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Introduction: Molnupiravir (MOV) is an oral antiviral for the treatment of individuals with mild-to-moderate COVID-19 and at high risk of progression to severe disease. Our objective was to conduct a systematic literature review (SLR) of evidence on the effectiveness of MOV in reducing the risk of severe COVID-19 outcomes in real-world outpatient settings., Methods: The SLR was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and using pre-determined population, intervention, comparison, outcome, time, and study design inclusion criteria. Eligible studies were published between January 1, 2021, and March 10, 2023, and evaluated the real-world effectiveness of MOV compared to no treatment in reducing the risk of severe COVID-19 outcomes among outpatients ≥ 18 years of age with a laboratory-confirmed diagnosis of SARS-CoV-2 infection., Results: Nine studies from five countries were included in the review. The size of the MOV-treated group ranged from 359 to 7818 individuals. Omicron variants of SARS-CoV-2 were dominant in all study periods. Most studies noted differences in the baseline characteristics of the MOV-treated and untreated control groups, with the treated groups generally being older and with more comorbidities. Eight studies reported that treatment with MOV was associated with a significantly reduced risk of at least one severe COVID-19 outcome in at least one age group, with greater benefits consistently observed among older age groups., Conclusions: In this SLR study, treatment with MOV was effective in reducing the risk of severe outcomes from COVID-19 caused by Omicron variants, especially for older individuals. Differences in the ages and baseline comorbidities of the MOV-treated and control groups may have led to underestimation of the effectiveness of MOV in many observational studies. Real-world studies published to date thus provide additional evidence supporting the continued benefits of MOV in non-hospitalized adults with COVID-19., (© 2024. Merck & Co., Inc., Rahway, NJ, USA and its affiliates.)

Background and Aims: Historical paired liver biopsy studies are likely to underestimate current progression of disease in patients with chronic hepatitis C virus (HCV) infection. We aimed to assess liver disease progression according to the non-invasive Fibrosis-4 (FIB-4) index in patients with chronic HCV and early disease., Methods and Results: Patients diagnosed with chronic HCV and FIB-4 <3.25 from four international liver clinics were included in a retrospective cohort study. Follow-up ended at start of antiviral therapy resulting in sustained virological response, at time of liver transplantation or death. Primary outcome of advanced liver disease was defined as FIB-4 >3.25 during follow-up. Survival analyses were used to assess time to FIB-4 >3.25.In total, 4286 patients were followed for a median of 5.0 (IQR 1.7-9.4) years, during which 41 071 FIB-4 measurements were collected. At baseline, median age was 47 (IQR 39-55) years, 2529 (59.0%) were male, and 2787 (65.0%) patients had a FIB-4 <1.45. Advanced liver disease developed in 821 patients. Overall, 10-year cumulative incidence of advanced disease was 32.1% (95% CI 29.9% to 34.3%). Patients who developed advanced disease showed an exponential FIB-4 increase. Among patients with a presumed date of HCV infection, cumulative incidence of advanced disease increased 7.7-fold from 20 to 40 years as opposed to the first 20 years after HCV infection., Conclusions: The rate of advanced liver disease is high among chronic HCV-infected patients with early disease at time of diagnosis, among whom liver disease progression accelerated over time. These results emphasise the need to overcome any limitations with respect to diagnosing and treating all patients with chronic HCV across the globe., Competing Interests: Competing interests: LK, NSE, CW, SvH, OC, JV and RAdM report no conflict of interest. RM received financial compensation for consultancy from AbbVie. AP is an employee of Merck & Co. RJdK declares that the Erasmus University Medical Center, on behalf of RJdK, received honoraria for consulting/speaking from Gilead, Janssen-Cilag, Bristol-Myers Squibb (BMS), AbbVie, MSD, Roche and Norgine, and received research grants from Gilead, Janssen-Cilag, BMS and Roche. BEH has consulted for and received grant/research support from Intercept Pharmaceuticals. SZ reports consultancies for AbbVie, BMS, Gilead, Janssen and Merck. TV has received grants from Gilead Sciences and BMS; is a consultant for Janssen Pharmaceuticals, Gilead Sciences, AbbVie and BMS; and a sponsored lecturer for W L Gore, Gilead Sciences, BMS and AbbVie. HLAJ has served as consultant for and has received grants from AbbVie, Arbutus, BMS, Enyo, Gilead Sciences, Janssen, Medimmune, Merck, Roche, Vir Biotechnology and Viroclinics. JJF has consulted for Abbott, AbbVie, Gilead, Enanta and Roche; and has received grant/research support from AbbVie, Eiger, Gilead, Janssen and Wako/Fujifilm. AJvdM received financial compensation for lecture activities for Zambon and research funding from Gilead, MSD, AbbVie and Zambon., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Molnupiravir is an orally administered antiviral authorized for COVID-19 treatment in adults at high risk of progression to severe disease. Here, we report secondary and post hoc analyses of participants' self-reported symptoms in the MOVe-OUT trial, which evaluated molnupiravir initiated within 5 days of symptom onset in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed COVID-19., Methods: Eligible participants completed a 15-item symptom diary daily from day 1 (randomization) through day 29, rating symptom severity as "none," "mild," "moderate," or "severe"; loss of smell and loss of taste were rated as "yes" or "no." Time to sustained symptom resolution/improvement was defined as the number of days from randomization to the first of 3 consecutive days of reduced severity, without subsequent relapse. Time to symptom progression was defined as the number of days from randomization to the first of 2 consecutive days of worsening severity. The Kaplan-Meier method was used to estimate event rates at various time points. The Cox proportional hazards model was used to estimate the hazard ratio between molnupiravir and placebo., Results: For most targeted COVID-19 symptoms, sustained resolution/improvement was more likely, and progression was less likely, in the molnupiravir versus placebo group through day 29. When evaluating 5 distinctive symptoms of COVID-19, molnupiravir participants had a shorter median time to first resolution (18 vs 20 d) and first alleviation (13 vs 15 d) of symptoms compared with placebo., Conclusions: Molnupiravir treatment in at-risk, unvaccinated patients resulted in improved clinical outcomes for most participant-reported COVID-19 symptoms compared with placebo. Clinical Trials Registration. ClinicalTrials.gov: NCT04575597., Competing Interests: Potential conflicts of interest. Y. G., A. P., M. G. J., Y. Z., Y. Z., A. W.-D., M. B., A. P., C. D. A., and J. M. N. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA, and may own and/or hold stock options in Merck & Co, Inc, Rahway, NJ, USA. J. D. was an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA, at the time of study conduct and holds stock and/or stock options in Merck & Co, Inc, Rahway, NJ, USA. A. Puenpatom also reports travel support from Merck & Co., Inc., Rahway, NJ, USA. A. W. holds stock and/or stock options in Carbon Health Technologies, Inc, and CurieAI for advisory work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: In people with chronic hepatitis C virus (HCV) infection, viral eradication is associated with improved health-related quality of life (HRQOL)., Objective: To assess changes in HRQOL among participants receiving opioid agonist therapy undergoing treatment for HCV infection., Methods: COSTAR (NCT02251990) was a randomized, double-blind, placebo-controlled study. Adults with HCV infection on opioid agonist therapy received elbasvir (50 mg)/grazoprevir (100 mg) or placebo for 12 weeks. HRQOL was evaluated using the Medical Outcomes Study 36-Item Short Form Health Survey version 2 (SF-36v2) Acute Form. Participants remained blinded until 4 weeks after end of treatment., Results: Overall, 201 participants received elbasvir/grazoprevir and 100 participants received placebo. Treatment difference mean change from baseline scores (elbasvir/grazoprevir minus placebo) indicated an improvement in HRQOL at 4 weeks after end of treatment in participants receiving elbasvir/grazoprevir versus those receiving placebo, driven by declining HRQOL in those receiving placebo and improved HRQOL in certain domains among participants receiving elbasvir/grazoprevir. Notable differences in SF-36v2 scores were evident in the general health (mean treatment difference [MTD], 6.00; 95% CI, 1.37-10.63), vitality (MTD, 6.81; 95% CI, 1.88-11.75), and mental health (MTD, 5.17; 95% CI, 0.52-9.82) domains and in the mental component summary score (mean, 2.83; 95% CI, 0.29-5.37). No notable between-treatment differences were evident at treatment weeks 4 or 12., Conclusion: HRQOL in patients receiving medication for opioid dependence was improved following treatment for HCV infection with elbasvir/grazoprevir, suggesting that eradication of HCV infection with direct-acting antivirals is associated with improved HRQOL., Trial Registration Number: ClinicalTrials.gov, NCT02251990.

