Lemborexant and Daridorexant for the Treatment of Insomnia: An Indirect Comparison Using Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed.

Objective: To determine if there are differences in the number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH) between lemborexant and daridorexant and to compare lemborexant with daridorexant indirectly.Methods: Dichotomous efficacy and tolerability outcomes reported for Phase 3 daridorexant trials (conducted May 29, 2018-May 14, 2020) for months 1 and 3 were identified from published literature and regulatory documents. Analogous data were extracted for lemborexant from Phase 3 studies (conducted May 31, 2016-January 8, 2019). NNT, NNH, and LHH were then calculated.Results: Lemborexant 5 mg and 10 mg had clinically relevant therapeutic effect sizes, evidenced by most NNT values versus placebo < 10 for Insomnia Severity Index [ISI], subjective total sleep time [sTST], and polysomnography outcomes. NNH values for adverse events (AEs) were > 10, suggesting relative tolerability. Somnolence was the most common AE. Discontinuation rates of lemborexant because of an AE were low, including for somnolence. Efficacy outcomes for daridorexant 25-mg and 50-mg doses pooled resulted in most NNT values versus placebo ≥ 10, with more robust NNT estimates for the 50-mg dose than for the 25-mg dose. Discontinuation rate because of an AE at month 3 was higher for placebo than for daridorexant, rendering favorable LHH calculations. Daridorexant evidenced low rates of somnolence or fatigue.Conclusions: In Phase 3 trials, the benefit-risk ratios for both lemborexant and daridorexant were favorable as measured by NNT, NNH, and LHH. Indirect comparisons of lemborexant with daridorexant suggest an efficacy advantage for lemborexant and a tolerability advantage for daridorexant.Clinical Trials Registration: NCT02783729, NCT02952820, NCT03545191, NCT03575104.

Economic burden of comorbid insomnia in 5 common medical disease subgroups.

STUDY OBJECTIVES: Approximately 85% of insomnia co-occurs with other disorders. Whereas insomnia was once considered "secondary" to these disorders, it is now widely recognized as an independent condition warranting treatment. While it is clear that insomnia can affect the course of other medical conditions, there is scant literature on the economic impact of comorbid insomnia among patients with common medical conditions. The aim of this study was to determine the economic burden of comorbid insomnia in 5 medical diseases commonly associated with insomnia: type 2 diabetes mellitus (T2DM), cancer undergoing treatment, menopause undergoing hormone replacement therapy, osteoporosis, and Alzheimer's disease and related dementias (ADRDs). METHODS: This retrospective cohort study used claims data from the IBM MarketScan Commercial and Medicare Supplemental Databases from January 1, 2014, through December 31, 2019. Insomnia and comorbid disease groups were defined using physician-assigned International Classification of Diseases diagnostic codes. Insomnia medication treatment was defined based on ≥1 prescription fills for the most commonly prescribed insomnia medications (zolpidem, low-dose trazodone, and benzodiazepines [as a class]). For each comorbid disease subgroup, 4 cohorts were created: (1) patients with either treated or untreated insomnia, (2) non-sleep-disordered controls, (3) patients with untreated insomnia, and (4) patients with treated insomnia. RESULTS: Sample sizes for individuals with comorbid insomnia ranged from 23,168 (T2DM) to 3,015 (ADRDs). Within each disease subgroup and relative to non-sleep-disordered controls, patients with comorbid insomnia demonstrated greater adjusted health care resource utilization and costs across most points of service. Likewise, relative to individuals with untreated insomnia, those with treated insomnia generally demonstrated greater adjusted health care resource utilization and costs. CONCLUSIONS: In this national analysis, both untreated comorbid insomnia and comorbid insomnia treated with commonly prescribed insomnia medications were associated with increased health care resource utilization and costs across most points of service. CITATION: Wickwire EM, Juday TR, Kelkar M, Heo J, Margiotta C, Frech FH. Economic burden of comorbid insomnia in 5 common medical disease subgroups. J Clin Sleep Med. 2023;19(7):1293-1302.

