Cost-effectiveness of Cabotegravir Long-Acting for HIV Pre-exposure Prophylaxis in the United States.

OBJECTIVE: Cabotegravir long-acting (CAB-LA) administered every 2 months was approved in the USA as pre-exposure prophylaxis (PrEP) for individuals at risk of acquiring human immunodeficiency virus (HIV)-1 infection based on the HIV Prevention Trials Network (HPTN) 083 and HPTN 084 clinical trials, which demonstrated superior reduction in HIV-1 acquisition compared with daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in men who have sex with men (MSM), transgender women (TGW), and cisgender women. A decision-analytic model was developed to assess the lifetime cost-effectiveness of initiating CAB-LA versus generic oral FTC/TDF for HIV PrEP in the USA from a healthcare sector perspective. METHODS: PrEP-eligible adults entered the Markov model receiving CAB-LA or FTC/TDF and could continue initial PrEP, transition to a second PrEP option, or discontinue PrEP over time. Efficacy was taken from the HPTN 083 and HPTN 084 clinical trials. Individuals who acquired HIV-1 infection incurred lifetime HIV-related costs, could transmit HIV onwards, and could develop PrEP-related resistance mutations. Input parameter values were obtained from public and published sources. Model outcomes were discounted at 3%. RESULTS: The model estimated that the CAB-LA pathway prevented 4.5 more primary and secondary HIV-1 infections per 100 PrEP users than the oral PrEP pathway, which yielded 0.2 fewer quality-adjusted life-years (QALYs) lost per person. Additional per-person lifetime costs were $9476 (2022 US dollars), resulting in an incremental cost-effectiveness ratio of $46,843 per QALY gained. Results remained consistent in sensitivity and scenario analyses, including in underserved populations with low oral PrEP usage. CONCLUSIONS: Our analysis suggests that initiating CAB-LA for PrEP is cost-effective versus generic daily oral FTC/TDF for individuals at risk of acquiring HIV-1 infection.

Comparing Real-World Healthcare Costs Associated with Single-Tablet Regimens for HIV-1: The 2-Drug Regimen Dolutegravir/Lamivudine vs. Standard 3- or 4-Drug Regimens.

INTRODUCTION: Dolutegravir/lamivudine (DTG/3TC) is a 2-drug regimen for HIV-1 treatment with long-term efficacy and good tolerability comparable to 3- or 4-drug regimens. This study evaluated DTG/3TC cost versus other standard single-tablet regimens during its first year of approval. METHODS: This retrospective study analyzed US claims data from adults with HIV-1. Eligibility criteria included ≥ 1 dispensing of DTG/3TC, DTG/abacavir (ABC)/3TC, bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), elvitegravir (EVG)/cobicistat (COBI)/FTC/TAF, and darunavir (DRV)/COBI/FTC/TAF (index date was first dispensing) and ≥ 6 months of continuous eligibility before index date (baseline period). All-cause and HIV-related healthcare costs were evaluated during the observation period (index date until earliest of end of continuous eligibility or data availability). Adjusted cost differences and adjusted cost ratios were estimated using multivariable regression models controlling for differences in baseline characteristics between cohorts. RESULTS: Overall, 22,061 individuals with HIV-1 and dispensed treatment with DTG/3TC (n = 590), DTG/ABC/3TC (n = 4355), BIC/FTC/TAF (n = 9068), EVG/COBI/FTC/TAF (n = 7081), or DRV/COBI/FTC/TAF (n = 967) were included. Most claims data were from men (mean age ~ 46 years). Mean unadjusted all-cause total healthcare costs per patient per month were significantly lower for DTG/3TC versus BIC/FTC/TAF and DRV/COBI/FTC/TAF, and mean unadjusted HIV-related healthcare costs per patient per month were significantly lower for DTG/3TC versus DRV/COBI/FTC/TAF. Cost differences were primarily driven by significantly lower pharmacy costs for DTG/3TC versus other regimens (P < 0.001), while medical costs were similar across cohorts. Results were similar among treatment-naive and treatment-experienced individuals. After adjusting for baseline covariates, significant adjusted cost differences were generally consistent with unadjusted findings. Adjusted cost ratios generally favored DTG/3TC for all-cause healthcare and HIV-related costs, with all pharmacy cost ratios favoring DTG/3TC (P < 0.001). CONCLUSION: Dolutegravir/lamivudine had the lowest healthcare costs of BIC/FTC/TAF, EVG/COBI/FTC/TAF, and DRV/COBI/FTC/TAF, and the lowest pharmacy costs of all regimens, in unadjusted and adjusted analyses and by treatment experience, supporting the economic benefits of DTG/3TC as an initial or switch regimen for HIV-1.

Cost-effectiveness and budget impact of dolutegravir/lamivudine for treatment of human immunodeficiency virus (HIV-1) infection in the United States.