Purpose: The evolving epidemiology and treatment landscape of COVID-19 necessitates research into potential drug-drug interactions (pDDIs) from the use of new treatments for COVID-19, particularly those that contain ritonavir, a potent inhibitor of the cytochrome P350 3A4 (CYP3A4) metabolic pathway. In this study, we assessed the prevalence of pDDIs between medications for chronic conditions metabolized through the CYP3A4 metabolic pathway and ritonavir-containing COVID-19 medications in the US general population., Methods: This study combined National Health and Nutrition Examination Survey (NHANES) waves 2015 to 2016 and 2017 to March 2020 to observe pDDI prevalence between ritonavir-containing therapy and coadministered medications among US adults 18 years or older. CYP3A4-mediated medications were identified from affirmative medication questionnaire response and associated prescription examination by surveyors. CYP3A4-mediated medications with associated pDDIs with ritonavir and assessed pDDI severity (minor, major, moderate, and severe) were obtained from the University of Liverpool's COVID-19 online drug interaction checker, Lexicomp, and US Food and Drug Administration fact sheets. pDDI prevalence and severity were evaluated by demographic characteristics and COVID-19 risk factors., Findings: A total of 15,685 adult participants were identified during the 2015 to 2020 NHANES waves. Survey participants used a mean (SD) of 2.7 (1.8) drugs with likelihood of a pDDI. The weighted prevalence of major to contraindicated pDDIs among the US population was 29.3%. Prevalence rates among those 60 years and older, with serious heart conditions, with moderate chronic kidney disease (CKD), with severe CKD, with diabetes, and with HIV were 60.2%, 80.7%, 73.9%, 69.5%, 63.4%, and 68.5%, respectively. Results remained largely unchanged after removal of statins from the list of drugs associated with ritonavir-based pDDIs., Implications: Approximately one-third of the US population would be at risk for a major or contraindicated pDDI should they receive a ritonavir-containing regimen, and this risk increases significantly among individuals 60 years or older and with comorbidities such as serious heart conditions, CKD, diabetes, and HIV. The state of polypharmacy in the US population and the quickly changing COVID-19 landscape indicate significant risk of pDDIs among those requiring treatment with ritonavir-containing COVID-19 medications. Practitioners should take polypharmacy, age, and comorbidity profile into account when prescribing COVID-19 therapies. Alternative treatment regimens should be considered, especially for those of older age and those with risk factors for progression to severe COVID-19., (Copyright © 2023. Published by Elsevier Inc.)

