis. Poster presentation, ACR Congress, November 5–9, 2011 Chicago, USA. Disclosure of Interest D. Trivedi Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, L. Rosenblatt Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, T. Darkow Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, B. Chastek Consultant for: Bristol-Myers Squibb, Employee of: OptumInsight, T. Hebden Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb

Background Several biologic agents are currently approved to treat adult patients with rheumatoid arthritis (RA). To date, no analyses have compared the cost-efficacy of biologics using data from a head-to-head trial. Objectives To compare the cost-efficacy of subcutaneous (SC) abatacept (ABA) vs. adalimumab (ADA) using efficacy endpoints from Year 1 of the AMPLE (Abatacept Versus Adalimumab Comparison in Biologic Naive RA Subjects with Background Methotrexate) trial, the first head-to-head trial of biologics in RA patients with an inadequate response to methotrexate (MTX). Methods AMPLE is a phase IIIb, non-inferiority trial, comparing the efficacy of ABA vs. ADA in adults with RA for ≤ 5 years diagnosed with moderate to high disease as defined by DAS28-CRP (≥ 3.2) at screening, despite treatment with MTX (at least 15 mg/wk). A cost-efficacy analysis determined the cost per patient achieving several clinical and patient-reported outcomes (PRO) over 1 year. Efficacy data including ACR responses (ACR20, ACR50, and ACR70), remission [DAS28 Results The cost-efficacy ratio between ABA and ADA for all ACR response rates was comparable (Only ACR50 responses shown in Table, in US Dollars and Euros). Other outcomes that were comparable at 1 year included: cost per remission [95% CI] (ABA: ($63,282, [$55,807-$73,265]); 39,649€ [34,965€-45,903€] ADA: $67,947 [$59,436-$79,083]); 47,098€ [41,198€-54,817€], cost per HAQ response (ABA: $45,366 [$41,643−$49,820]; 28,424€ [26,091€-31,214€] ADA: $49,947 [$45,625−$55,067]; 34,621€ [31,625-38,170€]), and cost per day gained without activity limitation ($323 [$287−$369]; 202€ [180€-231€] and $380 [$333−$442]; 263€[231€-307€] respectively). Conclusions The cost-efficacy of ABA versus ADA is comparable in adult RA patients, both in the United States and Europe, based on measures of clinical efficacy and patient-reported outcomes from the AMPLE trial. Disclosure of Interest D. Khanna Consultant for: Bristol-Myers Squibb, E. Massarotti Grant/research support from: Bristol-Myers Squibb, Consultant for: UCB, L. Rosenblatt Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, D. Budd Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, J. Sabater Employee of: Bristol-Myers Squibb, T. Hebden Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb

Background Patients (pts) with RA have an increased prevalence of cardiovascular disease (CVD). Whether due to disease-related factors or in part related to RA medications, many pts with RA have hyperlipidaemia, a risk factor for CVD. However, the prevalence of hyperlipidaemia in the RA population and the extent to which hyperlipidaemia impacts the risk of CVD in pts with RA has not been well characterised. Objectives To determine, using data from a real-world setting, the overall and sex-specific risk of CV events in pts with RA, with or without comorbid hyperlipidaemia, relative to those in a non-RA cohort. Methods This retrospective, cohort study using claims data from a US commercial health plan (2005–Q1 2011) included pts with ≥2 physician diagnoses of RA (ICD-9 714.0, 714.2) and a non-RA cohort, matched 3:1 with the RA cohort on demographics (age, gender, region, index year). Pts with only one RA diagnosis in the 12-month, pre-index (“baseline”) period were excluded. Follow up began at the index date, 1 year after initation of full coverage with medical and pharmacy benefits, and lasted until the first CV event, end of enrolment, or end of data availability. Incidence of the first hospitalised CV event (composite of myocardial infarction, ischaemic stroke, percutaneous coronary intervention /coronary artery bypass graft) in the post-index period was determined for each cohort and stratified by age, sex and the presence of hyperlipidaemia (defined by the presence of a ICD-9 272.xx diagnosis claim or antihyperlipidaemic agent drug claim during the pre-index period). Cox proportional-hazards regression determined the hazard ratio (HR) for CV events, using the presence of RA as the independent variable, controlling for other baseline covariates (age, sex, hyperlipidaemia, diabetes, hypertension). Results The RA cohort consisted of 51,130 pts and was matched with 154,292 non-RA pts (35.1% and 36.0% with hyperlipidaemia during baseline, respectively). The incidence of CV events per 1,000 person-years was 5.55 for the RA cohort and 3.56 for the non-RA cohort (crude risk ratio [RR]=1.56). Within the RA cohort, incidence was 8.28 for pts with hyperlipidaemia and 3.88 for pts without hyperlipidaemia (crude RR=2.13); in the non-RA cohort, incidence was 5.78 and 2.15 for those with and without hyperlipidaemia, respectively (crude RR=2.69). When controlling for covariates, the HR of CV events for pts with RA was 1.67 (95% CI: 1.50, 1.86) relative to non-RA pts. Among covariates, presence of hyperlipidaemia conferred a significant risk of CV events (p Conclusions This real-world analysis demonstrates that pts with RA have an increased risk of CV events and, as seen with the non-RA cohort, CV event rates are incrementally higher for those pts with hyperlipidaemia. Therefore, mitigating the increased CV risk associated with hyperlipidaemia and optimising lipid levels are key treatment strategies for pts with RA. Disclosure of Interest L. Rosenblatt Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, J. Curtis Grant/research support from: Roche/Genentech, UCB, Centocor, CORRONA, Amgen, Pfizer, Bristol-Myers Squibb, Crescendo, Abbott, Consultant for: Roche/Genentech, UCB, Centocor, CORRONA, Amgen, Pfizer, Bristol-Myers Squibb, Crescendo, Abbott, A. Yang Employee of: Bristol-Myers Squibb, T. Hebden Employee of: Bristol-Myers Squibb

