Use of Direct-Acting Antiviral Agents and Survival Among Medicare Beneficiaries with Dementia and Chronic Hepatitis C.
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ABSTRACT: Background
Many patients with Alzheimer's disease and related dementia (ADRD) have chronic hepatitis C due to the high prevalence of both conditions among elderly populations. Direct-acting antivirals (DAAs) are effective in treating hepatitis C virus (HCV). However, the complexity of ADRD care may affect DAA use and outcomes among patients with HCV and ADRD. Little information exists on uptake of DAAs, factors associated with DAA use, and health benefits of DAAs among patients with HCV and ADRD.Objective
To examine use and survival benefits of DAAs in Medicare patients with HCV and ADRD.Methods
The study included Medicare patients with HCV between 2014 and 2017. We estimated Cox proportional hazards regressions to examine the association between having ADRD and DAA use, and the relation between DAA use and survival among patients with HCV and ADRD.Results
The adjusted hazard of initiating a DAA was 50% lower in patients with ADRD than those without ADRD (adjusted HR?=?0.50, 95% CI: 0.46-0.54). The hazard of DAA use among ADRD patients with behavioral disturbances was 68% lower than non-ADRD patients (adjusted HR?=?0.32, 95% CI: 0.28-0.37). DAA treatment was associated with a significant reduction in mortality among ADRD patients (adjusted HR?=?0.52, 95% CI: 0.44-0.61).Conclusion
The rate of DAA treatment in patients with HCV and ADRD was low, particularly among those with behavioral disturbance. The survival benefits of DAA treatment for patients with ADRD were substantial.
SUBMITTER: Tran L
PROVIDER: S-EPMC7855832 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
Publications
Use of Direct-Acting Antiviral Agents and Survival Among Medicare Beneficiaries with Dementia and Chronic Hepatitis C.
Tran Linh L Jung Jeah J Carlin Caroline C Lee Sunmin S Zhao Chen C Feldman Roger R
Journal of Alzheimer's disease : JAD 20210101 1
<h4>Background</h4>Many patients with Alzheimer's disease and related dementia (ADRD) have chronic hepatitis C due to the high prevalence of both conditions among elderly populations. Direct-acting antivirals (DAAs) are effective in treating hepatitis C virus (HCV). However, the complexity of ADRD care may affect DAA use and outcomes among patients with HCV and ADRD. Little information exists on uptake of DAAs, factors associated with DAA use, and health benefits of DAAs among patients with HCV ...[more]
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Project description:Importance: Direct-acting antiviral (DAA) drugs are highly effective in curing hepatitis C virus (HCV) infection. Previous simulations showed extended life as a key health advantage of DAA drugs, but real-world evidence on the association between DAA treatment and reduced mortality is limited.Objectives: To examine the association of DAA treatment with mortality among Medicare beneficiaries with hepatitis C.Design, setting, and participants: This cohort study used Medicare claims data of beneficiaries who sought hepatitis C care for the first time between January 1, 2014, and December 31, 2016, after at least a 1-year washout period. Medicare Part D files were used in identifying DAA therapy initiation and completion. Death dates, demographic data, and indicators of health risks were obtained from the Master Beneficiary Summary Files. Beneficiaries with hepatitis C were considered as patients with DAA treatment if they initiated DAA therapy during the study period. Beneficiaries with hepatitis C who did not initiate DAA therapy during the study period were considered as patients without DAA treatment. Patients without DAA treatment were selected using 1-to-1 propensity score matching. Data were analyzed between September 1, 2019, and March 31, 2020.Exposures: Completion of DAA treatment.Main outcomes and measures: Time to death from the index date of seeking hepatitis C care after at least a 1-year washout period. Cox proportional hazards regression models with time-varying exposure were used to compare mortality rates between propensity score-matched cohorts of patients with DAA treatment and those without DAA treatment. Separate analyses were performed for patients with or without cirrhosis. Heterogeneity in the association between DAA treatment and mortality by sex and dual-eligibility status was examined.Results: A propensity score-matched sample of 51?478 Medicare beneficiaries with a mean (SD) age of 59.4 (11.1) years and 30 473 men (59.2%) was assessed. Of this total, 8240 patients (16.0%) had cirrhosis (5224 men [63.4%]; mean [SD] age, 62.3 [9.7] years) and 43?238 patients (84.0%) had no cirrhosis (25 249 men [58.4%]; mean [SD] age, 58.8 [11.3] years). The adjusted hazard ratio (HR) of dying between patients with DAA treatment and those without DAA treatment in the cirrhosis group was 0.51 (95% CI, 0.46-0.57). The association of DAA treatment with mortality did not differ by sex (women vs men: HR, 0.46 [95% CI, 0.38-0.56] vs HR, 0.53 [95% CI, 0.47-0.60]; P?