Benzodiazepine Usage, Healthcare Resource Utilization, and Costs Among Older Adults Treated with Common Insomnia Medications: A Retrospective Cohort Study.

Background: Benzodiazepines are commonly prescribed for insomnia management but are often associated with negative safety outcomes such as falls and abuse, particularly among older adults. Objective: The purpose of this real-world study was to compare the impact of benzodiazepines, low-dose trazodone, and zolpidem immediate release (IR) on healthcare resource utilization (HCRU), and costs among older adults (age ≥ 65 years) with insomnia in the US. Methods: Using the IBM MarketScan Medicare Supplemental Database, older adults with >1 physician-assigned diagnosis of insomnia and treated with benzodiazepines were matched 1:1 on age, sex, and index-date to individuals treated with trazodone, and separately matched 1:1 on age and sex, to individuals treated with zolpidem immediate release (IR). Between-groups differences were analyzed using general linear models (GLMs) that controlled for multiple confounders. Results: Significant between-groups differences in HCRU and costs were observed such that relative to zolpidem IR and separately relative to low-dose trazodone, benzodiazepines were consistently associated with worsened outcomes. Conclusion: These findings build upon and extend prior knowledge on the negative impact of benzodiazepines and suggest directions for future research.

Cardiac events and economic burden among patients with hypertension and treated insomnia in the USA.

Background: Cardiovascular (CV) event risk, healthcare resource utilization (HCRU) and costs have not been elucidated among hypertension patients with treated insomnia (H + TI). Materials & methods: Adult patients with H + TI were identified in IBM MarketScan databases. H + TI patients were matched 1:1 on age and sex to controls with hypertension but without sleep disorders. Multivariable models were used to estimate associations between treated insomnia and CV event risk, HCRU and costs. Results: In total, 81,502 H + TI patients (mean age = 62 years, 53% female) were matched. Relative to controls, H + TI patients were 2.4 times as likely to have CV events. H + TI patients incurred higher costs per patient per month (US$2343 vs US$1013). Conclusion: Treated insomnia was associated with higher costs and HRCU in hypertension patients.

Falls, healthcare resources and costs in older adults with insomnia treated with zolpidem, trazodone, or benzodiazepines.

BACKGROUND: Falls are the leading cause of injury-related death among older Americans. While some research has found that insomnia heightens falls, health care resource utilization (HCRU) and costs, the impact of insomnia treatments on fall risk, mortality, HCRU and costs in the elderly population, which could be of substantial interest to payers, has not been fully elucidated. This study evaluated the risk of falls and related consequences among adults ≥ 65 years of age treated with common prescription medications for insomnia compared with non-sleep disordered controls. METHODS: This was a retrospective cohort analysis of deidentified Medicare claims from January 2011 through December 2017. Medicare beneficiaries treated for insomnia receiving zolpidem extended-release, zolpidem immediate-release, trazodone, or benzodiazepines were matched with non-sleep disordered controls. The main outcomes were falls, mortality, healthcare resource utilization (HCRU), and medical costs during the 12 months following the earliest fill date for the insomnia medication of interest. Generalized linear models controlled for several key covariates, including age, race, sex, geographic region and Charlson Comorbidity Index score. RESULTS: The study included 1,699,913 Medicare beneficiaries (59.9% female, mean age 75 years). Relative to controls, adjusted analyses showed that beneficiaries receiving insomnia medication experienced over twice as many falls (odds ratio [OR] = 2.34, 95% CI: 2.31-2.36). In adjusted analyses, patients receiving benzodiazepines or trazodone had the greatest risk. Crude all-cause mortality rates were 15-times as high for the insomnia-treated as controls. Compared with controls, beneficiaries receiving insomnia treatment demonstrated higher estimated adjusted mean number of inpatient, outpatient, and emergency department visits and longer length of inpatient stay. All-cause total adjusted mean costs were higher among insomnia treated patients ($967 vs $454). CONCLUSIONS: Individuals receiving insomnia treatment had an increased risk of falls and mortality and higher HCRU and costs compared with matched beneficiaries without sleep disorders. Trazodone and benzodiazepines were associated with the greatest risk of falls. This analysis suggests that significant risks are associated with common, older generation insomnia medication treatments in the elderly. Nonetheless, these results should be interpreted with caution as the use of these medications may be indicative of underlying morbidity with potential for residual confounding.