Anagha Nadkarni,1 Iftekhar Kalsekar,1 Min You,1 Robert Forbes,2 Tony Hebden11Bristol-Myers Squibb, Plainsboro, NJ, USA; 2Otsuka Pharmaceutical Development and Commercialization, Princeton, NJ, USAObjective: To compare total medical costs and utilization over a 12-month period in commercially insured patients receiving FDA-approved adjunctive atypical antipsychotics (aripiprazole, olanzapine, or quetiapine) for depression.Methods: A retrospective claims analysis was conducted from 2005–2010 using the PharMetrics database. Subjects were adult commercial health-plan members with depression, identified using International Classification of Diseases codes and followed for 12 months after augmentation with an atypical antipsychotic. Outcomes included total medical costs, hospitalization, and ER visits. Generalized linear models and logistic regression were used to compare the total medical costs and the odds of hospitalization and ER visits between the treatment groups after adjusting for baseline demographic and clinical characteristics.Results: A total of 9675 patients with depression were included in the analysis, of which 68.4% were female, with a mean age of 45.2 (±12.0) years. Adjusted 12-month total medical costs were higher for olanzapine ($14,275) and quetiapine ($12,998) compared to aripiprazole ($9,801; P < 0.05 for all comparisons with aripiprazole). When divided into inpatient and outpatient costs, olanzapine and quetiapine had significantly higher adjusted inpatient costs compared to aripiprazole ($6,124 and $4,538 vs $2,976, respectively; P < 0.05 for all comparisons with aripiprazole). Similar results were seen for adjusted outpatient costs. Adjusted odds of hospitalization for olanzapine (odds ratio [OR] = 1.73; 95% CI confidence interval [CI] = 1.42–2.10) and quetiapine (OR = 1.40; 95% CI = 1.21–1.60) were significantly higher than aripiprazole at 12 months. The adjusted odds of an ER visit for olanzapine (OR = 1.40; 95% CI = 1.18–1.65) and quetiapine (OR = 1.62; 95% CI = 1.44–1.81) were also significantly higher compared to aripiprazole at 12 months.Conclusions: In commercially insured major depressive disorder patients, olanzapine and quetiapine were associated with higher total medical costs, the difference being primarily attributable to higher inpatient costs. Additionally, olanzapine and quetiapine were associated with significantly higher odds of hospitalization and ER visits compared to aripiprazole.Keywords: depression, atypical antipsychotics, adjunctive therapy

e17009 Background: Some studies have demonstrated the correlation between adherence and persistence to therapy and the effectiveness of that therapy, thereby reinforcing the need to optimize both as a core treatment strategy. Because available data are limited, we examined real world adherence and persistence to the 2nd generation tyrosine kinase inhibitors (TKIs) used to treat chronic myeloid leukemia (CML). Methods: An observational retrospective study was conducted using pooled Invision Data Mart and Pharmetrics claims data. Adult CML patients with at least two prescriptions for a 2nd generation TKI between July 1, 2006 and December 31, 2010 were identified and followed for a maximum of 6 months from their index date (first observed prescription date). Dasatinib and nilotinib patients with prior imatinib use in 6 month pre-index period were classified as second-line and those with no prior use as first-line patients. Adherence to treatment was defined by the medication possession ratio (MPR) and persistence as the proportion of patients refilling prescriptions within 1.5 times the days supply during the follow-up period. Results: Of the 276 CML patients identified, 179 received dasatinib (n=50 first-line; n=129 second-line) and 97 received nilotinib (n=27 first-line; n=70 second-line). Patient characteristics were similar across treatment groups. Proportions with MPR ≥85% were 64% and 75% for first- and second-line dasatinib and 48% and 61% for first- and second-line nilotinib. Persistence rates were 36% and 47% for first- and second-line dasatinib and 26% and 39% for first- and second-line nilotinib. Conclusions: In both first- and second-line use, dasatinib was associated with higher adherence and persistence than the corresponding nilotinib-treated group. The reason for the difference between these TKIs is not known and will require further study.