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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Adherence to chronic hepatitis B treatment guideline recommendations for laboratory monitoring of patients who are not receiving antiviral treatment.

BACKGROUND: Hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) levels predict future complications in chronic hepatitis B (CHB) patients. To determine when to initiate antiviral therapy, treatment guidelines recommend monitoring of HBV DNA and ALT levels at least annually. This study aimed to assess adherence to treatment guideline-recommended monitoring of CHB patients not receiving antiviral treatment and to identify predictors of laboratory monitoring and subsequent initiation of antiviral therapy. METHODS: This retrospective cohort study used data from a large US health care claims database over a 5-year period (January 1, 2003 to December 31, 2007). The study population included patients 18-65 years of age with at least two paid medical claims with an ICD-9 code for CHB, at least one positive hepatitis B surface antigen test, and at least 12 months of continuous health plan enrollment after initial diagnosis. Descriptive statistics assessed the proportion of patients with claims for ALT and/or HBV DNA monitoring. Multivariate logistic regression models were used to determine predictors of monitoring and subsequent antiviral therapy. RESULTS: The study included 1,168 CHB patients, with a mean follow-up of 728 days (median = 696 days). The proportion monitored at least every 12 months was 53.3% for ALT, 39.0% for HBV DNA, and 35.1% for both. Significant predictors of monitoring were a higher Deyo-Charlson Comorbidity Index (DCCI) score for ALT (OR 1.90, p < 0.001), male gender for HBV DNA (OR 1.49, p < 0.01), and a higher DCCI score (OR 1.10, p < 0.05) and male gender (1.46, p < 0.01) for both. Significant predictors of subsequent initiation of antiviral treatment were HBV DNA monitoring (OR 2.08, p < 0.001), a higher DCCI score (OR 1.24, p < 0.001), and male gender (OR 1.53, p < 0.01). CONCLUSIONS: Laboratory monitoring of CHB patients not receiving antiviral treatment is below guideline recommendations, suggesting that initiation of antiviral therapy may also be delayed, leaving patients at risk for disease progression.

Factors associated with complete adherence to HIV combination antiretroviral therapy.

PURPOSE: To assess factors associated with adherence, particularly pill burden, to combination antiretroviral therapy (cART) using multivariate models. METHOD: A cross-sectional survey of US adults with a self-reported diagnosis of HIV/AIDS was conducted between April and May 2007. Respondents on a cART regimen of at least 2 nucleoside reverse transcriptase inhibitors plus at least 1 protease inhibitor or non-nucleoside reverse transcriptase inhibitor (n = 461) were included in the analytic sample. Multiple logistic regression models determined independent predictors of complete adherence (defined as never missing or skipping an antiretroviral dose). RESULTS: Fifty-four percent of respondents reported complete adherence to cART. Adherent respondents reported a lower percentage of hospitalizations (11% vs 28%; P < .0001) and emergency room visits (26% vs 34%; P < .09). Respondents taking the single tablet efavirenz/emtricitabine/tenofovir fixed-dose regimen were significantly more likely to have complete adherence than respondents taking other cART regimens (odds ratio [OR] 2.1, P < .05), and higher imputed daily HIV pill count was associated with lower likelihood of complete adherence (OR 0.93, P < .05). CONCLUSION: This study shows the negative impact of higher pill burden on medication adherence, an important factor associated with treatment outcomes in patients with HIV/AIDS.

A retrospective study of HIV antiretroviral treatment persistence in a commercially insured population in the United States.

This study examined factors associated with persistence (time from initiation to discontinuation of treatment) on initial antiretroviral (ARV) therapy in commercially insured HIV patients in the United States, a population not well researched. This retrospective analysis of US health insurance claims data from 1 January 2003 to 30 June 2008 included treatment-naive patients aged 18-65 years with an HIV diagnosis receiving ARV therapy consisting of at least two individual nucleoside reverse transcriptase inhibitors (NRTIs) or one fixed-dose combination NRTI, plus at least one nonnucleoside reverse transcriptase inhibitor (NNRTI) or one protease inhibitor (PI), with or without ritonavir. Descriptive statistics, Kaplan-Meier survival estimation, and Cox proportional hazards regression models were completed. Patients were considered persistent until any component of the regimen was modified or there was a gap in treatment >90 days. A total of 2460 patients met full inclusion criteria (1388 NNRTI and 1072 PI). Mean (SD) time to discontinuation for NNRTI- vs PI-based regimens was 370 (346) vs 295 (338) days (p<0.001). Female sex, substance use, low comorbidity score, index year before 2007, geographical region, and taking a lopinavir/ritonavir regimen predicted discontinuation. Relative to NNRTI-based regimens, PI-based regimens demonstrated a greater risk of discontinuation (hazard ratio [HR], 1.32; p<0.001). The fixed-dose efavirenz/emtricitabine/tenofovir combination yielded the lowest risk of discontinuation (HR, 0.39; p<0.001). HIV treatment persistence was longer with NNRTI-based regimens than PI-based regimens. The fixed-dose regimen of once-daily efavirenz/emtricitabine/tenofovir had the lowest risk of discontinuation.

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.

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.

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.

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.

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.