BACKGROUND: Patients with COVID-19 receiving ritonavir-containing therapies are at risk of potential drug-drug interactions (pDDIs) because of ritonavir's effects on cytochrome P450 3A4. OBJECTIVE: To assess the prevalence of pDDIs with ritonavir-containing COVID-19 therapy in adults with COVID-19 using the Optum Clinformatics Data Mart database. METHODS: In this retrospective, observational cohort study, patients with COVID-19 aged 18 years or older prescribed cytochrome P450 3A4-mediated medications with supply days overlapping the date of COVID-19 diagnosis between January 1, 2020, and June 30, 2021, were classified as having pDDIs. pDDI was classified as contraindicated, major, moderate, or mild using established drug interaction resources. Prevalence of pDDIs with ritonavir-containing COVID-19 therapy was estimated for the entire cohort and in patient groups with high risk of severe COVID-19 progression or pDDIs. Actual COVID-19 treatments received by the patients, if any, were not considered. Outcomes were presented descriptively without adjusted comparisons. RESULTS: A total of 718,387 patients with COVID-19 were identified. The age-sex standardized national prevalence of pDDIs of any severity was estimated at 52.2%. Approximately 34.5% were at risk of contraindicated or major pDDIs. Compared with patients without pDDI, patients exposed to pDDIs were older and more likely to be female, reside in long-term care facilities, and have risk factors for progression to severe COVID-19. Higher prevalence of major/contraindicated pDDIs was observed in older patients (76.1%), female patients (65.0%), and patients with multiple morbidities (84.6%). CONCLUSIONS: Study findings demonstrate that more than one-third of patients with COVID-19 were at risk of significant pDDIs if treated with ritonavir-containing COVID-19 therapy and highlight the need to assess all patients with COVID-19 for pDDIs. Ritonavir-based therapies may not be appropriate for certain patient groups, and alternative therapies should be considered. DISCLOSURES: Drs Igho-Osagie, Puenpatom, and Grifasi Williams are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. Dr Song and Ms He are employees of Analysis Group, Inc., and served as paid consultants for Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. Drs Yi and Wang, and Mr Berman, and Ms Gu were employees of Analysis Group, Inc., at the time of study conduct. Financial support for this study was provided by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. The study sponsor was involved in the design and conduct of the study; collection, management, analysis, interpretation of data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Background: In the MOVe-OUT trial, molnupiravir showed a clinically meaningful reduction in the risk for hospitalization or death in adults with mild to moderate COVID-19 and risk factors for progression to severe disease., Objective: To identify other potential clinical benefits of molnupiravir versus placebo., Design: Secondary analysis of the randomized, double-blind, placebo-controlled phase 3 component of MOVe-OUT. (ClinicalTrials.gov: NCT04575597)., Setting: 107 sites globally., Participants: 1433 nonhospitalized adults aged 18 years or older with mild to moderate COVID-19., Intervention: Molnupiravir, 800 mg, or placebo every 12 hours for 5 days., Measurements: Changes from baseline in C-reactive protein (CRP) concentration and oxygen saturation (Spo 2 ), need for respiratory interventions (including invasive mechanical ventilation), and need for medical services in all randomly assigned participants through day 29, and need for respiratory interventions and time to discharge in the subgroup of participants who were hospitalized after randomization., Results: Participants receiving molnupiravir showed faster normalization of CRP and Spo 2 , with improvements observed on day 3 of therapy, compared with placebo. Molnupiravir-treated participants had a decreased need for respiratory interventions versus placebo-treated participants (relative risk reduction [RRR], 34.3% [95% CI, 4.3% to 54.9%]), with similar findings in participants who were hospitalized after randomization (RRR, 21.3% [CI, 0.2% to 38.0%]). Hospitalized participants who received molnupiravir were discharged a median of 3 days before those who received placebo. Acute care visits (7.2% vs. 10.6%; RRR, 32.1% [CI, 4.4% to 51.7%]) and COVID-19-related acute care visits (6.6% vs. 10.0%; RRR, 33.8% [CI, 5.6% to 53.6%]) were less frequent in molnupiravir- versus placebo-treated participants., Limitations: Some analyses were performed post hoc. Longer-term benefits of molnupiravir therapy were not evaluated. Participants were not immunized against SARS-CoV-2., Conclusion: The findings suggest there are additional important clinical benefits of molnupiravir beyond reduction in hospitalization or death., Primary Funding Source: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.

In this prospective observational study, data were collected from 34 rheumatology clinics in Italy in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) who started golimumab (GLM) as a second anti-TNFα drug. The primary objective was to evaluate the effectiveness of GLM after 6 months. Changes in quality of life using the EQ-5D-5L were also assessed. A total of 194 patients aged 53.2 ± 12 years started GLM as a second anti-TNF drug: 39 (20.1%) with RA, 91 (46.9%) with PsA and 64 (32.9%) with axSpA. After 6 months of GLM treatment, 68% of RA patients achieved low disease activity (LDA; DAS28-CRP ≤ 3.2), 31.9% of PsA patients achieved minimal disease activity and 32.5% of axSpA patients achieved LDA (ASDAS-CRP < 2.1). Good/moderate EULAR response was achieved in 61.9% and 73.8% of patients with RA and PsA, respectively, and 16% of axSpA patients achieved a 50% improvement in BASDAI. Across all indications, improvements in disease activity measures and EQ-5D-5L domains were observed over 6 months. The main reasons for GLM interruption were lack/loss of efficacy (7.2%) or adverse events (2%). This study confirms the effectiveness of GLM as a second-line anti-TNF for the treatment of RA, PsA and axSpA in a real-world setting in Italy.

