Treatment Discontinuation, Adherence, and Real-World Effectiveness Among Patients Treated with Ledipasvir/Sofosbuvir in the United States.
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ABSTRACT: Introduction
Ledipasvir/sofosbuvir (LDV/SOF) for hepatitis C virus (HCV) treatment provides an oral interferon-free treatment regimen with high rates of sustained virologic response (SVR). This study assessed treatment discontinuation, factors associated with treatment completion, and real-world effectiveness.Methods
Patients with HCV treated with LDV/SOF between October 2014 and June 2015 and enrolled in a large US health plan were identified. Expected treatment duration was calculated based on IDSA/AASLD treatment guidelines and US labels using data for genotype, initial treatment regimen, baseline cirrhosis, and prior treatments. Logistic regression was used to identify factors associated with treatment completion, controlling for patient characteristics.Results
The study included 1483 LDV/SOF patients. Mean age was 59.7 years, most were male (63.9%), had commercial insurance (51.9%), and were treatment-naïve (85.6%). Cirrhosis or end stage liver disease was present in 46.1%. Among patients with an expected 8-week treatment regimen, 49.4% were treated for longer. Most patients (99.8%) with expected 12-week treatment durations were adherent to the expected treatment duration. Treatment-experienced patients [odds ratio (OR) 0.124, p < 0.001] and those on Medicare (OR 0.382, p = 0.039) had lower odds of completing the expected treatment regimen, while males were more likely to complete treatment than females (OR 3.235, p = 0.003). SVR12 in patients treated with LDV/SOF was 89.4% (n = 76/85).Conclusion
Half of patients eligible for an 8-week treatment regimen with LDV/SOF were treated longer, while most patients with a 12-week regimen were adherent to the expected treatment duration. Prior HCV treatment, female gender, and Medicare Advantage insurance were associated with lower odds of treatment completion. Overall SVR12 was 89.4%.Funding
Merck & Co. Inc.
SUBMITTER: Puenpatom A
PROVIDER: S-EPMC5595777 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Newer direct-acting antiviral therapies are increasingly becoming the therapy of choice in patients with hepatitis C virus (HCV) infection. Here, we report the safety and effectiveness of sofosbuvir/velpatasvir (SOF/VEL) and ledipasvir/sofosbuvir (LDV/SOF) in real-world cohorts in Germany. METHODS:Patients initiated on SOF/VEL 12 weeks or LDV/SOF 8, 12 or 24 weeks regimens in a single German centre were included in this study. Data on treatment outcomes and adverse events (AE) were analysed in patients with available sustained virologic response 12 weeks after cessation of treatment (SVR12) information overall and by subgroups. RESULTS:This study included 115 patients who received SOF/VEL from July-2016 to July-2017, and 249 patients who received LDV/SOF from November-2014 to September-2015. Overall, SVR12 was achieved in 99% of patients on SOF/VEL ± ribavirin 12 weeks independent of HCV genotype, treatment history, or cirrhosis status, and in 96% of patients treated with LDV/SOF 8 weeks or LDV/SOF ± ribavirin 12 or 24 weeks. In genotype 1 treatment-naïve, non-cirrhotic patients, ?99% achieved SVR12 across SOF/VEL and LDV/SOF regimens. Likewise, 100% of genotype 3-cirrhotic patients on SOF/VEL ± ribavirin regimens achieved SVR12. Grade 3/4 AE were reported in 13 (5.2%) patients on LDV/SOF and in 1 (<1%) patient on SOF/VEL. CONCLUSION:Overall, SOF/VEL and LDV/SOF achieved high SVR rates in a broad patient population. We showed the effectiveness of SOF/VEL as a pan-genotypic regimen, and regardless of treatment history or cirrhosis status. Use of such therapies improves outcomes and contributes towards the global efforts to eradicate HCV.
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Project description:Sofosbuvir and ledipasvir, which have recently been approved for treatment of chronic hepatitis C virus (HCV) infection, are more efficacious and safer than the old standard of care (oSOC) but are substantially more expensive. Whether and in which patients their improved efficacy justifies their increased cost is unclear.To evaluate the cost-effectiveness and budget impact of sofosbuvir and ledipasvir.Microsimulation model of the natural history of HCV infection.Published literature.Treatment-naive and treatment-experienced HCV population defined on the basis of HCV genotype, age, and fibrosis distribution in the United States.Lifetime.Third-party payer.Simulation of sofosbuvir-ledipasvir compared with the oSOC (interferon-based therapies).Quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and 5-year spending on antiviral drugs.Sofosbuvir-based therapies added 0.56 QALY relative to the oSOC at an ICER of $55 400 per additional QALY. The ICERs ranged from $9700 to $284 300 per QALY depending on the patient's status with respect to treatment history, HCV genotype, and presence of cirrhosis. At a willingness-to-pay threshold of $100 000 per QALY, sofosbuvir-based therapies were cost-effective in 83% of treatment-naive and 81% of treatment-experienced patients. Compared with the oSOC, treating eligible HCV-infected persons in the United States with the new drugs would cost an additional $65 billion in the next 5 years, whereas the resulting cost offsets would be $16 billion.Results were sensitive to drug price, drug efficacy, and quality of life after successful treatment.Data on real-world effectiveness of new antivirals are lacking.Treatment of HCV is cost-effective in most patients, but additional resources and value-based patient prioritization are needed to manage patients with HCV.National Institutes of Health.