Incremental health care resource use and costs among adult patients with depression and treated for insomnia with zolpidem, trazodone, or benzodiazepines.

OBJECTIVE: To quantify health care resource utilization (HCRU) and costs associated with insomnia treated with commonly prescribed insomnia medications among patients with depression. METHODS: A retrospective cohort study was conducted using IBM MarketScan Commercial and Medicare Supplemental Databases to identify adults with: (1) ≥1 ICD-9/ICD-10 code for depression; (2) ≥1 commonly prescribed medication for insomnia (zolpidem immediate release [IR], zolpidem extended release [ER], trazodone, or benzodiazepines); and (3) ≥12 months of eligibility before and after initiating insomnia medication. A 1:1 age- and sex-matched control cohort with depression but without sleep-related disorders was identified. Adjusted HCRU and costs were compared using generalized linear models. RESULTS: A total of 21,027 patients (mean age = 48.3 years, 69.5% female) with depression and treated insomnia (D + TI; 1.9% zolpidem ER, 32.0% zolpidem IR, 50.0% trazodone, 16.1% benzodiazepines) were matched to controls. Although mean number of inpatient visits were similar (0.1 for both), relative to controls, D + TI had a higher mean number of ED (0.2 vs 0.1, p < .001) and outpatient visits (2.2 vs 1.3, p < .001). Adjusted total costs per patient per month were higher among D + TI patients ($2450 vs $1095, p < .001). Inpatient and ED costs were higher among patients prescribed zolpidem IR, trazodone, or benzodiazepines, but not zolpidem ER. CONCLUSIONS: Relative to controls with depression but without sleep disorders, overall, health care costs for adults with D + TI were 2.2-fold higher; costs and HCRU varied by insomnia medication. Further study of the impact of newer insomnia treatments on patient outcomes in depression and comorbid insomnia is warranted.

Fall Risk, Healthcare Resource Use, and Costs Among Adult Patients in the United States Treated for Insomnia with Zolpidem, Trazodone, or Benzodiazepines: A Retrospective Cohort Study.

INTRODUCTION: Falls are a common cause for morbidity and mortality among patients taking prescription insomnia medication. The objective of this study is to compare the risk of falls, all-cause healthcare resource utilization (HCRU), and costs among patients treated with commonly used, older generation insomnia medications and non-sleep-disordered controls. METHODS: This retrospective cohort study used the IBM® MarketScan® Commercial and Medicare Supplemental Databases to identify patients aged at least 18 years treated with commonly prescribed medications for insomnia (zolpidem, trazodone, benzodiazepines) between 1 January 2012 and 30 September 2017. The insomnia-treated cohort were age- and sex-matched (1:1) to non-sleep-disordered controls. Odds ratios (ORs) compared risk of falls in each cohort, adjusting for covariates. Costs were adjusted to 2018 dollars, the most recent year for the study data. RESULTS: Relative to matched controls (n = 313,086), the insomnia-treated cohort had a higher rate of falls (3.34% vs. 1.33%), and higher risk of falls [OR = 2.36 (95% confidence interval 2.27-2.44)]. Relative to other index treatments, patients treated with trazodone had the greatest risk of falls. Compared with matched controls, the estimated mean number of inpatient visits, emergency department visits, outpatient visits, and mean length of inpatient stay were all significantly higher among patients treated for insomnia. Such patients incurred greater total costs per patient per month than matched controls ($2100 versus $888; estimated mean ratio, 2.36; 95% CI 2.35-2.38; p < 0.0001). CONCLUSIONS: Relative to matched controls, the insomnia-treated cohort showed higher risk of falls with greater HCRU and costs. Each outcome measured was highest among patients treated with trazodone, relative to other index treatments. Findings suggest the need for new treatment options to optimize quality of care for patients with insomnia.