BACKGROUND: Dolutegravir(DTG)/lamivudine(3TC) is the first 2-drug regimen recommended as an initial treatment for people living with HIV (PLHIV). OBJECTIVE: To assess the cost-effectiveness and potential budget impact of DTG/3TC in the US healthcare setting. METHODS: A previously published hybrid decision-tree and Markov cohort state transition model was adapted to estimate the incremental costs and health outcome benefits over a patients' lifetime. DTG/3TC was compared with current standard of care in treatment naive and treatment experienced virologically suppressed PLHIV. Health states included in the model were based upon virologic response and CD4 cell count, with death as an absorbing state. Clinical data was informed by the Phase III GEMINI 1 and 2 clinical trials, a published network meta-analysis (NMA) in treatment-naive patients and the Phase III TANGO clinical trial in treatment experienced patients. Costs and utilities were informed by published data and discounted annually at a rate of 3%. A separate 5-year budget impact analysis was conducted assuming 5%-15% uptake in eligible treatment naive and 10%-30% uptake in eligible treatment experienced patients. RESULTS: In the treatment naive analyses based on GEMINI 1 and 2, DTG/3TC dominated, i.e., was less costly and more effective, than all comparators. DTG/3TC resulted in 0.083 incremental quality-adjusted life-years (QALYs) at a cost saving of $199,166 compared with the DTG + tenofovir disoproxil(TDF)/emtricitabine(FTC) comparator arm. The incremental QALY and cost savings for DTG/3TC compared with DTG/abacavir(ABC)/3TC, cobicistat-boosted darunavir(DRV/c)/tenofovir alafenamide(TAF)/FTC, and bictegravir (BIC)/TAF/FTC, based on NMA results were 0.465, 0.142, and 0.698, and $42,948, $122,846, and $44,962, respectively. In the analyses of treatment-experienced virologically suppressed patients based on TANGO, DTG/3TC offered slightly lower QALYs (-0.037) with an estimated savings of $78,730 when compared with continuation of TAF-based regimen (TBR). Sensitivity analyses demonstrated that these conclusions were relatively insensitive to alternative parameter estimates. The budget impact analysis estimated that by 5th year a total of 70,240 treatment naive patients and 1,340,480 treatment experienced patients could be eligible to be prescribed DTG/3TC. The estimated budget savings over 5 years ranged from $1.12b to $3.35b (corresponding to 27,512 to 82,536 on DTG/3TC by year 5) in the lowest and highest uptake scenarios, respectively. CONCLUSION: In conclusion, DTG/3TC with its comparable efficacy and lower drug acquisition costs, has the potential to offer significant cost savings to US healthcare payers for the initial treatment of treatment naive patients and as a treatment switching option for virologically suppressed patients. DISCLOSURES: This study was funded in full by ViiV healthcare, Brentford, UK. Medical writing to support this study was also funded in full by ViiV Healthcare, Brentford, UK. Butler, Hayward, and Jacob are employees of HEOR Ltd, the company performing this study funded by ViiV Healthcare. Anderson is an employee of GlaxoSmithKline and owns shares in the company. Punekar, Evitt, and Oglesby are employees of ViiV Healthcare and own stocks in GlaxoSmithKline.

Estimating HIV Management and Comorbidity Costs Among Aging HIV Patients in the United States: A Systematic Review.

BACKGROUND: As life expectancy of patients infected with human immunodeficiency virus (HIV) approaches that of the general population, the composition of HIV management costs is likely to change. OBJECTIVES: To (a) review treatment and disease management costs in HIV, including costs of adverse events (AEs) related to antiretroviral therapy (ART) and long-term toxicities, and (b) explore the evolving cost drivers. METHODS: A targeted literature review between January 2012 and November 2017 was conducted using PubMed and major conferences. Articles reporting U.S. costs of HIV management, acquired immunodeficiency syndrome (AIDS)-defining events, end of life care, and ART-associated comorbidities such as cardiovascular disease (CVD), chronic kidney disease (CKD), and osteoporosis were included. All costs were inflated to 2017 U.S. dollars. A Markov model-based analysis was conducted to estimate the effect of increased life expectancy on costs associated with HIV treatment and management. RESULTS: 22 studies describing HIV costs in the United States were identified, comprising 16 cost-effectiveness analysis studies, 5 retrospective analyses of health care utilization, and 1 cost analysis in a resource-limited setting. Management costs per patient per month, including routine care costs (on/off ART), non-HIV medication, opportunistic infection prophylaxis, inpatient utilization, outpatient utilization, and emergency department utilization were reported as CD4+ cell-based health state costs ranging from $1,192 for patients with CD4 > 500 cells/mm3 to $2,873 for patients with CD4 < 50 cells/mm3. Event costs for AEs ranged from $0 for headache, pain, vomiting, and lipodystrophy to $31,545 for myocardial infarction. The mean monthly per-patient costs for CVD management, CKD management, and osteoporosis were $5,898, $6,108, and $4,365, respectively. Improvements in life expectancy, approaching that of the general population in 2018, are projected to increase ART-related and AE costs by 35.4% and comorbidity costs by 175.8% compared with estimated costs with HIV life expectancy observed in 1996. CONCLUSIONS: This study identified and summarized holistic cost estimates appropriate for use within U.S. HIV cost-effectiveness analyses and demonstrates an increasing contribution of comorbidity outcomes, primarily associated with aging in addition to long-term treatment with ART, not typically evaluated in contemporary HIV cost-effectiveness analyses. DISCLOSURES: This analysis was sponsored by ViiV Healthcare, which had no role in the analyses and interpretation of study results. Ward, Sugrue, Hayward, and McEwan are employees of HEOR Ltd, which received funding from ViiV Healthcare to conduct this study. Anderson is an employee of GlaxoSmithKline and holds shares in the company. Punekar and Oglesby are employees of ViiV Healthcare and hold shares in GlaxoSmithKline. Lopes was employed by ViiV Healthcare at the time of the study and holds shares in GlaxoSmithKline.

Retrospective analysis of comorbidities and treatment burden among patients with HIV infection in a US Medicaid population.

