Comparison between guideline-preferred and nonpreferred first-line HIV antiretroviral therapy.

OBJECTIVES: 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. STUDY DESIGN: Retrospective observational study using Medicaid administrative healthcare claims from 15 states. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Depression monitoring and patient behavior in the Clinical Outcomes in MEasurement-Based Treatment (COMET) trial.

OBJECTIVE: In this secondary analysis of results of the Clinical Outcomes in MEasurement-Based Treatment (COMET) trial, patient behaviors that might account for the differences observed in clinical outcomes were examined. METHODS: Patients (N=914) diagnosed as having major depressive disorder participated in telephone interviews either monthly for six months (intervention) or at three and six months (usual care) asking about antidepressant medication-taking, use of psychotherapy or counseling, and participation in depression support groups. Physicians (N=83) in the intervention arm received monthly feedback regarding their patients' depression severity. RESULTS: A total of 664 (73%) patients completed the month 6 interview. The adjusted odds of current antidepressant use at six months were 85% greater (p=.01) for patients in the intervention (N=380) versus usual care (N=284) arms, according to multivariate regression analyses. CONCLUSIONS: More frequent measurement of depression symptoms was associated with greater medication persistence, which in turn may have mediated clinical improvements.

A review of real-world data on the effects of aripiprazole on weight and metabolic outcomes in adults.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Diagnoses associated with use of atypical antipsychotics in a commercial health plan: a claims database analysis.

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.

Mixed treatment comparison of efficacy and tolerability of biologic agents in patients with rheumatoid arthritis.

OBJECTIVE: 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). RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of health care payer type on HIV stage of illness at time of initiation of antiretroviral therapy in the USA.

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; P<0.001) 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.

Comparative incidence and health care costs of medically attended adverse effects among U.S. Medicaid HIV patients on atazanavir- or darunavir-based antiretroviral therapy.

OBJECTIVES: This 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. METHODS: This 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. RESULTS: Propensity-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<0.001). Too few instances of jaundice (11 in atazanavir and 1 in darunavir) occurred to support multivariable modeling. CONCLUSIONS: Medication tolerability can be critical to the success or failure of ART. Compared with darunavir-treated patients, atazanavir-treated patients had significantly fewer instances of medically attended gastrointestinal issues and more instances of jaundice and incurred significantly lower health care costs.

Cost-effectiveness of efavirenz vs rilpivirine in HIV patients initiating first-line combination antiretroviral therapy.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Medical costs and utilization in patients with depression treated with adjunctive atypical antipsychotic therapy.

OBJECTIVE: 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.

Dosing patterns of aripiprazole and quetiapine for adjunctive treatment of major depressive disorder (2006-2010).

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; P<0.001) 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.

Patterns and correlates of linkage to appropriate HIV care after HIV diagnosis in the US Medicaid population.

BACKGROUND: Timely 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 focused solely on the Medicaid population. METHODS: This is a retrospective study using Medicaid claims data from 15 states. Study sample comprised patients aged 18 to 64 years with 1 or more HIV tests between January 1, 2003, to May 1, 2010, followed or accompanied by HIV diagnosis. The "Test Index" corresponded to the HIV test that was temporally proximate to first HIV diagnosis. Study end point was linkage to appropriate HIV care, defined as receipt of CD4 and viral load tests as per US treatment guidelines. Time-to-event analyses characterized patterns and correlates of linkage to appropriate care. RESULTS: This study included 6684 patients, with a mean age of 35 years, 70% female, and 47% black race. Overall, 21.0% of patients linked to appropriate care within 1 year of the Test Index and 26.4% within 5 years. Compared with whites, blacks had a significantly shorter time to linkage to HIV appropriate care (hazard ratio, 2.034; P < 0.001). CONCLUSIONS: These findings in Medicaid patients newly diagnosed with HIV contrast with prior research show disparities in access to HIV care favoring whites. Overall, the proportion of patients who linked to appropriate HIV care was very low given the availability of effective treatment, suggesting a need for more effective interventions promoting timely linkage to appropriate care after diagnosis.

Adherence and persistence with non-nucleoside reverse transcriptase inhibitor-based antiretroviral regimens.

OBJECTIVE: 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. METHODS: 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). RESULTS: 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 p < 0.01), while non-persistency was higher (hazard ratio (HR) = 1.56, p < 0.01 and 1.70, p < 0.01, respectively). CONCLUSION: Adherence and persistency may differ between NNRTI-based regimens; additional analyses are needed to understand the reasons for these differences.

Cost-effectiveness of entecavir versus adefovir for the treatment of chronic hepatitis B in patients with decompensated cirrhosis from a third-party US payer perspective.

BACKGROUND: 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.

Adherence, persistence, healthcare utilization, and cost benefits of guideline-recommended hepatitis B pharmacotherapy.

OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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. MAIN OUTCOME MEASURES: Multivariate analyses were conducted to compare treatment adherence, persistence, healthcare utilization, and costs for RT vs NRT cohorts. RESULTS: 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; p<0.01) and persistent (mean: RT=361 days, NRT=298 days; p<0.01) and half as likely to have an inpatient stay (OR=0.527; p<0.01). 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. CONCLUSIONS: 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.