=?.27) or dual-eligibility status (non-dual-eligible HR, 0.52 [95% CI, 0.43-0.63] vs dual-eligible HR, 0.50 [95% CI, 0.44-0.57]; P?=?.80) in the cirrhosis group. The adjusted HR of dying between patients with DAA treatment and those without DAA treatment among patients without cirrhosis was 0.54 (95% CI, 0.50-0.58). The association of DAA treatment with mortality did not differ by sex (women vs men: HR, 0.53 [95% CI, 0.46-0.60] vs HR, 0.55 [95% CI, 0.50-0.60]; P?=?.66) among patients without cirrhosis. However, the survival advantage associated with DAAs for non-dual-eligible beneficiaries was statistically significantly higher than for dual-eligible beneficiaries among patients without cirrhosis (HR, 0.47 [95% CI, 0.41-0.55] vs HR, 0.57 [95% CI, 0.52-0.62]; P?=?.02).Conclusions and relevance: In this cohort study, DAA treatment appeared to be associated with a decrease in mortality among Medicare beneficiaries with or without cirrhosis. These findings suggest that increasing access to DAA drugs for all patients with HCV infection, regardless of disease progression, could improve population health.
| S-EPMC7737657 | biostudies-literature
Project description:ImportanceDirect-acting antiviral (DAA) therapy for hepatitis C is highly effective but expensive. Evidence is scarce on whether DAA therapy reduces downstream medical costs.ObjectiveTo examine the association of DAA therapy with posttreatment medical costs among Medicare beneficiaries.Design, setting, and participantsThis retrospective cohort study obtained data from various Medicare claims files for 2013 to 2017. The study population comprised patients with a hepatitis C diagnosis in 2014 who were enrolled in fee-for-service Medicare and Part D. Multivariate regression models were used to compare changes in medical costs over a 30-month posttreatment follow-up period between patients who used DAA therapy (treatment group) and a propensity score-matched cohort of patients who did not use DAA (control group). The model was estimated separately for patients with and those without cirrhosis. Data were analyzed between September 1, 2019, and March 31, 2020.ExposuresCompletion of DAA therapy.Main outcomes and measuresTwo outcomes were established: hepatitis C or liver disease-related costs and total medical costs. Costs were measured by Medicare-allowed payments, which included Medicare reimbursements, patient responsibilities, and third-party payments.ResultsA propensity score-matched cohort of 15 198 patients (9038 men [59.5%]; mean [SD] age, 60.2 [10.8] years) was analyzed. During the first 6 months after DAA therapy, hepatitis C or liver disease-related costs decreased by $2498 (95% CI, -$3356 to -$1640) in patients with cirrhosis and by $486 (95% CI, -$603 to -$369) in patients without cirrhosis compared with control or untreated patients. Cumulative reductions in hepatitis C or liver disease-related costs during 30 months after DAA treatment were $15 808 (95% CI, -$22 530 to -$9085) in patients with cirrhosis and $5372 (95% CI, -$6384 to -$4360) in patients without cirrhosis. Among those who used DAA therapy compared with control patients, total medical costs decreased by $2905 (95% CI, -$4832 to -$979) in patients with cirrhosis and by $1287 (95% CI, -$2393 to -$283) in patients without cirrhosis during the first 6 months after DAA therapy. No statistically significant association was found between DAA therapy and total medical cost reductions after 12 months of follow-up. Cumulative reductions in total costs during 30 months after DAA therapy were $7074 (95% CI, -$18 448 to $4298) in patients with cirrhosis and $7497 (95% CI, -$14 287 to -$709) in patients without cirrhosis.Conclusions and relevanceThis study reported that DAA therapy appeared to be associated with a decrease in hepatitis C or liver disease-related costs for 30 months after treatment and with reduction in total medical costs for only 12 months after treatment in patients with or without cirrhosis. Longer-term follow-up studies with diverse outcomes are necessary to assess the value of DAA therapy.