Objective: Comorbidities and comedications are important factors influencing optimal therapy because people are living longer with HIV infection. This study describes the long-term comorbidity profile and treatment burden among people with HIV-1 infection.Methods: This retrospective study included Medicaid claims data from patients with ≥1 antiretroviral (ARV) claim between 2016 and 2017 (most recent claim defined the index date), ≥1 HIV diagnosis within 1 year before index, age ≥18 years at first HIV diagnosis and <65 years at index, ≥12 months of continuous eligibility before index, and no history of HIV-2 infection. Comorbidities, concomitant medication use, and pill burden were assessed in the 4 years before index. Analyses were stratified by patient age and treatment experience.Results: Among 3456 patients, the mean (standard deviation [SD]) age was 47.1 (10.4) years; the majority were black (55%) and men (63%). In general, the prevalence of comorbidities increased from the fourth year to the first year before index and included cardiovascular disease (28-40%), hypertension (24-37%), hyperlipidemia (12-17%), and asthma/chronic obstructive pulmonary disease (13-19%). Concomitant medication use corresponding to these comorbidities slightly increased over time. In the year before index, mean (SD) daily pill burden was 2.1 (1.4) for ARVs and 5.9 (5.9) for non-ARVs. Older age and prior treatment experience were associated with higher rates of comorbidities and greater pill burden.Conclusions: In people with HIV infection, comorbidities and concomitant medication use increased with age, supporting considerations for streamlined ARV regimens highlighted in treatment guidelines.

Benchmarking HIV Quality Measures Across US Payer Types.

Despite advances in antiretroviral therapy (ART), human immunodeficiency virus (HIV) remains a significant issue in the United States. Early diagnosis, continuous treatment access/adherence, and long-term care engagement help patients benefit fully from ART; however, a shortfall in care engagement remains, potentially leading to poorer health outcomes. This analysis benchmarks rates of health care quality and process measures to identify areas for improvement. This retrospective, claims-based, real-world cohort study assessed the percentage of prevalent (existing) and incident (newly diagnosed) patients with HIV with commercial or public health insurance meeting 4 National Quality Forum (NQF)-endorsed, 1 Pharmacy Quality Alliance (PQA), and 3 Centers for Disease Control and Prevention (CDC) measures over a 4-year period. Most prevalent patients consistently met the NQF-endorsed prescribed ART and gaps in visits measures. Longer-term visit frequency measure rates were well below the 90% Joint United Nations Programme on HIV/AIDS target. Proportion of prevalent patients meeting each NQF-endorsed measure was maintained/increased with increasing age in 2015-2016. Substantially fewer incident patients than prevalent patients met NQF-endorsed measures across all measurement periods, particularly for visit frequency (32%-51%). PQA ART adherence was low (36%-73%). CDC receipt of care rates were high (83%-92%), whereas retention in care rates were low (67%-72%) among prevalent patients. For incident patients, linkage to care rates were consistently low (21%-44%). This study benchmarks current US HIV care engagement and highlights the need for improvement in early care engagement, ART adherence and long-term retention of care among patients with HIV.

Clinical characteristics and treatment patterns among US patients with HIV.

OBJECTIVES: Describe the clinical characteristics and treatment patterns of patients with HIV-1 who have commercial or Medicare health insurance in the United States. STUDY DESIGN: Retrospective cohort study. METHODS: Administrative claims for adult commercial and Medicare health plan enrollees with evidence of HIV-1 and antiretroviral therapy (ART) between January 1, 2007, and March 31, 2017, were assessed. Current and previous complete ART regimens were identified using a claims-based algorithm. Results were stratified by treatment status and insurance type. RESULTS: Of 18,699 eligible patients, 5027 (27%) had no previous ART regimens; 15,275 (82%) had commercial insurance. Mean age was 47.5 years. Common comorbidities included hyperlipidemia, cardiovascular disease, hypertension, depression, and anxiety. The mean number of ART regimens was 1.43, with 31% of patients having 2 or more regimens. Mean (SD) daily pill burden was higher in patients with more than 1 ART regimen over time (5.7 [6.0] pills) or with Medicare insurance (9.2 [8.0] pills) than in patients with no previous ART (1.9 [4.4] pills) or with commercial insurance (3.7 [4.7] pills). Overall, 60% of patients achieved 90% or greater adherence to their ART regimen and 16% had a prescription filled for any contraindicated medication to an ART during their regimen. CONCLUSIONS: This descriptive study demonstrated that people living with HIV enrolled in Medicare have a significant amount of comorbidities and total pill burden. Although advancements in ART have significantly improved life expectancy and quality of life for people living with HIV, it is important to take into account individual complexities such as comorbidities and pill burden when selecting ART regimens.

Real-World Health Plan Data Analysis: Key Trends in Medication Adherence and Overall Costs in Patients with HIV.