Background: Hepatitis C virus (HCV) infections in the United States have increased in recent years, with the most rapid rise among people who inject drugs (PWIDs). Historically, there have been concerns regarding treatment adherence among PWIDs with HCV infection, leading to undertreatment of this population and increased HCV transmission. Elbasvir (EBR)/grazoprevir (GZR) has demonstrated high rates of virologic cure (sustained virologic response [SVR]) in clinical trials enrolling PWIDs with HCV infection. Objective: To evaluate the real-world effectiveness of EBR/GZR in HCV genotype (GT) 1-infected patients with a diagnosis of opioid use disorder. Methods: A retrospective analysis of electronic medical records from the US Department of Veterans Affairs Corporate Data Warehouse. Adults with chronic HCV GT1 infection, ≥1 prescription for EBR/GZR, and ≥1 clinic visit were included. All patients had ≥1 ICD-9/10 code of opioid use disorder. SVR was the primary outcome. Results: 419 patients were included; 97.1% had a history of any illicit drug use and 40.8% were receiving medication for opioid use disorder (MOUD). SVR was achieved by 96.9% (406/419) of all patients, 97.0% (350/361) of those receiving EBR/GZR for 12 weeks, and 95.3% (163/171) of those receiving MOUD. SVR in patients receiving psychiatric medications ranged from 96.1% (221/230) in those taking antidepressant medications to 98.5% (128/130) in those taking mood stabilizers. Conclusion: In this real-world setting, high rates of virologic cure were achieved in patients with HCV GT1 infection on MOUD receiving EBR/GZR for 12 weeks, including patients with multiple comorbidities and high rate of psychiatric medication use.

Background and Aims: Coronavirus disease 2019 (COVID-19) imposes a substantial and ongoing burden on the US healthcare system and society. Molnupiravir is a new oral antiviral for treating COVID-19 in outpatient settings. This study evaluated the cost-effectiveness profile of molnupiravir versus best supportive care in the treatment of adult patients with mild-to-moderate COVID-19 at risk of progression to severe disease, from a US payer's perspective., Methods: The model was developed using a decision tree for the short-term acute phase of COVID-19 and a Markov state transition model for the long-term post-acute phase. This model compared molnupiravir with best supportive care as consistent with the MOVe-OUT trial. Costs were reported in 2021 US dollars. Transition probabilities were derived from the phase III MOVe-OUT trial and the TriNetX real-world electronic health records database. Costs were derived from the TriNetX database and utility values from a de novo, vignette-based utility study. Deterministic and probabilistic sensitivity analyses (DSA/PSA) were conducted. Primary outcomes included proportion hospitalized, proportion who died overall and by highest healthcare setting at the end of the acute phase, quality-adjusted life-years (QALYs), and incremental costs per QALY gained over a lifetime (100 years) horizon, discounted at 3% annually and assessed at a willingness-to-pay (WTP) threshold of $100,000 per QALY., Results: In this model, the use of molnupiravir led to an increase in QALYs (0.210) and decrease in direct total medical costs (-$895) per patient across a lifetime horizon, compared with best supportive care in COVID-19 outpatients. Molnupiravir was the dominant intervention when compared with best supportive care. Patients treated with molnupiravir were less likely to be hospitalized (6.38% vs. 9.20%) and more likely to remain alive (99.88% vs. 98.71%) during the acute phase. Through DSA, molnupiravir treatment effect of hospitalization reduction was identified to be the most influential parameter, and through PSA, molnupiravir remained dominant in 84% of the total simulations and, overall, 100% cost effective., Conclusion: This analysis suggests that molnupiravir is cost effective compared with best supportive care for the treatment of adult outpatients with COVID-19. However, our study was limited by the unavailability of the most recent information on the rapidly evolving pandemic, including new viral variants, patient populations affected, and changes in standards of care. Further research should explore the impact of vaccination on the cost effectiveness of molnupiravir and other therapies, based on real-world data, to account for these changes, including the impact of vaccination and immunity., (© 2022. The Author(s).)

Objective: A few studies have suggested that patients with inflammatory arthritis (IA) who remain persistent with subcutaneous TNF-α inhibitors (SC-TNFi) incur lower health care costs than patients who discontinue treatment, whereas data on the impact of non-persistence on indirect costs are largely lacking. Furthermore, existing estimates are based on fixed follow-ups, in relation to treatment initiation, and therefore do not measure costs in direct relation to treatment discontinuation. Therefore, by capturing costs in direct relation to treatment discontinuation, this study aimed to estimate direct and indirect costs associated with non-persistence with SC-TNFis in IA., Methods: Adult Swedish biologic-naïve IA patients initiating biologic treatment with a SC-TNFi (adalimumab, etanercept, certolizumab or golimumab) between May 6, 2010, and December 31, 2017, were identified in population-based registers with almost complete coverage. IA was defined as a diagnosis of rheumatic arthritis, ankylosing spondylitis/unspecified spondyloarthritis or psoriatic arthritis. Non-persistent patients were matched on propensity score to patients persistent with treatment by at least an additional 12 months. This enabled comparisons of direct healthcare costs and indirect costs for sick leave and disability pension, respectively, 12 months before and 12 months after treatment discontinuation., Results: A balanced cohort of 486 matched pairs was generated. The total direct and indirect costs were significantly higher among non-persistent patients already during the 12 months before index ($20,802 [18,335-23,429] vs. $16,600 [14,331-18,696]). However, while non-persistent patients increased their total direct and indirect costs, persistent patients significantly decreased the same, further widening the difference in costs during the 12-month period after index date ($22,161 [19,754-24,556] vs. $13,465 [11,415-15,729])., Conclusions: Among biologic-naïve Swedish IA patients treated with SC-TNFis, persistent patients incurred about 40% lower aggregated direct and indirect costs compared to non-persistent patients the year following SC-TNFi discontinuation. This highlights the impact of treatment persistence from an economic viewpoint, adding further aspects to the clinical perspective., (© 2021. The Author(s).)