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Project description:BACKGROUND:The real-world data for the effectiveness and safety of sofosbuvir/ledipasvir (SOF/LDV) with or without ribavirin (RBV) in patients with hepatitis C virus genotype 1 (HCV-1) infection remain limited in Taiwan. METHODS:A total of 273 chronic HCV-1 patients receiving 8, 12, or 24 weeks of SOF/LDV with or without RBV were enrolled. The sustained virologic response rate at week 12 off-therapy (SVR12) by evaluable population (EP) and per-protocol population (PP) were assessed for effectiveness. The treatment discontinuation rate due to adverse events (AEs) and serious AE rate were assessed for safety. Baseline patient characteristics and on-treatment HCV viral kinetics associated with SVR12 were analyzed. RESULTS:The SVR12 rates by EP and PP analyses were 96.7% (95% confidence interval [CI]: 93.9%-98.3%) and 97.5% (95% CI: 94.8%-98.8%), respectively. The rates of treatment discontinuation due to AE and serious AE were 0.4% and 4.4%, respectively. Seven patients with true virologic failure were relapsers. In 2 patients who were lost-to follow-up, one expired at treatment week 3 due to pneumonia which was considered not related to treatment, and one declined follow-up at off-therapy week 4. The SVR12 rates were comparable in terms of baseline patient characteristics and viral decline at week 4 of treatment. CONCLUSIONS:SOF/LDV with or without RBV for 8-24 weeks is well tolerated and achieves a high SVR12 rate in patients with HCV-1 infection in Taiwan.
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Project description:IntroductionRecent changes in antiretroviral therapies (ARTs) may have affected medication adherence of people living with human immunodeficiency virus-1 (HIV-1). In this study adherence to ART regimens among patients with HIV-1 (PWH) across the US during a recent time period was examined and study findings were stratified by US region and state.MethodsA retrospective observational study using the Symphony Health Solution Integrated Dataverse database was conducted. Patients ≥ 18 years of age who had a diagnosis of HIV-1 (without an HIV-2 diagnosis) and who were treated with ART between July 2017 and September 2018 (first pharmacy record: index date) were selected from the data source. Both patients who had not been previously treated with ART and those who were treatment experienced were included. Patients were required to have ≥ 1 medical/pharmacy record ≥ 12 months after their index date (follow-up period). Patient characteristics were examined during a 12-month pre-index period. During the follow-up, medication adherence, measured as the proportion of days covered (PDC), was examined for all patients and stratified by US region and state.ResultsAmong 206,474 adult PWH treated with ART, mean age was 47.9 years, 73.4% were male, and 30.0% were Caucasian. The most prevalent comorbid conditions were hyperlipidemia (25.1%), depressive disorders (14.8%), and type 2 diabetes (12.1%). During the follow-up period, mean (standard deviation) PDC was 74.1% (25.9%) among PWH across the US [Midwest: 74.4% (25.5%); Northeast: 74.3% (26.1%); South: 73.2% (26.3%); West: 76.4% (24.8%)]. Across all US regions, > 60% of PWH had adherence < 90% and > 40% had adherence < 80%; the West had the highest adherent population.ConclusionsAmong PWH treated with ART across the US, a majority had suboptimal adherence. Implementation of strategies to improve ART adherence, including clinical consideration of ARTs with high genetic barriers to resistance, is needed in the US.
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Project description:Background & aimsVoxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) is highly effective for re-treatment of direct-acting antiviral (DAA)-experienced patients with chronic HCV infection. In the present study, predictors of virologic treatment response were analyzed in an integrative analysis of three large real-world cohorts.MethodsConsecutive patients re-treated with VOX/VEL/SOF after DAA failure were enrolled between 2016 and 2021 in Austria, Belgium, Germany, Italy, Spain and Switzerland.ResultsA total of 746 patients were included: median age was 56 (16-88) years and 77% were male. Most patients were infected with HCV genotype 1 (56%) and 3 (32%). 86% of patients carried resistance-associated substitutions in the NS3, NS5A or NS5B regions. Overall, 95.4% (683/716) of patients achieved a sustained virologic response. Treatment effectiveness was significantly affected by advanced liver disease (p <0.001), hepatocellular carcinoma (p <0.001), higher baseline ALT levels (p = 0.02), HCV genotype 3 (p <0.001), and prior VEL/SOF treatment (p = 0.01). In a multivariate analysis, only HCV genotype 3, hepatocellular carcinoma and cirrhosis turned out to be independent predictors of treatment failure. Resistance-associated substitutions, as well as the presence of rare genotypes, did not impact treatment outcome. The effectiveness of rescue therapy with glecaprevir/pibrentasvir and SOF, with or without ribavirin, for 12 to 24 weeks was found to be high (100%).ConclusionsInfection with HCV genotype 3, the presence of liver cancer and cirrhosis are independently associated with failure of VOX/VEL/SOF re-treatment. It is unclear whether the addition of ribavirin and/or extension of treatment duration may be effective to avoid virologic relapse on VOX/VEL/SOF. However, rescue treatment with glecaprevir/pibrentasvir+SOF seems to be effective.Impact and implicationsRepresentative data on the effectiveness of voxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) in clinical practice are still scarce and the collection of a larger number of patients with difficult-to-treat cofactors including the assessment of resistance-associated substitution profiles is required before more specific recommendations for optimal re-treatment in these patients can be given. Thus, we aimed to analyze treatment effectiveness and predictors of virologic response to VOX/VEL/SOF in an integrative analysis of three large real-word cohorts. The study results, derived from a multicenter cohort consisting of 746 patients, demonstrated that re-treatment with VOX/VEL/SOF is an effective salvage therapy associated with an overall per protocol sustained virologic response rate of 95%. Hepatocellular carcinoma onset, cirrhosis and HCV genotype 3 were identified as independent negative predictors of treatment response, whereas resistance-associated substitutions, as well as rare genotypes and chimera, did not impact sustained virologic response rates following re-treatment with VOX/VEL/SOF.