BACKGROUND: Adherence to effective antiretroviral therapy (ART) is essential to achieve long-term viral suppression in patients with HIV-1. Single-tablet regimens (STRs) have improved adherence and decreased health care costs and hospitalizations, but previous study results suggest that the relationship between ART adherence and health care costs and utilization is complex. OBJECTIVE: To assess ART adherence trends in patients with HIV-1 to determine if differences in utilization, demographics, and overall costs exist among patients with varying levels of medication adherence. METHODS: This retrospective study analyzed medical and pharmacy claims data from an administrative claims database between January 1, 2007, and June 30, 2016, for Medicaid or commercially insured patients continuously enrolled for ≥ 6 months before and ≥ 15 months after the index date (date of first medical claim with an HIV diagnosis or pharmacy claim for HIV ART medication between July 1, 2007, and June 30, 2014). Qualifying patients were aged ≥ 18 years with a diagnosis of HIV-1 infection or at least 1 pharmacy claim for HIV ART at index and at least 2 pharmacy claims during the follow-up period. Patients were categorized on the basis of adherence as measured by proportion of days covered (PDC; ≥ 95%, highly adherent; < 95%, less adherent) and treatment with an STR or multiple-tablet regimen (MTR). Commercially insured patients were stratified by duration of follow-up data (< 3 or ≥ 3 years). There were not enough Medicaid patients for follow-up analysis. Outcomes of interest were ART adherence and annual medical and pharmacy utilization and costs. Descriptive statistics were generated, and health care resource utilization and costs were reported as annual averages. Chi-square and t-tests were used to examine differences between the cohorts. RESULTS: A total of 332 Medicaid patients and 1,698 patients insured commercially met inclusion criteria. Adherence to ART medication (mean PDC) during the first 15 months was lower in Medicaid patients (65%) versus commercial patients (79%; P < 0.0001). Patients treated with STRs comprised 47% and 37% of patients in the < 3-year and ≥ 3-year follow-up cohorts, respectively. More STR patients achieved ≥95% adherence than MTR patients (< 3-year follow-up, 53% vs. 39%; ≥ 3-year follow-up, 61% vs. 45%; P < 0.001). In both follow-up cohorts, less adherent patients had higher mean annual medical costs, and results were significant for patients with ≥ 3-year follow-up ($8,224 vs. $3,097; P = 0.0007). These results were largely driven by savings in mean annual inpatient costs among the highly adherent patients in both cohorts (< 3-year follow-up, -$2,525 [P = 0.0003]; ≥ 3-year follow-up, -$815 [P < 0.001]). CONCLUSIONS: Patients on STRs were more adherent than patients on MTRs regardless of length of follow-up. Better adherence was associated with significant inpatient cost savings. The relationship between adherence and total medical costs is nuanced depending on the duration of follow-up. DISCLOSURES: This study was funded by ViiV Healthcare, which participated in protocol development, the analysis plan, and interpretation of results but did not have final approval on the decision to publish. Kangethe, Polson, Lord, and Evangelatos are employees of Magellan Rx Management, which was contracted by ViiV Healthcare to conduct the research for this study. Oglesby is an employee of ViiV Healthcare and owns stock in GlaxoSmithKline. Data from this study were previously presented at AMCP Nexus; October 16-19, 2017; Dallas, TX.

A Retrospective Administrative Claims Database Evaluation of the Utilization of Belimumab in US Managed Care Settings.

PURPOSE: Belimumab is an approved therapy for the treatment of systemic lupus erythematosus (SLE). This study examined the real-world utilization patterns of belimumab and standard SLE therapies in patients after regulatory approval of belimumab in the United States. METHODS: A retrospective, observational study of belimumab users in the HealthCore Integrated Research Database was conducted using administrative claims data (GlaxoSmithKline Clinical Study Register Study ID: 114955). The overall population for analysis was composed of patients who were prescribed belimumab, had ≥6 months pre- and ≥6 months post-index medical and pharmacy eligibility, and at least 1 medical claim for SLE. Patients' clinical and demographic characteristics, treatment history, treatment patterns of belimumab, utilization of other medications, all-cause resource utilization, and costs were assessed. No hypotheses were tested. FINDINGS: All patients who were prescribed belimumab had an SLE claim. Patients who met all eligibility criteria (n = 155) were primarily female (94.2%; mean [SD] age, 44 [12] years) and 94.2% had used standard SLE therapies during the pre- and post-index periods. The majority had moderate SLE disease severity pre-index, and there was a small shift (approximately 8%) from moderate to mild SLE after initiation of belimumab. Two thirds of patients remained on belimumab therapy at 6 months post-index. The percentage of patients with any claim for oral corticosteroids remained stable; however, the point estimate for mean daily dose decreased slightly in months 3 to 6 post-index. Inpatient hospital admissions decreased slightly in the post-index period. The point estimate for total costs (excluding belimumab) decreased after initiation of belimumab, although overall total health care costs (including belimumab) increased. IMPLICATIONS: All patients with a belimumab prescription had an SLE diagnosis on at least 1 medical claim, and the vast majority of those meeting all eligibility criteria had previously used a standard SLE therapy. Disease severity improved for a number of patients while on belimumab treatment and modest corticosteroid dose reductions were observed in later months. After initiating belimumab, health care costs (excluding belimumab) decreased. GlaxoSmithKline Clinical Study Register Study ID: 114955.

Costs, resource utilization, and treatment patterns for patients with metastatic melanoma in a commercially insured setting.