Lemborexant for the Treatment of Insomnia: Direct and Indirect Comparisons With Other Hypnotics Using Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed.

Objective: To describe lemborexant for the treatment of insomnia (DSM-5) in adults using number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).Methods: Lemborexant data were obtained from two Phase 3 trials conducted 2016-2018. Efficacy was assessed using different categorical definitions for response, and tolerability was assessed by evaluating rates of adverse events (AEs). Direct comparisons were made with zolpidem extended release (ER), and indirect comparisons were made with other hypnotic agents, including suvorexant, doxepin, ramelteon, zolpidem immediate release, eszopiclone, zaleplon, and selected benzodiazepines, using data from published reports and regulatory documents.Results: Lemborexant had a clinically relevant magnitude of therapeutic effect, as evidenced by NNT values versus placebo as robust as 3 (95% CI, 2-3). In general, NNH values for lemborexant versus placebo were ≥ 10, suggesting that lemborexant is relatively tolerable. Somnolence was the most common AE, with NNH estimates of 28 (95% CI, 18-61) and 15 (95% CI, 11-22) for lemborexant 5 mg and 10 mg, respectively. Rates of discontinuation of lemborexant because of an AE were low, and for lemborexant 5 mg the rate was lower than that for placebo. LHH contrasting the statistically significant endpoint efficacy measures versus discontinuation because of an AE ranged from 13 to 54. NNT values for lemborexant were generally more robust than for zolpidem ER for the polysomnography and sleep diary outcomes. In indirect comparisons, NNT data for the other hypnotics demonstrated effect sizes that were generally similar to those for lemborexant.Conclusions: In Phase 3 trials, the benefit-risk ratio for lemborexant is favorable as measured by NNT, NNH, and LHH.Trial Registration: ClinicalTrials.gov identifiers: NCT02783729, NCT02952820.

Challenges and opportunities in insomnia disorder.

BACKGROUND: Insomnia disorder is a prevalent, often unrecognized condition that affects millions. This clinical disorder is characterized by difficulty initiating or maintaining sleep over a sustained period. In fact, insomnia disorder affects much more than sleep; it increases the risk of developing serious medical and psychiatric comorbidities and can exacerbate existing conditions. The association between insomnia disorder and serious medical and psychiatric comorbidities are complex and directionality is not yet fully understood. There remain gaps in the treatment landscape for insomnia disorder. METHODS: We performed a narrative review of the published literature to identify challenges, unmet needs, and burden associated with insomnia disorder. RESULTS: In this article, we describe the substantial burden that insomnia disorder poses on patients, the healthcare system, and society in the US. This article explores the factors attributable to this burden including limited provider knowledge, inadequate treatment options, and unknown long-term impacts of off-label treatments. CONCLUSIONS: Several recommendations are proposed to address these challenges and improve patient outcomes through efforts to: (1) establish the societal value of treatment; (2) improve the clinical understanding of insomnia disorder; and (3) prioritize development of and access to effective treatments that do not pose addiction potential or tolerability issues.

Costs, exacerbations and pneumonia after initiating combination tiotropium olodaterol versus triple therapy for chronic obstructive pulmonary disease.