| S-EPMC7327546 | biostudies-literature
Project description:Medicaid prior authorization (PA) policies for treatment of hepatitis C virus (HCV) with direct-acting antiviral (DAA) therapy are changing. We aimed to evaluate effects of changes in PA requirements on treatment uptake and to determine the factors associated with DAA treatment among Florida Medicaid beneficiaries with HCV. This is a retrospective cohort analysis of Florida's Medicaid administrative claims and electronic medical records (2013-2018). A total of 14,063 newly diagnosed patients with HCV were grouped based on human immunodeficiency virus (HIV) co-infection and/or a substance use disorder (SUD) (7,735 HCV mono-infected with a SUD, 5,180 HCV mono-infected without a SUD, 564 HCV/HIV co-infected with a SUD, and 584 HCV/HIV co-infected without a SUD). Although the treatment rate increased three-fold after June 1, 2016, when a fibrosis-stage restriction was eliminated, only 8% received DAAs. Compared to HCV mono-infected without a SUD, HCV mono-infected with a SUD and HCV/HIV co-infected with a SUD were 47% (adjusted hazard ratio, 0.53; 95% confidence interval, 0.47-0.60) and 59% (adjusted hazard ratio, 0.41; 95% confidence interval, 0.28-0.61) less likely to initiate DAAs. Those with HCV/HIV/SUD did not experience a DAA initiation increase after a fibrosis-stage restriction was eliminated. Compared with Whites, Blacks were less likely to receive DAAs but were more likely to complete treatment. Use of medication-assisted therapy was low, despite those on medication-assisted therapy being 60% more likely to initiate DAA therapy and no more likely to discontinue therapy. Conclusion: Despite changes in Florida's Medicaid PA requirements for DAA treatment, only 8% received treatment. Disparities in treatment access were found among patients with HIV and a SUD, and who were Black.
| S-EPMC7850300 | biostudies-literature
Project description:Several direct-acting antiviral agents (DAAs) have marketing authorization in Europe and in the USA and have changed the landscape of hepatitis C treatment: each DAA has its own metabolism and drug-drug interactions (DDIs), and managing them is a challenge. To compile the pharmacokinetics and DDI data of the new DAA and to provide a guide for management of DDI. An indexed MEDLINE search was conducted using the keywords: DAA, hepatitis C, simeprevir, daclatasvir, ledipasvir, sofosbuvir, 3D regimen (paritaprevir/ritonavir, ombitasvir, dasabuvir), DDI and pharmacokinetics. Data were also collected from hepatology, and infectious disease and clinical pharmacology conferences abstracts. Food can play a role in the absorption of DAAs. Most of the interactions are linked to metabolism (cytochrome P450-3 A4 [CYP3A4]) or hepatic and/or intestinal transporters (organic anion-transporting polypeptide and P-glycoprotein [P-gp]). To a lesser extent other pathways can be involved such as breast cancer resistance protein transporter or UDP-glucuronosyltransferase metabolism. DDI are more likely to occur with 3D regimen, daclatasvir, simeprevir and ledipasvir, as they are all both substrates and inhibitors of P-gp and/or CYP3A4, than with sofosbuvir. They can increase concentrations of coadministered drugs and their concentrations may be influenced by P-gp or CYP3A4 inducers or inhibitors. Overdosage or low dosage can be encountered with potent inducers or inhibitors of CYP3A4 or drugs with a narrow therapeutic range. The key to interpret DDI data is a good understanding of the pharmacokinetic profiles of the drugs involved. Their ability to inhibit CYP450-3A4 and transporters (hepatic and/or intestinal) can have significant clinical consequences.