OBJECTIVE: To estimate real-world healthcare costs, resource utilization, and treatment patterns among metastatic melanoma (MM) patients who received a therapy recommended in current treatment guidelines during 2011 and 2012, following approval in the US of novel therapies (ipilimumab and vemurafenib). RESEARCH DESIGN AND METHODS: Administrative claims data were used in a retrospective, longitudinal, open cohort study. Adult MM patients were identified using ICD-9 codes. Therapy-based patient cohorts and index dates were defined by the first receipt of a therapy of interest: ipilimumab, vemurafenib, paclitaxel (alone and in combination), interleukin-2, dacarbazine (alone and in combination), or temozolomide. The follow-up period extended until the end of eligibility or data availability. A multivariate regression model was used to compare outcomes of the ipilimumab and vemurafenib cohorts, controlling for baseline and demographic characteristics. MAIN OUTCOME MEASURES: Direct healthcare costs (2013 US dollars) and utilization (incidence rates) were measured on a per-patient-per-month (PPPM) basis for each treatment cohort. Treatment patterns were assessed, including the frequency of patients receiving a second therapy of interest. RESULTS: The study population included 834 patients (265 ipilimumab, 234 vemurafenib, 174 paclitaxel, 104 interleukin-2, 46 dacarbazine, and 11 temozolomide). Costs ranged from $10,879 PPPM (temozolomide) to $35,472 PPPM (ipilimumab). Adjusted total costs were $18,337 PPPM higher for the ipilimumab vs. the vemurafenib cohort (p < 0.001), primarily due to higher outpatient costs. Multivariate analysis did not find significant differences in resource utilization between ipilimumab and vemurafenib, except that ipilimumab patients had fewer outpatient visits (excluding treatment visits). Ipilimumab and vemurafenib patients received a second therapy of interest (12% and 11%, respectively) less frequently than interleukin-2 and dacarbazine patients. CONCLUSIONS: The cost and resource utilization burden of MM is high and varies substantially across treatment cohorts. The two novel therapies, ipilimumab and vemurafenib, have quickly been adopted and are the most frequently used therapies. The results observed during the approximately 6 month follow-up period may not be representative of the full clinical experience of patients with MM.

Economic burden associated with adverse events in patients with metastatic melanoma.

BACKGROUND: There are currently many approved agents for the treatment of metastatic melanoma (MM), the most aggressive form of skin cancer. Treatments may include systemic therapies such as ipilimumab, dacarbazine, temozolomide, high-dose interleukin 2, interferon α, dacarbazine- or temozolomide-based combination chemotherapy/biochemotherapy, paclitaxel, paclitaxel/cisplatin, and paclitaxel/carboplatin, as well as the targeted therapies vemurafenib, dabrafenib, and trametinib for patients with BRAF V600 mutation. However, all treatment options are associated with different adverse events (AEs) and, in some instances, considerable toxicity. The occurrence of such treatment-related AEs can lead to higher health care resource utilization and increasing treatment and patient management costs. An understanding of the economic burden of these AEs will therefore enable better management of health care expenditures, not just for existing therapies, but also for new and novel treatments in development. OBJECTIVE: To estimate the incremental health care costs of specific AEs among patients with MM treated with paclitaxel, vemurafenib, ipilimumab, dacarbazine, temozolomide, high-dose interleukin 2, or interferon α, along with AEs known to be associated with dabrafenib and trametinib. METHODS: This cohort study employed a retrospective administrative claims-based analysis of MarketScan commercial and Medicare supplemental databases from July 1, 2004, to April 30, 2012. Patients included those aged ≥ 18 years who had diagnosed melanoma (ICD-9-CM code 172.xx)with ≥ 1 diagnosis of metastasis and ≥ 1 claim for any of the 7 study treatments. Health care encounters for AEs of interest were based on ICD-9-CM diagnosis/procedure codes. Incremental cost per AE was determined by comparing the 30-day expenditures in patients with the event to patients without the event based on a shadow event date. Multivariate generalized linear models (GLMs) with a log-link function and gamma distribution were utilized to control for baseline differences between groups. RESULTS: A total of 2,621 patients with MM were included. Mean age was 56.0 years (SD ± 13.0); 64% were male; and 24% had a diagnosis of primary or secondary brain cancer at the time of MM diagnosis. GLM-based estimate of 30-day incremental costs by AE category were metabolic, $9,135 (95% CI = $6,404-$12,392); hematologic/lymphatic, $8,450 (95% CI = $6,528-$10,633); cardiovascular, $6,476 (95% CI = $4,667-$8,541); gastrointestinal, $6,338 (95% CI = $4,740-$8,122); skin/subcutaneous, -$900 (95% CI = -$1,899-$237); central nervous system/psychiatric, $5,903 (95% CI = $3,842-$8,313); and pain, $5,078 (95% CI = $3,392-$7,012). CONCLUSIONS: Incremental costs associated with many MM treatment-related AEs are substantial. New approaches to prevent and/or better manage these events may reduce overall health care costs.

Impact of early versus late systemic lupus erythematosus diagnosis on clinical and economic outcomes.

BACKGROUND AND OBJECTIVES: Systemic lupus erythematosus (SLE) is a multisystem complex autoimmune disease that often mimics symptoms of other illnesses, which complicates the ability of healthcare providers to make the diagnosis. The objective of this study was to assess clinical outcomes, resource utilization, and costs between patients with earlier versus later SLE diagnosis. METHODS: Patients aged 18-64 years were identified from a large US commercial claims database between January 2000 and June 2010. Confirmed SLE diagnosis with a claims-based algorithm required either three or more claims for a visit to a rheumatologist on separate dates with an SLE diagnosis (International Classification of Diseases [ICD-9] code 710.0x), two or more claims for visits to a rheumatologist at least 60 days apart with SLE diagnoses, or two or more claims for visits to rheumatologist less than 60 days apart with SLE diagnoses with at least one dispensing for a typical SLE medication. SLE probable onset date was identified during the 12-month baseline period by the second claim for antinuclear antibody tests or prodromal symptoms of SLE. Patients were stratified into early or late diagnosis groups based on time between probable SLE onset and diagnosis (<6 months or ≥6 months, respectively). Each patient observation period began on the date of the first medical claim, with a diagnosis code for SLE that satisfied the inclusion criteria, and ended on the earliest date between health plan disenrollment and 30 June 2010. Patients in each group were propensity-score matched on age, gender, diagnosis year, region, health plan type, and comorbidities. Flare rates and resource utilization were compared post-diagnosis between groups using rate ratios. All-cause and SLE-related costs (adjusted to 2010 US dollars) per patient per month (PPPM) were calculated. RESULTS: There were 4,166 matched patients per group. Post-SLE diagnosis, the early diagnosis group had lower rates of mild (rate ratio [RR] 0.95; 95 % CI 0.93-0.96), moderate (RR 0.96; 95 % CI 0.94-0.99), and severe (RR 0.87; 95 % CI 0.82-0.93) flares compared with the late diagnosis group. The rates of hospitalizations (RR 0.80; 95 % CI 0.75-0.85) were lower for the early diagnosis group than the late diagnosis group. Compared with late diagnosis patients, mean all-cause inpatient costs PPPM were lower for the early diagnosis patients (US$406 vs. US$486; p = 0.016). Corresponding SLE-related hospitalization costs were also lower for early compared with late diagnosis patients (US$71 vs. US$95; p = 0.013). Results were consistent for other resource use and cost categories. CONCLUSIONS: Patients diagnosed with SLE sooner may experience lower flare rates, less healthcare utilization, and lower costs from a commercially insured population perspective. This finding needs to be further explored within the context of background SLE disease activity.