Aim: To compare health plan-paid costs, exacerbations and pneumonia outcomes for patients with chronic obstructive pulmonary disease (COPD) initiating combination tiotropium olodaterol (TIO + OLO) versus triple therapy (TT: long-acting muscarinic antagonist + long-acting ß2 agonists + inhaled corticosteroid). Patients & methods: COPD patients initiating TIO + OLO or TT between 1 January 2014 and 30 June 2016 were identified from a managed care Medicare database and balanced for baseline characteristics using inverse probability of treatment weighting before assessment of outcomes. Results: Annual COPD-related and all-cause costs were US$4118 (35%) and US$5384 (23%) lower for TIO + OLO versus TT (both p ≤ 0.001). TIO + OLO patients had nearly half the severe exacerbations (8.3 vs 15.5%; p = 0.014) and pneumonia was also less common (18.9 vs 30.9%; p < 0.001). Conclusion: TIO + OLO was associated with improved economic and COPD health outcomes versus TT.

Comparative effectiveness of single versus multiple tablet antiretroviral therapy regimens in clinical HIV practice.

We determined risk of virologic failure (VF) in individuals initiating tenofovir/emtricitabine/efavirenz as single versus multiple tablet regimens (MTR). We found no significant difference in the risk of VF, though did observe a trend toward more VF and M184 V mutations among persons initiating MTR. Temporal trends in care may have confounded results.

Public health impact of comprehensive hepatitis C screening and treatment in the French baby-boomer population.

OBJECTIVE: To estimate the public health impact of comprehensive hepatitis C virus (HCV) screening and access to all-oral, interferon (IFN)-free direct-acting antivirals (DAAs) in the French baby-boomer population (1945-1965 birth cohorts). METHODS: A sequential, multi-cohort, health-state transition model was developed to assess the impact of different hepatitis C screening and treatment strategies on clinical and economic outcomes in the 1945-1965 birth cohorts. Patients newly-diagnosed with chronic HCV were projected each year from 2016 to 2036 under three screening scenarios (70% [low], 75% [intermediate], and 80% [high] HCV awareness in 2036). Healthcare costs and clinical outcomes (number of liver-related deaths, quality-adjusted life-years [QALYs], life-years [LYs] spent in sustained virologic response [SVR] or with decompensated cirrhosis, hepatocellular carcinoma, or liver transplant) were compared among five treatment strategies (no antiviral therapy; IFN + ribavirin + protease inhibitor for fibrosis stages F2-F4, IFN-based DAAs for stages F2-F4, IFN-free DAAs for stages F2-F4, and IFN-free DAAs for stages F0-F4). RESULTS: Diagnosis of HCV genotype 1 was projected for 4,953, 6,600, and 8,368 individuals in the low, intermediate, and high screening scenarios, respectively. In the intermediate scenario, IFN-free DAAs for stages F0-F4 had a favorable cost-effectiveness profile vs IFN-based or IFN-free treatment strategies for F2-F4 and offered the greatest return on investment (0.899 LYs gained in SVR and 0.933 QALYs per €10,000 invested). CONCLUSION: Comprehensive HCV screening and access to all-oral, IFN-free DAAs is a cost-effective strategy that could help diminish the upcoming burden of HCV in the French baby-boomer population.

The wider public health value of HCV treatment accrued by liver transplant recipients.

OBJECTIVES: Organs for transplantation are scarce, but new medical therapies can prevent organ failure and the need for transplants. We sought to describe the unique value created by treatments that spare organs from failure and thus conserve donated organs for transplant into others, using hepatitis C virus (HCV) as a case study. STUDY DESIGN: Epidemiologic-economic model. METHODS: Using data on trends in chronic liver disease, liver disease progression, and liver transplant allocation models, as well as the effectiveness of new HCV treatments, we estimate the potential effects of systematic HCV screening and treatment on the demand for liver transplants in the United States. We estimate the spillover benefits to patients with all-cause liver disease in terms of increased availability of transplants and life-years gained. RESULTS: We estimated that systematic HCV screening and treatment could spare 10,490 liver transplants to HCV-infected patients from 2015 to 2035. An estimated 7321 transplants would accrue to patients with end-stage liver disease without HCV and 3169 transplants to those with uncured HCV, providing approximately 52,700 and 22,800 additional life-years, respectively. CONCLUSIONS: Treatment advances for HCV have the potential to generate considerable spillover benefits to patients awaiting transplants for non-HCV-mediated liver failure. For other diseases in which organ transplants are in short supply, our study provides a novel pathway by which positive spillovers may accrue from treatments that prevent end-stage organ disease.