Introduction: Biologic treatments including subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFis) have greatly improved disease management of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) (collectively inflammatory arthritis, IA). Nevertheless, some patients discontinue their first-line treatment; for them, one option may be a subsequent line of the same treatment class (i.e., cycling). The aim of this study was to assess treatment persistence between first- and second-line therapy in Swedish IA patients cycling on SC-TNFis., Methods: Using data from the Swedish Health Data Registers, adult IA patients filling prescriptions between May 1, 2010, and October 31, 2016, for a SC-TNFi (adalimumab, etanercept, certolizumab and golimumab) were included. Treatment persistence was derived based on information from filled prescriptions and a 60-day grace period. Unadjusted and adjusted marginal Cox proportional hazards models were fitted to estimate the relative risk of discontinuation across treatment lines, using robust sandwich covariance matrix estimates to account for intrapatient dependence (i.e., multiple treatment lines per patient). The analysis was restricted to the first two lines of treatment., Results: Of the eligible patients, 3181 were identified as cyclers. Among these, most were female (68%), and 46%, 28% and 26% were diagnosed with RA, AS and PsA, respectively. Both the unadjusted and adjusted analyses showed that the relative risk of discontinuing SC-TNFi treatment was significantly lower in second compared to first line (hazard ratio; 0.60 [0.57, 0.63] and HR; 0.59 [0.56, 0.62]). This finding was also consistent across IA indications., Conclusions: In this study of patients cycling on SC-TNFis in IA, persistence was greater in second- compared to first-line treatment. The finding was consistent across all IA indications. Hence, patients who discontinue their first-line treatment may still benefit from treatment with an alternative SC-TNFi as a second-line therapy in IA., (© 2021. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Objectives: The causal impact method (CIM) was recently introduced for evaluation of binary interventions using observational time-series data. The CIM is appealing for practical use as it can adjust for temporal trends and account for the potential of unobserved confounding. However, the method was initially developed for applications involving large datasets and hence its potential in small epidemiological studies is still unclear. Further, the effects that measurement error can have on the performance of the CIM have not been studied yet. The objective of this work is to investigate both of these open problems., Methods: Motivated by an existing dataset of HCV surveillance in the UK, we perform simulation experiments to investigate the effect of several characteristics of the data on the performance of the CIM. Further, we quantify the effects of measurement error on the performance of the CIM and extend the method to deal with this problem., Results: We identify multiple characteristics of the data that affect the ability of the CIM to detect an intervention effect including the length of time-series, the variability of the outcome and the degree of correlation between the outcome of the treated unit and the outcomes of controls. We show that measurement error can introduce biases in the estimated intervention effects and heavily reduce the power of the CIM. Using an extended CIM, some of these adverse effects can be mitigated., Conclusions: The CIM can provide satisfactory power in public health interventions. The method may provide misleading results in the presence of measurement error., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Direct-acting antivirals (DAAs) are entering the hepatitis C virus (HCV) treatment landscape in Hong Kong, prompting the need for cost-effectiveness evaluations of these interventions to enable optimal use of healthcare resources., Aims: This study aimed to compare the cost-effectiveness of DAAs to standard-of-care pegylated interferon plus ribavirin (RBV) in treatment-naïve patients without significant liver fibrosis and to compare different DAAs in patients who are treatment-experienced and/or have advanced liver disease., Methods: A Markov model was constructed to evaluate cost-effectiveness over a lifetime time horizon from the payer perspective. The target population was treatment-naïve and treatment-experienced HCV genotype 1 patients, stratified by degree of liver fibrosis. The model consists of 16 health states encompassing METAVIR fibrosis score (F0-F4), treatment success or failure, decompensated cirrhosis, hepatocellular carcinoma, liver transplant, and liver-related death. The proportions of patients achieving sustained virologic response were obtained from clinical trials. Other inputs were obtained from published and local data. The primary outcome was incremental cost-utility ratio for each DAA versus pegylated interferon + ribavirin and among different DAAs., Results: In treatment-naïve F0-2 HCV patients, all DAAs were cost-effective in genotype 1a and daclatasvir + asunaprevir, elbasvir/grazoprevir, ledipasvir/sofosbuvir, and glecaprevir/pibrentasvir were cost-effective compared to pegylated interferon + ribavirin in genotype 1b. In genotypes 1a and 1b, treatment-experienced patients, and F3-4 patients, elbasvir/grazoprevir was the least costly DAA and economically dominant over most other DAAs., Conclusions: DAAs can be a cost-effective option for the treatment of genotype 1 HCV patients in Hong Kong, and elbasvir/grazoprevir is cost-effective.