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Project description:This study demonstrates real-world effectiveness of teriparatide in reducing the risk of hip and other fragility fractures. Fracture incidence significantly decreased as adherence and persistence increased for any clinical, vertebral, nonvertebral, and hip fractures among patients who were observed for 2 years after teriparatide initiation.IntroductionExamine the relationship of treatment adherence and persistence to teriparatide with hip and other fractures.MethodsTruven MarketScan Research Databases, 2004 through 2014, provided teriparatide users ?18 years old with continuous coverage 12 months pre- and 24 months post-teriparatide prescription. Adherence (medication possession ratio, MPR) groups were defined as high (?0.80), medium (0.50 ? MPR < 0.80), and low (<0.50). Persistence, allowing for ?90-day gaps between prescriptions, was defined as 1-6, 7-12, 13-18, and 19-24 months. Fracture incidence was summarized and compared by using ANOVA and logistic regression models; the effects of adherence were examined with Cox proportional hazard models with time-dependent covariates for teriparatide exposure.ResultsAmong 14,284 teriparatide subjects, mean age was 68.4 years, 89.8% were female, and 29.6% had a fracture in the previous year; these characteristics were similar across MPR and persistence groups. The effects of adherence and persistence to teriparatide were statistically significant (P < .001) for all fracture types except wrist (P ? .125). By logistic regression, high vs low adherence was associated with reduced risk for any (OR = 0.67; P < .001); vertebral (OR = 0.64; P < .001); nonvertebral (OR = 0.71; P < .001); and hip fractures (OR = 0.52; P < .001) and longer (19-24 months) vs shorter persistence (1-6 months) was associated with reduced risk for any (OR = 0.63, P < .001); vertebral (OR = 0.56, P < .001); nonvertebral (OR = 0.69, P < .001); and hip fractures (OR = 0.48, P < .001). Cox models revealed a significantly reduced risk between high and low adherence for any (OR = 0.69, P < .001); vertebral (OR = 0.60, P < .001); nonvertebral (OR = 0.77, P < .001); and hip fractures (OR = 0.55, P < .001).ConclusionFracture incidence significantly decreased as persistence and adherence to teriparatide increased.
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Project description:Background:Outcomes for patients with metastatic bladder cancer (mBC) are generally poor and progressively worse following first-line (1L) chemotherapy. Objective:To evaluate treatment patterns, survival outcomes, and characteristics of a large, real-world US population of elderly patients with advanced mBC receiving 1L and second-line (2L) treatment retrospectively. Methods:We identified patients with advanced mBC (aged ?66 years)-newly diagnosed between January 1, 2004, and December 31, 2011-in the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program-Medicare linked database and assessed their palliative systemic chemotherapy treatments and survival outcomes. Results:Of 1703 eligible patients, 42% received 1L chemotherapy; 1L-treated patients tended to be younger and healthier than nontreated patients. Only 27% of 1L-treated patients received cisplatin-based chemotherapy, most commonly cisplatin-gemcitabine. Cisplatin-treated patients were younger and had fewer comorbidities than non-cisplatin-treated patients. Thirty-five percent of 1L-treated patients subsequently received 2L chemotherapy. Patients received a variety of 2L agents as combination chemotherapy (52%) or single-agent chemotherapy (39%). Median overall survival durations in 1L-treated and 2L-treated patients were 8.5 and 7.9 months, respectively. Conclusions:Results from this retrospective SEER-Medicare database analysis underscore the historical inadequacies of 1L and 2L treatments in elderly patients with advanced mBC. Few patients were treated with 1L chemotherapy, a minority of whom received 1L cisplatin-based chemotherapy, and even fewer received 2L chemotherapy. These findings highlight the disconnect between 1L treatment in clinical trials and treatment in the real-world setting and the lack of standard approaches to 2L treatment in the United States.
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