| S-EPMC5237698 | biostudies-other
Project description:ImportanceRecent reports based on the US Food and Drug Administration's voluntary Adverse Events Reporting System raised questions about the safety of direct-acting antivirals (DAAs) for treatment of the hepatitis C virus (HCV).ObjectiveTo assess the rates of adverse events in patients with HCV infection exposed to DAAs compared with those not exposed.Design, setting, and participantsA retrospective cohort study calculated unadjusted adverse event rates for exposed vs unexposed time, using claims and clinical data from 3 health systems between January 1, 2012, and December 31, 2017. Of 82 419 eligible adults, a total of 33 808 who met eligibility criteria (age, 18-88 years; HCV quantitative result or genotype from 2012 or later; continuously enrolled; naive to DAA treatment at baseline) were included. Marginal structural modeling methods were used to adjust time-to-event analyses for characteristics that are associated with both outcomes and probability of treatment.Interventions or exposuresExposure to DAAs compared with no DAA exposure.Main outcomes and measuresDeath, multiple organ failure, liver cancer, hepatic decompensation, acute-on-chronic liver event, acute myocardial infarction, ischemic or hemorrhagic stroke, arrhythmia, acute kidney failure, nonliver cancer, hepatitis B reactivation, hospitalizations, and emergency department visits.ResultsOf the 33 808 patients who met all inclusion criteria, 20 899 (61.8%) were men; mean (SD) age was 57.2 (10.6) years. In unadjusted analyses, DAA exposure was associated with significantly lower rates of death (10.7 vs 33.7 events per 1000 person-years; rate ratio [RR], 0.32, 95% CI, 0.25-0.40). Seven other unadjusted adverse clinical events ratios were below 70% and statistically significant favoring the DAA group: multiple organ failure (RR, 0.56; 95% CI, 0.44-0.72), liver cancer (RR, 0.62; 95% CI, 0.48-0.80), hepatic decompensation (RR, 0.62; 95% CI, 0.52-0.73), acute-on-chronic liver event (RR, 0.68; 95% CI, 0.56-0.84), acute myocardial infarction (RR, 0.64; 95% CI, 0.42-0.97), ischemic stroke (RR, 0.63; 95% CI, 0.42-0.95), and hemorrhagic stroke (RR, 0.47; 95% CI, 0.25-0.89); none favored the non-DAA group. In the marginal structural modeling-adjusted analysis, DAA exposure was associated with statistically significant lower odds of adverse events than non-DAA exposure for death (adjusted odds ratio [aOR], 0.42; 95% CI, 0.30-0.59), multiple organ failure (aOR, 0.67; 95% CI, 0.49-0.90), hepatic decompensation (aOR, 0.61; 95% CI, 0.49-0.76), acute-on-chronic liver event (aOR, 0.71; 95% CI, 0.56-0.91), and arrhythmia (aOR, 0.47; 95% CI, 0.25-0.88).Conclusions and relevanceDirect-acting antiviral exposure may not be associated with higher rates of any serious adverse events, including those related to liver, kidney, and cardiovascular systems. Safety concerns based on previous reports did not appear to be supported in this study with more comprehensive data and rigorous statistical methods.
| S-EPMC6563580 | biostudies-literature
Project description:Abrupt alanine aminotransferase (ALT) elevation during direct-acting antiviral agents (DAA) treatment is an uncommon but noticeable adverse event in chronic hepatitis C (CHC) patients, which may lead to early termination of treatment. This study aims to investigate the incidence, outcome and predictors of the on-treatment ALT elevation during DAA therapy.CHC patients treated with DAA regimen in Chang Gung Memorial Hospital, Linkou branch during March 2015 to March 2019 were recruited. Prospective scheduled ALT assessment at baseline, 2nd, 4th, 8th, and 12th/24th weeks were recorded. Pretherapy host and viral factors were compared between patients with and without on-treatment ALT elevation. Multivariate logistic regression was used for independent factors for on-treatment ALT elevation.A total of 1563 CHC patients treated with grazoprevir/elbasvir, glecaprevir/pibrentasvir and sofosbuvir-based regimen were analyzed. On-treatment ALT elevation occurred in 10.9% patients while those treated with glecaprevir/pibrentasvir had the least possibility (5.4%). Only 1.4% patients had ≥grade 3 ALT elevation events. The presence of such events had no impact on sustained virological response 12 rates. Hepatitis B virus coinfection (aOR: 3.599, P < 0.001) and higher pretherapy ALT (1-5x, ≥5x upper limit of normal: aOR: 2.632, P = 0.024, aOR: 4.702, P = .011, respectively) were significant predictors for ALT elevation.On-treatment ALT elevation occurred in one-tenth CHC patients treated with preferred DAAs but had no impact on sustained virological response rate.