Objective: To examine real-world treatment persistence, colectomy-free survival and treatment switching patterns in UK patients with ulcerative colitis (UC) prescribed golimumab or adalimumab., Design: This was a retrospective chart review study in adult patients diagnosed with UC using data from 16 National Health Service sites in the UK. Patient records were included in the study if they had initiated first or second-line adalimumab or golimumab between 1 March 2016 and 30 September 2017 (index date). Subjects were required for ≥6 months post treatment initiation. Demographics, clinical characteristics, treatment-related data and colectomy data were extracted over a follow-up period of 6-12 months. Treatment persistence rate was the primary outcome. Colectomy-free survival and treatment switching were secondary outcomes. Outcomes were compared between treatments using χ 2 tests and Fisher's exact test for categorical variables. The t-tests were used for continuous variables. Time-to-event variables were evaluated using Kaplan-Meier curves and log-rank tests., Results: The study included a total of 183 patients (96 (52.5%) prescribed adalimumab; 87 (47.5%) golimumab), and patients were mostly first line (79.8%). Demographic and clinical characteristics were generally similar between treatment groups. Persistence rates within 12 months were 64.6% for adalimumab and 64.4% for golimumab (p=0.681). Overall, 20.2% switched to other therapy within 1 year, with 8.2% golimumab and 12.0% adalimumab switching to another biologic. Of patients prescribed adalimumab, 14.6% had ≥1 dose change, mainly dose escalations. In the 12 months post treatment initiation, 8.2% of patients underwent colectomy, with no significant difference in colectomy-free survival by treatment, p=0.73., Conclusion: This study provides evidence of clinical outcomes and real-world persistence for adalimumab and golimumab in UC. The persistence rates of both therapies were above 64.0% at 12 months following treatment initiation. In addition, the 1-year colectomy-free survival was relatively similar between the two treatments., Competing Interests: Competing interests: Sami Hoque has no conflict of interest. Amy Puenpatom and Christopher Black are employed by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (who funded this study).Simona Boccaletti and Chloe Green were employed by MSD Ltd., UK Jenna Roberts, Ivana Rajkovic and Gary Milligan are employed by Adelphi Real World., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aim: In China, clinical experience with direct-acting antiviral treatments for hepatitis C virus (HCV) infection is still emerging. C-CORAL is a phase 3, multinational, placebo-controlled, double-blind trial of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from the Asia-Pacific region and Russia. Here, we report the data from participants enrolled in China., Methods: Treatment-naive participants with chronic HCV genotype (GT) 1, GT4, or GT6 infection were randomly assigned to receive 50 mg EBR/100 mg GZR for 12 weeks (immediate-treatment group, ITG) or placebo followed by deferred treatment with EBR/GZR (deferred-treatment group, DTG). The primary efficacy end-point was sustained virologic response at 12 weeks after completing treatment (SVR12), and the primary safety end-point was a comparison of safety between participants receiving EBR/GZR and placebo (NCT02251990; Protocol PN-5172-067)., Results: A total of 152 participants in China were randomly assigned (ITG, n = 115; DTG, n = 37). SVR12 was achieved in 96.7% (146/151) participants overall and in 97.3% (142/146) of those with GT1b infection. Four participants relapsed (GT1b, n = 3; GT6a, n = 1). Drug-related AEs were reported in 25 (21.7%) and 9 (24.3%) participants receiving EBR/GZR and placebo, respectively; no drug-related serious adverse events (AEs) occurred. Two (1.7%) participants receiving EBR/GZR had late hepatic transaminase elevations. Patient-reported outcomes indicate improved quality of life at follow-up week 4 in participants receiving EBR/GZR compared to placebo., Conclusion: EBR/GZR administered for 12 weeks represents a highly effective and safe treatment option for Chinese individuals with HCV GT1 infection., (© 2020 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: Real-world treatment of hepatitis C virus (HCV) infection is complicated by many factors that are controlled for in the rigorous clinical trial setting. The aim of the present study was to assess the efficacy of elbasvir/grazoprevir in a Veterans Affairs population with chronic HCV genotype 1b infection., Methods: This was a retrospective analysis of a cohort of patients aged ≥ 18 years with chronic HCV genotype 1b infection and ≥ 1 prescription of elbasvir/grazoprevir between February 1, 2016, and August 31, 2017. The primary analysis was conducted in the per-protocol population, which included all patients who had at least 11 weeks of treatment and had an available assessment for sustained virologic response (SVR) based on virologic data post-follow-up week 4., Results: The per-protocol population included 3371 patients. Overall, 97.3% of patients were male, 60.3% were black, and 85.5% were HCV treatment-experienced. Comorbidities in this population included hypertension (74.4%), history of alcohol use (55.7%), and depression (54.8%). In total, 97.5% of patients (3288/3371) achieved SVR. Among patient sub-groups, SVR was achieved by 96.0% (290/302) of those with chronic kidney disease stage 4/5, 97.8% (1527/1561) of those with a history of drug use, and 96.6% (831/860) of those with cirrhosis. No statistically significant differences were observed in the proportions of patients achieving SVR, regardless of age, race, HCV treatment history, viral load level, treatment regimen/duration, history of drug or alcohol use, HIV co-infection, or chronic kidney disease., Conclusion: Elbasvir/grazoprevir was highly effective in individuals with HCV genotype 1b infection in a large national Veterans Affairs clinical setting.