Direct and indirect costs among employees with diabetic retinopathy in the United States.

OBJECTIVE: To examine, from the employer perspective, the direct (healthcare) and indirect (workloss) costs of employees with diabetic retinopathy (DR) compared to control non-DR employees with diabetes, and within DR subgroups. METHODS: Compared annual costs using claims data from 17 large companies (1999-2004). 'DR employees' (n = 2098) had >or= 1 DR (International Classification of Disease, 9th Revision [ICD-9]) diagnosis; DR subgroups included employees with diabetic macular edema (DME), proliferative DR (PDR), and employees receiving photocoagulation or vitrectomy procedures. Descriptive and multivariate tests were performed. RESULTS: DR employee annual direct costs were $18,218 (indirect = $3548) compared to $11,898 (indirect = $2374) for controls (Delta = $2032 (adjusted); p < 0.0001). Costs differences were larger across DR employee subgroups: DME/non-DME ($28,606/$16,363); PDR/non-PDR ($30,135/$13,445; p < 0.0001); DR with/without photocoagulation ($34,539/$16,041; p < 0.0001); and DR with/without vitrectomy ($63,933/$17,239; p < 0.0001). LIMITATIONS: This study examined the incremental costs of treating DR employees, which may be higher than the incremental costs of DR itself. Some measures of diabetes severity (e.g., duration of diabetes) were not available in the claims data, and were therefore not included in the multivariate models. The cost of photocoagulation and vitrectomy procedures pertain to individuals who underwent these procedures, and not the cost of the procedures themselves. CONCLUSION: DR employees had significantly higher costs than controls, and larger differences existed within DR subgroups. Indirect costs accounted for about 20% of total cost.

Estimating the long-term cost-effectiveness of exenatide in the United States: an adjunctive treatment for type 2 diabetes mellitus.

OBJECTIVES: This analysis provides an early estimate of the cost-effectiveness of adjunctive exenatide in treating type 2 diabetes mellitus in the United States. Data from pivotal phase III 30-week clinical trials and 52 weeks of their subsequent open-label extension studies (i.e., 82 weeks total) were used to project the effects of 30 years of adjunctive exenatide treatment. METHODS: This analysis utilized a published and validated Markov model incorporating Monte Carlo simulation with tracker variables to estimate the clinical and cost outcomes of adding exenatide to a background of metformin and/or sulfonylurea treatment, with the effects of 30 years of adjunctive exenatide treatment (projected from data from 82 weeks of exenatide treatment) compared with no additional treatment beyond metformin and/or a sulfonylurea. Sensitivity analyses were performed on key clinical assumptions, discount rates, and shorter time horizons. RESULTS: The base-case scenario (30 years of exenatide) yielded an incremental cost-effectiveness ratio (ICER) of $35,571. We found that shortening the time horizons and removing the lipid effects of exenatide had the greatest negative impact on ICERs when performing sensitivity analysis. CONCLUSIONS: Our analysis demonstrated that exenatide used for 20 or 30 years compared with no additional treatment beyond metformin and/or a sulfonylurea is cost-effective in the adjunctive treatment of type 2 diabetes with an ICER less than $50,000 per life-year gained. Sensitivity analyses suggest that, in addition to sustained reduction in HbA(1c), the added clinical effects of improved lipid values, systolic blood pressure, and reduced body mass index all positively contributed to the cost-effectiveness of exenatide.

The association between diabetes related medical costs and glycemic control: a retrospective analysis.