| S-EPMC7489670 | biostudies-literature
Project description:IntroductionThe advent of direct-acting antiviral agents for treating hepatitis C virus infection has made hepatitis C virus elimination possible. Rural patients with hepatitis C virus infection may be less likely to access direct-acting antiviral agents, but the real-world evidence is scarce on urban-rural disparities in direct-acting antiviral agent utilization.MethodsThis retrospective cohort study was conducted in 2019-2020 using Medicare data to examine urban-rural disparities in direct-acting antiviral agent utilization among newly diagnosed patients with hepatitis C virus infection in 2014-2016. Direct-acting antiviral agent use was defined as filling ≥1 prescription for direct-acting antiviral agents during 2014-2017, and patient's urban-rural status was classified on the basis of their ZIP code of residence. This study evaluated the associations between multilevel factors and direct-acting antiviral agent use with a focus on urban-rural disparities. It also assessed changes over time in urban-rural disparities in direct-acting antiviral agent utilization using multivariable cause-specific Cox regression analyses with time-varying hazard ratios.ResultsAmong 204,018 new patients with hepatitis C virus infection, about 30% received direct-acting antiviral agents during 2014-2017. Cumulative direct-acting antiviral agent use gradually increased over time in both urban and rural patients. However, the increase was greater in urban patients than in rural patients. In the first year of follow-up, rural patients had a similar rate of receiving direct-acting antiviral agents (adjusted hazard ratio=1.03, 95% CI=1.00, 1.07), but they were less likely to use direct-acting antiviral agents in later years than urban patients (adjusted hazard ratio=0.85, 95% CI=0.81, 0.90 in the second year, adjusted hazard ratio=0.82, 95% CI=0.76, 0.89 in the third year, and adjusted hazard ratio=0.76, 95% CI=0.64, 0.90 in the fourth year of follow-up).ConclusionsThis study reveals important gaps in hepatitis C virus treatment and suggests increasing urban-rural disparities in direct-acting antiviral agent utilization. Enhancing direct-acting antiviral agent uptake in rural populations with hepatitis C virus infection will help reduce hepatitis C virus‒related health disparities and reach the national goal of eliminating hepatitis C virus infection.
| S-EPMC7855597 | biostudies-literature
Project description:Around 71 million people are chronically infected with HCV worldwide. HCV antiviral drug development has been remarkable. The availability of pangenotypic direct-acting antivirals with excellent efficacy and good tolerability profiles offer a unique opportunity to achieve HCV elimination worldwide. IFN-free DAA combinations can now cure HCV in more than 95% of patients with HCV infection after 8-12 weeks of treatment. Programmes to eliminate HCV must include increased screening (risk-based and universal), linkage to care, as well as increased access to treatment worldwide. In this paper, we will review the available data on recently approved direct-acting antiviral agents, with sustained virological response that reaches almost 100%.
| S-EPMC7713514 | biostudies-literature
Project description:Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies. In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host-targeting entry inhibitors (HTEIs) was highly effective in inhibiting viral dissemination of resistant genotype 2 viruses. Combining HTEIs with DAAs prevented antiviral resistance and led to rapid elimination of the virus in cell culture model. In conclusion, our work provides evidence that cell-cell transmission plays an important role in dissemination and maintenance of resistant variants in cell culture models. Blocking virus cell-cell transmission prevents emergence of drug resistance in persistent viral infection including resistance to HCV DAAs.
| S-EPMC4022730 | biostudies-literature
Project description:UnlabelledHepatitis C virus (HCV) is the most common cause of mixed cryoglobulinemia syndrome (MCS). The efficacy and safety of all-oral direct-acting antiviral (DAA) therapy in HCV-associated MCS (HCV-MCS) is largely unknown. The authors studied case series of patients with HCV-MCS who were treated with sofosbuvir-based regimens and historical controls treated with pegylated interferon and ribavirin in a single health care network. HCV-MCS was defined by circulating cryoglobulin associated with systemic vasculitis symptoms. Renal involvement (n = 7) was established by kidney biopsy (n = 5) or by two or more of the following clinical findings: reduced kidney function, proteinuria, or hematuria with other causes excluded (n = 2). Twelve patients received DAA therapy between December 2013 and September 2014. Median age was 61 years, 58% were male, and 50% had cirrhosis. Median baseline serum creatinine was 0.97 mg/dL (range 0.7-2.47). Four patients received rituximab concurrent with DAA therapy. Sustained virological response rate at 12 weeks (SVR12) was 83% overall. Patients with glomerulonephritis who achieved SVR12 experienced an improvement in serum creatinine and a reduction in proteinuria. Cryoglobulin levels decreased in 89% of patients, with median percent decreasing from 1.5% to 0.5% and completely disappearing in four of nine cases who had cryoglobulins measured after treatment. Serious adverse events were infrequent (17%). In contrast, the historical cohort treated with pegylated interferon and ribavirin experienced only 10% SVR12, with 100% experiencing at least one adverse event and 50% experiencing premature discontinuation due to adverse events.ConclusionSVR12 rates for sofosbuvir-based DAA regimens in HCV-MCS were 83%, significantly higher than historical controls treated with pegylated interferon and ribavirin; patients with glomerulonephritis experienced improvement in renal function, including those not concomitantly treated with immunosuppression.
| S-EPMC4718772 | biostudies-literature