Value of expanding HCV screening and treatment policies in the United States.

OBJECTIVES: To investigate the value of expanding screening and treatment for hepatitis C virus (HCV) infection in the United States. STUDY DESIGN: Discrete-time Markov model. METHODS: We modeled HCV progression and transmission to analyze the costs and benefits of investment in screening and treatment over a 20-year time horizon. Population-level parameters were estimated using National Health and Nutrition Examination Survey data and published literature. We considered 3 screening scenarios that vary in terms of clinical guidelines and physician awareness of guidelines. For each screening scenario, we modeled 3 approaches to treatment, varying the fibrosis stage of treatment initiation. Net social value was the key model outcome, calculated as the value of benefits from improved quality-adjusted survival and reduced transmission minus screening, treatment, and medical costs. RESULTS: Expanded screening policies generated the largest value to society. However, this value is constrained by the availability of treatment to diagnosed patients. Screening all individuals in the population generates $0.68 billion in social value if diagnosed patients are treated in fibrosis stages F3-F4 compared with $824 billion if all diagnosed patients in stages F0-F4 are treated. Moreover, increased screening generates cumulative net social value by year 8 to 9 under expanded treatment policies compared with 20 years if only patients in stages F3-F4 are treated. CONCLUSIONS: Although increasing screening for HCV may generate some value to society, only when paired with expanded access to treatment at earlier disease stages will it produce considerable value. Such a "test and treat" strategy is likely to entail higher short-term costs but also yield the greatest social benefits.

Costs and spillover effects of private insurers' coverage of hepatitis C treatment.

OBJECTIVES: Hepatitis C virus (HCV) treatment incentives for private payers may be misaligned because payers must bear immediate costs and may not realize long-term benefits. However, these benefits may accrue to future payers, including Medicare. We examined how and to what extent private payers' current HCV treatment coverage decisions impact Medicare's and private payers' future costs. STUDY DESIGN: Discrete-time Markov model. METHODS: We modeled HCV disease progression and transmission to simulate the economic and social effects of different private-payer HCV treatment scenarios on Medicare. The model examined differences between a baseline scenario (current practice guidelines) and 2 alternative scenarios that expand treatment coverage. Spillover effects were measured as reduced HCV treatment costs and medical expenditures in Medicare. We calculated the spillover effects and net social value of each scenario (total value of quality-adjusted life-years accrued over time minus cumulative treatment and medical costs). RESULTS: With expanded HCV treatment coverage, private payers experience reduced medical expenditures in the 3-to-5-year time horizon; however, they still face higher treatment costs. Over a 20-year horizon, private payers experience overall savings of $10 billion to $14 billion after treatment costs. The expansion of coverage by private payers generates positive spillover benefits to Medicare of $0.3 billion to $0.7 billion over a 5-year horizon, and $4 billion to $11 billion over a 20-year horizon. CONCLUSIONS: When private payers increase HCV treatment coverage, they may achieve significant savings while inducing spillover benefits to Medicare. Future savings, however, may not motivate immediate treatment investments among private payers who experience high beneficiary turnover.

Cost-Effectiveness of Genotype 1 Chronic Hepatitis C Virus Treatments in Patients Coinfected with Human Immunodeficiency Virus in the United States.