Purpose: To obtain an up-to-date overview of the measurement of patient experience of switching biologic treatment in patients with inflammatory arthritis (IA) or ulcerative colitis (UC). Secondary objectives included summarizing the types of patient-reported outcomes (PROs) used (if any), and related findings; and summarizing medical and non-medical reasons for treatment switch and/or discontinuation., Methods: A systematic literature review (SLR) was performed, searching Medline and Embase for relevant publications., Results: In total, 70 relevant publications were identified. While the majority of these reported reasons for switching and/or discontinuing treatment, only four provided information explicitly regarding patient-reported experience of switching biologic treatment. All four utilized ranking tools to assess patient experience of switching biologic treatment. The most common reason for switching and/or discontinuing treatment was loss of efficacy, while the least common reason was patient preference., Conclusion: Although the number of available treatments in IA and UC have increased, there is a sparsity of information regarding patient-reported experience of switching biologic treatment. Further research regarding patient preference and/or experience would benefit this therapeutic area and help guide treatment choices., Competing Interests: KL, JD, AS, and MD conducted this work as part of their employment with ICON plc. CMB and AP are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. The authors report no other conflicts of interest in this work., (© 2020 Luttropp et al.)

Background & Aims: Randomized controlled trials of EBR/GZR have reported high treatment efficacy, safety and tolerability in patients undergoing dialysis. However, real world effectiveness data for EBR/GZR in this population is lacking. We evaluated the effectiveness of EBR/GZR in an HCV-infected population with all stages of CKD including dialysis compared with control patients with estimated glomerular filtration rate (eGFR) ≥60 in the US Department of Veterans Affairs (VA)., Methods: We conducted a retrospective cohort study of patients with chronic HCV genotype 1 infection with EBR/GZR prescriptions dispensed during February 1, 2016-August 31, 2017 in 128 VA Medical Centers. We collected patient information regarding history of dialysis, end stage renal disease (ESRD), and/or eGFR values. We measured SVR based on undetectable HCV RNA at least 4 weeks after the completion of treatment. We examined SVR rates by CKD stage compared to control patients and within patient subgroups using logistic regression models., Results: We identified 5961 patients (42.5% genotype 1a, 55.0% genotype 1b) who met eligibility criteria and completed a EBR/GZR treatment course (≥11 weeks). Approximately 73.2% (n = 4361) had eGFR ≥60 who served as control patients, 14.4% (n = 860) had Stage 3 CKD, and 12.4% (n = 740) had Stage 4-5 CKD or ESRD. Of patients with Stage 4-5 CKD/ESRD, 76.1% underwent dialysis (n = 563). The overall SVR was 96.7% in all patients, 96.4% for eGFR≥60, 98.3% in Stage 3 CKD, and 96.5% in Stage 4-5 CKD/ESRD. No statistically significant differences were found in the SVR rates in patients with or without dialysis in the Stage 4-5 CKD/ESRD patients (adjusted OR 0.91; 95% CI 0.56-1.47 and OR 1.74; 95% CI 0.63-4.81) compared with those with eGFR≥60., Conclusion: We found EBR/GZR was effective in patients with HCV GT1 infection regardless of CKD severity or receipt of dialysis in the US VA population., Competing Interests: Declaration of competing interest Dr. Kanwal received research grant funding to complete this work. Drs. Kramer, Kanwal, and El-Serag have received research funding from Merck & Co. and Gilead Sciences for studies outside this work. Dr. Puenpatom is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and shareholder in Merck & Co., Inc., Kenilworth, NJ, USA. Dr. Kramer has received grant support from Merck Sharp & Dohme Corp.Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Data on initiation and utilization of direct-acting antiviral therapies for hepatitis C virus infection in the United States are limited. This study evaluated treatment initiation, time to treatment, and real-world effectiveness of direct-acting antiviral therapy in individuals with hepatitis C virus infection treated during the first 2 years of availability of all-oral direct-acting antiviral therapies., Methods: A retrospective cohort analysis was undertaken using electronic medical records and chart review abstraction of hepatitis C virus-infected individuals aged >18 years diagnosed with chronic hepatitis C virus infection between January 1, 2014, and December 31, 2015 from the Indiana University Health database., Results: Eight hundred thirty people initiated direct-acting antiviral therapy during the 2-year observation window. The estimated incidence of treatment initiation was 8.8%±0.34% at the end of year 1 and 15.0%±0.5% at the end of year 2. Median time to initiating therapy was 300 days. Using a Cox regression analysis, positive predictors of treatment initiation included age (hazard ratio, 1.008), prior hepatitis C virus treatment (1.74), cirrhosis (2.64), and history of liver transplant (1.5). History of drug abuse (0.43), high baseline alanine aminotransferase levels (0.79), hepatitis B virus infection (0.41), and self-pay (0.39) were negatively associated with treatment initiation. In the evaluable population (n = 423), 83.9% (95% confidence interval, 80.1-87.3%) of people achieved sustained virologic response., Conclusion: In the early years of the direct-acting antiviral era, <10% of people diagnosed with chronic hepatitis C virus infection received direct-acting antiviral treatment; median time to treatment initiation was 300 days. Future analyses should evaluate time to treatment initiation among those with less advanced fibrosis., Competing Interests: P.Y.K. has received grants from the Regenstrief Institute relevant to the work under consideration, and has also received grants and personal fees from AbbVie, BMS, Merck, and Janssen; grants from Gilead and Target Registries; and personal fees from Quest. A.P. is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and holds stock in Merck and Co., Inc., Kenilworth, NJ, USA. This does not alter our adherence to PLOS ONE policies on sharing data and materials (as detailed online in the guide for authors http://journals.plos.org/plosone/s/competinginterests). Z.Z., S.L.H, A.A.K., and D.M. declare no conflicts of interest.