Comparison of health-related quality of life among patients using atypical antipsychotics for treatment of depression: results from the National Health and Wellness Survey.

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.

Clinical Outcomes in Measurement-based Treatment (Comet): a trial of depression monitoring and feedback to primary care physicians.

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 <5 at 6 months; response was defined as a score reduction ≥50%. RESULTS: 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. CONCLUSIONS: 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.

Trends in combination antipsychotic use among persons with commercial insurance: a data snapshot.

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.

Impact of cost-sharing on treatment augmentation in patients with depression.

OBJECTIVES: 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. STUDY DESIGN: Retrospective observational study of adult patients diagnosed with depression and receiving antidepressant therapy (n = 48,807). METHODS: 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. RESULTS: 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. CONCLUSIONS: Employers and payers should consider the relationship between cost-sharing and medication utilization patterns of patients with depression.

Effect of communicating depression severity on physician prescribing patterns: findings from the Clinical Outcomes in MEasurement-based Treatment (COMET) trial.

OBJECTIVE: In this secondary analysis from the Clinical Outcomes in MEasurement-based Treatment trial (COMET), we evaluated whether providing primary care physicians with patient-reported feedback regarding depression severity affected pharmacological treatment patterns. METHOD: Intervention-arm physicians received their patients' 9-item Patient Health Questionnaire scores monthly. Odds of having no change in antidepressant treatment during the 6-month study period were calculated. Relationships between depression symptom status (partial or nonresponse) at month 3 and treatment changes in months 3 through 6 were assessed. RESULTS: Among 503 intervention and 412 usual care (UC) patients with major depressive disorder, most received antidepressant monotherapy at baseline (79.4% UC vs. 88.4% intervention; P=.047). Few switched their baseline antidepressant (17.4%), increased their dose (12.4%) or augmented with a second medication (2%). Odds of having no change in antidepressant therapy did not differ significantly between study arms (odds ratio 1.21; 95% confidence interval 0.78-1.88; P=.392). Few month 3 partial or nonresponders had a regimen change over the following 3 months; the study arms did not differ significantly (partial responders: 4.1% UC vs. 7.7% intervention; P=.429; nonresponders: 14.6% UC vs. 15.9% intervention; P=.888). CONCLUSIONS: Among depressed patients treated in primary care, little active management was observed. The lack of treatment modification for the majority of partial and nonresponders was notable.

Medical care costs and hospitalization in patients with bipolar disorder treated with atypical antipsychotics.

BACKGROUND: A large proportion of costs associated with the treatment of bipolar disorder are attributable to patient hospitalization. OBJECTIVE: To investigate medical care costs and hospitalization rates among patients with bipolar disorder who were managed with aripiprazole compared with olanzapine, quetiapine, risperidone, or ziprasidone. METHODS: This retrospective cohort study assessed patients who were aged 18 to 64 years, diagnosed with bipolar disorder, and who were receiving therapy with aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone. This study was based on data from the PharMetrics claims database between January 1, 2003, and September 30, 2008. The study used a time-to-event framework. Cox proportional hazards models were used to assess the impact of each atypical antipsychotic on time to hospitalization, including all-cause and mental health-related reasons. Generalized linear models were used to compare costs per treated patient per month between the groups. Aripiprazole therapy was the reference group for all comparisons. RESULTS: Aripiprazole therapy showed a significantly lower hazard ratio (HR) for all-cause hospitalizations compared with olanzapine (HR, 1.4), quetiapine (HR, 1.4), risperidone (HR, 1.2), and ziprasidone (HR, 1.7); and for mental health-related hospitalizations compared with olanzapine, quetiapine, risperidone (HR, 1.3 each), and ziprasidone (HR, 1.7). Ziprasidone had higher unadjusted all-cause medical costs (US $1151 ± $2928) and unadjusted mental health-related costs (US $711 ± $2263) than the other antipsychotics that were included in this study, whereas aripiprazole had the lowest all-cause (US $804 ± $2523) and mental health-related costs (US $475 ± $2145) compared with the other antipsychotics. Quetiapine had the highest all-cause costs (US $1221; 95% confidence interval [CI], 1180-1263), and ziprasidone had the highest mental health-related costs (US $823; 95% CI, 754-898). Adjusted inpatient and emergency department all-cause costs were significantly lower for aripiprazole compared with all other atypical antipsychotics (P <.05), except olanzapine; however, the adjusted inpatient and emergency department mental health-related costs were significantly lower for aripiprazole only when compared with ziprasidone (P <.05). CONCLUSIONS: The costs of medical care for patients with bipolar disorder differ based on the type of medication used, which can affect the rate of hospitalization. Treatment with aripiprazole was associated with fewer hospitalizations, longer time to hospitalization, and therefore the lowest all-cause and mental health-related medical costs compared with olanzapine, quetiapine, risperidone, or ziprasidone. Therefore, aripiprazole may offer an economic advantage over other atypical antipsychotics in patients with bipolar disorder.