BACKGROUND: The objective of this research is to quantify the association between direct medical costs attributable to type 2 diabetes and level of glycemic control. METHODS: A longitudinal analysis using a large health plan administrative database was performed. The index date was defined as the first date of diabetes diagnosis and individuals had to have at least two HbA1c values post index date in order to be included in the analyses. A total of 10,780 individuals were included in the analyses. Individuals were stratified into groups of good (N = 6,069), fair (N = 3,586), and poor (N = 1,125) glycemic control based upon mean HbA1c values across the study period. Differences between HbA1c groups were analyzed using a generalized linear model (GLM), with differences between groups tested by utilizing z-statistics. The analyses allowed a wide range of factors to affect costs. RESULTS: 42.1% of those treated only with oral agents, 66.1% of those treated with oral agents and insulin, and 57.2% of those treated with insulin alone were found to have suboptimal control (defined as fair or poor) throughout the study period (average duration of follow-up was 2.95 years). Results show that direct medical costs attributable to type 2 diabetes were 16% lower for individuals with good glycemic control than for those with fair control ($1,505 vs. $1,801, p < 0.05), and 20% lower for those with good glycemic control than for those with poor control ($1,505 vs. $1,871, p < 0.05). Prescription drug costs were also significantly lower for individuals with good glycemic control compared to those with fair ($377 vs. $465, p < 0.05) or poor control ($377 vs. $423, p < 0.05). CONCLUSION: Almost half (44%) of all patients diagnosed with type 2 diabetes are at sub-optimal glycemic control. Evidence from this analysis indicates that the direct medical costs of treating type 2 diabetes are significantly higher for individuals who have fair or poor glycemic control than for those who have good glycemic control. Patients under fair control account for a greater proportion of the cost burden associated with antidiabetic prescription drugs.

Review of the cost of diabetes complications in Australia, Canada, France, Germany, Italy and Spain.

OBJECTIVES: To provide a comprehensive source document on previously published cost data for diabetic complications in Australia, Canada, France, Germany, Italy and Spain for use in a peer-reviewed, validated diabetes model. METHODS: A search for published cost of diabetes complications data was performed in peer-reviewed journals listed in PubMed and health economic conference proceedings from 1994 to March 2005. Where country specific data were not available, we referred to government websites and local cost experts. All costs were inflated to 2003 Euros (E). Major complication costs are presented. RESULTS: First year costs of non-fatal myocardial infarction varied between E19277 in Spain and E12292 in Australia. In subsequent years of treatment, this range was E1226 (France) to E203 (Australia). Angina costs were similar across all four countries: E1716 in Australia; E2218 in Canada; E2613 in France; E3342 in Germany; E2297 in Italy; and E2207 in Spain. Event costs of non-fatal stroke were higher in Canada (E23173) than in other countries (Australia E13443; France E11754; Germany E19399; Italy E6583; Spain E4638). Event costs of end-stage renal disease varied depending on the type of dialysis: in Australia (E17188-27552); Canada (E33811-58159); France (E24608-56487); Germany (E46296-68175); Italy (E43075-56717); and Spain (E28370-32706). Lower extremity amputation costs were: E18547 (Australia); E17130 (Canada); E31998 (France); E22096 (Germany); E10177 (Italy); and E14787 (Spain). CONCLUSIONS: Overall, our search showed costs are well documented in Australia, Canada, France and Germany, but revealed a paucity of data for Spain and Italy. Spanish costs, collected by contacting local experts and from government reports, generally appeared to be lower for treating cardiovascular complications than in other countries. Italian costs reported in the literature were primarily hospitalization costs derived from diagnosis-related groups, and therefore likely to misrepresent the cost of specific complications. Additional research is required to document complication costs in Spain and Italy. Australian and German values were collected primarily by referring to diagnostic related group (DRG) tariffs and, as a result, there may be a need for future economic evaluations measuring the accuracy of the costs and resource utilization in the reported values. These cost data are essential to create models of diabetes that are able to accurately simulate the cumulative costs associated with the progression of the disease and its complications.

Relationship of glycemic control to total diabetes-related costs for managed care health plan members with type 2 diabetes.

OBJECTIVE: Glycosylated hemoglobin (A1c) is a well-established measure of glycemic control, and evidence suggests that maintaining an acceptable A1c level may be associated with lower treatment costs in adults with diabetes. Understanding the impact on total treatment costs of staying at the target A1c level is of great importance to managed care organizations. The goal of this study was to determine whether type 2 diabetes patients at or below the target A1c level of 7% had lower diabetes-related costs compared with patients above an A1c level of 7%. METHODS: This study was a retrospective database analysis using eligibility data, medical and pharmacy claims data, and laboratory data from a large U.S. health care organization. Patients were included in the study if they had 2 or more claims for type 2 diabetes (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 250.x0 or 250.x2) and at least 1 A1c value (first such date defined as the index date) during the 12-month period from January 1, 2002, through December 31, 2002. Patients with 2 or more medical claims for type 1 diabetes (ICD-9-CM codes 250.x1 or 250.x3) were excluded from the study. Study patients were divided into 2 groups, those at the target A1c level (7%) and those at the above-target A1c level (>7%), and were followed for a period of 1 year after their index date. Demographic, clinical, and cost variables were extracted from the administrative database. Multiple linear regression analysis was used to compare treatment costs between patients at the target A1c level and patients above target level. RESULTS: A total of 3,121 patients (46.0%) were identified as being at the target A1c level, and 3,659 patients (54%) were identified as being above the target A1c level during the study period. After controlling for confounding factors, the predicted total diabetes-related cost for the above-target group during the 1-year follow-up period was 1,540 US dollars per patient, 32% higher than the total diabetes-related cost (1,171 US dollars) for the at-target group (P <0.001). CONCLUSION: Results of this analysis suggest that managed care members with type 2 diabetes who stayed continuously at the target A1c level of 7% or less over a 1-year follow-up period incurred lower diabetes-related costs compared with managed care members with type 2 diabetes who were continuously over the target A1c level of 7%.

Impact of changes in HbA1c, lipids and blood pressure on long-term outcomes in type 2 diabetes patients: an analysis using the CORE Diabetes Model.