INTRODUCTION: New treatments for chronic hepatitis C virus (HCV) are highly effective in patients coinfected with human immunodeficiency virus (HIV). This study estimated the cost-effectiveness of treatments for genotype 1 (GT1) HCV in HIV-coinfected patients. METHODS: A Markov model based on HCV natural history was used. The base-case analysis included both treatment-naïve and -experienced patients. Alternatives were ombitasvir/paritaprevir/ritonavir, dasabuvir with or without ribavirin (3D ± R) for 12 or 24 weeks, sofosbuvir plus peginterferon and R (SOF + PR) for 12 weeks, SOF + R for 24 weeks, and no treatment (NT). A subgroup analysis restricted to treatment-naïve, non-cirrhotic patients compared 3D ± R for 12 weeks to SOF plus ledipasvir (LDV) for 12 weeks and NT. Transition probabilities, utilities, and costs were obtained from the published literature. Outcomes were measured over a lifetime horizon and included rates of compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma and liver-related death, total costs, life-years, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). RESULTS: In the base-case, SOF + R was dominated by both SOF + PR and 3D ± R. Compared to SOF + PR, 3D ± R had an ICER of $45,581. The lifetime rates of liver morbidity and mortality were lower among those treated with 3D ± R compared to SOF + PR, SOF + R, or NT. In the subgroup analysis, 3D ± R was cost-effective compared to NT at a threshold of $50,000 per QALY (ICER $27,496). SOF/LDV had an ICER of $104,489 per QALY gained compared to 3D ± R. CONCLUSION: In the GT1 HCV population coinfected with HIV, 3D ± R was cost-effective compared to NT, SOF + R, and SOF + PR. In the treatment-naïve sub-population, 3D ± R was cost-effective compared to NT and SOF/LDV.

Cost-effectiveness of Ombitasvir/Paritaprevir/Ritonavir, Dasabuvir+Ribavirin for US Post-Liver Transplant Recurrent Genotype 1 HCV.

BACKGROUND & AIMS: Orthotopic liver transplant patients with recurrent hepatitis C (HCV) historically have had limited treatment options. Ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin (3D+R) was approved by the FDA in December 2014 for liver transplant recipients with recurrent genotype 1 HCV, in whom it is effective and well-tolerated. METHODS: Using a two-phase Markov model, we analysed the cost-effectiveness of 3D+R in liver transplant recipients, the only HCV treatment with FDA approval in this population. As a sensitivity analysis, we also considered the cost-effectiveness of pegylated interferon plus ribavirin, the only other therapy with data from Phase III trials in this population. Patients were given one of three options: 3D+R for 24 weeks, pegylated interferon and ribavirin for 48 weeks (PR48) or no treatment (NT). Patients were then followed through subsequent disease progression until death. Outcome measures analysed were: lifetime risks of liver morbidity and mortality, treatment costs, non-treatment medical expenditures, and quality-adjusted life years. RESULTS: Treatment with 3D+R was associated with a significantly lower lifetime risk of liver-related morbidity and mortality than treatment with PR48 or NT. 3D+R also was associated with a higher gain in quality-adjusted life years (11.3 compared to 8.25 with NT) and lower discounted overall costs ($423,585 compared to $724,757 with NT). CONCLUSIONS: The use of 3D+R for liver transplant recipients with recurrent HCV is an outcome-improving and cost-effective regimen for this population with limited treatment options and large unmet need.

The Impact of State AIDS Drug Assistance Policies on Clinical and Economic Outcomes of People With HIV.

We investigated the effect of changes to state AIDS Drug Assistance Programs (ADAP) policies, which govern access to antiretroviral therapy (ART), on clinical and economic outcomes among low-income people living with HIV/AIDS. Retrospective analyses of ART access were conducted on state ADAP policies, using data from ADAP Monitoring Reports and Kaiser Family Foundation from 2006 to 2010. We found stricter eligibility requirements reduce the number of HIV-positive individuals with ART access through ADAP, and decreased ART use increases mortality by 2.67 quality-adjusted life years (QALYs) per beneficiary. If the ADAP income eligibility cutoff were decreased by 50 percentage points in each state, 4,626 individuals would lose ART access nationwide. Based on a $22,143 cost/QALY, this policy would save $274 million in health care expenditures (2012 dollars), but result in 12,352 QALYs lost, valued at $1.2 billion. Therefore, states should exercise caution in restricting programs that increase ART access for low-income people living with HIV/AIDS.