OBJECTIVES: Various factors influence the risk of complications in type 2 diabetes patients. The isolated impact of single risk factors on long-term outcomes is unclear. The aim of this study was to calculate the projected effects on life expectancy (LE), quality-adjusted LE (QALE) and total costs of complications (TC) of 10% improvements in baseline levels of either total cholesterol (T-CHOL), high-density lipoprotein cholesterol (HDL), systolic blood pressure (SBP), glycosylated haemoglobin (HbA1c), and all four parameters combined. METHODS: A cohort of newly diagnosed patients (baseline age 52 years, HbA1c 9.1%, SBP 137 mmHg, T-CHOL 212 mg/dL, and HDL 39 mg/dL) was defined. The CORE Diabetes Model was used to simulate LE, QALE and TC (US third-party payer perspective discounted at 3% annually) over patients' lifetimes, assuming no change in risk factors, an isolated 10% improvement in each parameter, or a 10% improvement in all parameters simultaneously. RESULTS: Improved HbA1c led to increases in LE and QALE of 1.00 and 0.81 years respectively, and decreased TC of (US) 10,800 dollars/patient. Improved SBP led to improvements in LE and QALE of 0.67 and 0.55 years respectively and decreased TC of 7,049 dollars. Decreased T-CHOL led to improvements in LE and QALE of 0.29 and 0.20 years, respectively, and increased TC of 1,923 dollars. Increased HDL led to improvements in LE and QALE of 0.28 and 0.18 years respectively, and increased TC of 2,162 dollars. Simultaneous improvements in all parameters led to projected improvements in LE and QALE of 2.17 and 1.72 years respectively, and decreased TC of 14,533 dollars. CONCLUSIONS: Combined improvements in HbA1c, lipid levels and SBP produced the greatest benefits in terms of LE, QALE and TC. A 10% improvement in HbA1c had the greatest impact on these three outcomes.

What impact would pancreatic beta-cell preservation have on life expectancy, quality-adjusted life expectancy and costs of complications in patients with type 2 diabetes? A projection using the CORE Diabetes Model.

OBJECTIVE: Type 2 diabetes is characterised by progressive failure of pancreatic beta-cell function against a background of insulin resistance. Multifactorial interventions, including intensive glycaemic and blood pressure control, reduce the risk of onset and progression of complications. However, current management of type 2 diabetes focuses on treatment of signs and symptoms of disease instead of targeting underlying causes. A number of newer pharmacological interventions, including thiazolidinediones and glucagon-like peptides, have shown early promise in preserving pancreatic beta-cell function. The aim of this study was to investigate the impact of stabilising beta-cell function on long-term outcomes in patients with type 2 diabetes. METHODS: The CORE Diabetes Model was used to project life expectancy (LE), quality-adjusted LE (QALE) and total lifetime complication costs (TC) for a cohort of newly-diagnosed patients with type 2 diabetes, either with a typical increase of HbA1c over time as observed in the UKPDS, or assuming stabilisation of HbA1c after diagnosis with a hypothetical new treatment, representing beta-cell function stabilisation. Costs due to diabetes-related complications (from a US third-party payer perspective), were discounted at 3% annually. Both non-discounted and discounted (at 3% annually) LE and QALE were calculated. Sensitivity analyses were performed to test the robustness of results. RESULTS: Over a time period of 50 years, in a cohort with no increase of HbA1c over time, LE and QALE were improved by mean (SD) 1.02 (0.36) and 0.96 (0.25) years, and total costs of complications were reduced by 6,377 dollars (2,568) per patient compared to the cohort with a typical increase in HbA1c over time. Results were robust under a wide range of plausible assumptions. CONCLUSIONS: New interventions that stabilise pancreatic betacell function may have an important impact on length and quality of life, and lead to reduced costs of complications in patients with type 2 diabetes.

The health care costs of diabetic nephropathy in the United States and the United Kingdom.

PROBLEM: Diabetic nephropathy (DN) is a common microvascular complication of diabetes and can result in end-stage renal disease (ESRD) necessitating long-term dialysis or kidney transplantation. The costs of these complications are relatively high. The aim of this study was to quantify and compare the rates and annual costs of DN in the USA and the UK. METHODS: A cost of illness model was used to estimate the numbers of people with DN (microalbuminuria, overt nephropathy, and ESRD) or a previous kidney transplant at a given point in time and the numbers of new kidney transplants during a year. All costs were estimated in 2001 currencies. A sensitivity analysis assessed the robustness of the national annual cost estimates. RESULTS: In the USA, the total annual medical costs incurred by all payers in managing DN were US dollars 1.9 billion for Type 1 diabetes (range: US dollars 1.0-2.8 billion), US dollars 15.0 billion for Type 2 diabetes (range: US dollars 7.6-22.4 billion), and US dollars 16.8 billion for all diabetes (range: US dollars 8.5-25.2 billion). In the UK, the total annual costs to the National Health Service (NHS) of managing DN were US dollars 231 million ( pound 152 million) for Type 1 diabetes (range: US dollars 190-350 million [ pound 125-230 million]), US dollars 933 million (pound 614 million) for Type 2 diabetes (range: US dollars 809 million-US dollars 1.4 billion [pound 532-927 million]), and US dollars 1.2 billion ( pound 765 million) for all diabetes (range: US dollars 999 million-US dollars 1.8 billion [pound 657 million- pound 1.2 billion]). CONCLUSIONS: The total annual cost of DN is 13 times greater in the USA than in the UK. Controlling for the substantially higher number of people at risk, the total cost per person with DN and/or a kidney transplant is 40% higher: US dollars 3735 in the USA and US dollars 2672 (pound 1758) in the UK.