Systematic Literature Review and Meta-Analysis of Renal Function in Human Immunodeficiency Virus (HIV)-Infected Patients Treated with Atazanavir (ATV)-Based Regimens.

Some HIV antiretroviral therapies (ART) have been associated with renal toxicities, which become of increasing concern as HIV-infected patients age and develop comorbidities. The objective of this study was to evaluate the relative impact of atazanavir (ATV)-based regimens on the renal function of adult patients with HIV. We conducted a systematic literature review by searching PubMed, EMBASE, Cochrane library, and the CRD from 2000 until March 2013. Major HIV-related conferences occurring in the past two years were also searched. All randomized clinical trials and large cohort studies assessing renal function in treatment-naïve and/or treatment-experienced HIV patients on ATV-based regimens were included. Fixed-effect mixed-treatment network analyses were carried out on the most frequently reported renal outcomes. 23 studies met the inclusion criteria, and change in estimated glomerular filtration rate (eGFR) from baseline to 48 weeks was identified as the main outcome. Two networks including, respectively, six studies (using the Cockcroft-Gault method) and four studies (using MDRD and CKD-EPI) were analysed. With CG network, ATV/r + TDF/FTC was associated with lower impact on the decline of eGFR than ATV/cobicistat + TDF/FTC but with higher decrease in eGFR than ATV/r + ABC/3TC (difference in mean change from baseline in eGFR respectively +3.67 and -3.89). The use of ATV/cobicistat + TDF/FTC led to a similar decline in eGFR as EVG/cobicistat/TDF/FTC. With respect to third agents combined with TDF/FTC, ATV/r had a lower increase in eGFR in comparison to EFV, and no difference was shown when compared to SQV/r and DRV/r. The effect of ATV-based regimens on renal function at 48 weeks appears similar to other ART regimens and appears to be modest regardless of boosting agent or backbone, although TDF containing backbones consistently leads to greater decline in eGFR.

Comparative value of four measures of retention in expert care in predicting clinical outcomes and health care utilization in HIV patients.

This study compared the ability of four measures of patient retention in HIV expert care to predict clinical outcomes. This retrospective study examined Veterans Health Administration (VHA) beneficiaries with HIV (ICD-9-CM codes 042 or V08) receiving expert care (defined as HIV-1 RNA viral load and CD4 cell count tests occurring within one week of each other) at VHA facilities from October 1, 2006, to September 30, 2008. Patients were ≥18 years old and continuous VHA users for at least 24 months after entry into expert care. Retention measures included: Annual Appointments (≥2 appointments annually at least 60 days apart), Missed Appointments (missed ≥25% of appointments), Infrequent Appointments (>6 months without an appointment), and Missed or Infrequent Appointments (missed ≥25% of appointments or >6 months without an appointment). Multivariable nominal logistic regression models were used to determine associations between retention measures and outcomes. Overall, 8,845 patients met study criteria. At baseline, 64% of patients were virologically suppressed and 37% had a CD4 cell count >500 cells/mm3. At 24 months, 82% were virologically suppressed and 46% had a CD4 cell count >500 cells/mm3. During follow-up, 13% progressed to AIDS, 48% visited the emergency department (ED), 28% were hospitalized, and 0.3% died. All four retention measures were associated with virologic suppression and antiretroviral therapy initiation at 24 months follow-up. Annual Appointments correlated positively with CD4 cell count >500 cells/mm3. Missed Appointments was predictive of all primary and secondary outcomes, including CD4 cell count ≤500 cells/mm3, progression to AIDS, ED visit, and hospitalization. Missed Appointments was the only measure to predict all primary and secondary outcomes. This finding could be useful to health care providers and public health organizations as they seek ways to optimize the health of HIV patients.