Background: Direct-acting anti-viral (DAA) therapy may have a beneficial role in extrahepatic manifestations of hepatitis C virus (HCV) infection. However, the available data are limited., Aim: To examine the effects of DAA treatment on the risk of several extrahepatic manifestations of HCV., Methods: We conducted a retrospective cohort study of patients from the US Department of Veterans Affairs Corporate Data Warehouse who had a positive HCV RNA test and received first course of DAAs between 2012 and 2016. We calculated incidence rates by sustained virological response (SVR) status for six extrahepatic manifestations, and effect of SVR on these conditions was evaluated in adjusted Cox regression models., Results: Of the 45 260 patients treated with DAA with mean follow-up of 2.01 years, 41 711 (92.2%) experienced SVR. Incidence rates ranged from 0.17/1000 PY for porphyria cutanea tarda to 21.04/1000 PY for diabetes in the SVR group and 0.51/1000 PY for porphyria cutanea tarda to 23.11/1000 PY for diabetes in the no SVR group. The risk was reduced with SVR for mixed cryoglobulinaemia (adjusted HR (aHR) = 0.23; 95% CI 0.10-0.56), glomerulonephritis (aHR = 0.61; 95% CI 0.41-0.90) and lichen planus (aHR = 0.46; 95% CI 0.30-0.70), but not for non-Hodgkin's lymphoma (aHR = 0.86; 95% CI 0.52-1.43) or diabetes (aHR = 0.98; 95% CI 0.81-1.19). Non significant risk reduction was seen for porphyria cutanea tarda (aHR = 0.33; 95% CI 0.11-1.03)., Conclusions: Successful DAA treatment resulting in SVR was associated with significant reductions in the risk of mixed cryoglobulinaemia, glomerulonephritis, lichen planus and possibly porphyria cutanea tarda, but not non-Hodgkin's lymphoma or diabetes., (© 2019 John Wiley & Sons Ltd.)

Background: Newer direct acting antiviral agents against HCV (DAAs) are safe and efficacious in persons with chronic kidney disease (CKD). Whether approval of newer DAAs has resulted in more persons with CKD initiating HCV treatment remains unknown., Methods: We identified HCV+ persons in ERCHIVES between October 1999 and July 2016. We excluded HIV+ and HBsAg+ and those with missing baseline HCV RNA and baseline eGFR data. We identified persons initiated on any approved DAA-regimen through July 2016, by CKD stage. Logistic regression analyses were used to determine factors associated with treatment initiation., Results: Among 83 706 evaluable persons, 21.1% initiated treatment. Rates differed significantly by CKD stage: 22.1% for eGFR>90 mL/min/1.73 m 2 and CKD stage-2; 14.9% for CKD stage 3; and 8.0% for CKD stage-4/5. Those with CKD stage-3 were 33% less likely and those with CKD stage-4/5 were 60% less likely to initiate treatment with a DAA compared with those with baseline eGFR>90 mL/min/1.73 m 2 . Treatment initiation was less likely in HCV genotype 2 (OR 0.59; 95%CI 0.53,0.66) or 3 (OR 0.53; 95%CI 0.47,0.61) and those with diabetes (OR 0.87, 95% CI 0.81,0.94), cardiovascular disease (OR 0.77, 95% CI 0.70,0.84), alcohol abuse or dependence (OR 0.74, 95% CI 0.70,0.79) or cirrhosis (OR 0.86, 95% CI 0.80,0.92) at baseline., Conclusions: Persons with more advanced CKD are less likely to receive treatment for HCV despite recent data on safety and efficacy. Strategies are needed to improve treatment rates in the HCV/CKD population., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

Background: Hepatitis C virus (HCV) is a risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD). Direct-acting antiviral agents (DAAs) have improved HCV management in CKD patients, however real-world clinical practice data are limited., Objective: This study examined the prevalence of CKD among HCV patients receiving oral DAAs in a real-world setting. Comorbidities, early discontinuation rates, and healthcare costs were compared between patients with and without CKD., Methods: Patients with HCV who were treated with oral DAAs between November 2013 and June 2015, and who were enrolled in a US health plan, were identified. Early discontinuation was calculated based on observed versus expected treatment duration, and expected treatment duration was based on genotype, initial treatment regimen, baseline cirrhosis, and prior treatments. Healthcare costs were calculated during the baseline, treatment, and post-treatment periods., Results: This study included 3438 patients receiving oral DAAs, of whom 6.9% had a CKD diagnosis. CKD patients were more often male (70.8 vs. 62.9%, p = 0.02) and older (mean age 62.0 vs. 58.8 years, p < 0.001) than non-CKD patients, and had a higher prevalence of most comorbidities. Among early discontinuers, CKD patients were more likely to experience anemia (19.4 vs. 7.7%, p = 0.028)., Conclusions: Few patients with CKD receive DAA treatment for HCV infections. HCV patients with CKD had significantly more comorbidities and higher baseline healthcare costs than patients without CKD. Compared with non-CKD patients, CKD patients were equally likely to discontinue DAA treatment early but had higher rates of anemia. This study highlights the need for more renal-friendly HCV therapies.

Background: The utilization of high-potency opioids is an important component of chronic pain management, and appropriate utilization of these medicines is a common concern of payers. Two of the most commonly prescribed oral long-acting opioids, oxycodone controlled-release (CR) and oxymorphone extended-release (ER), are FDA-approved for twice-daily dosing, which equates to a theoretical average consumption (DACON) of 2 tablets per day. DACON values greater than 2 have budget and policy implications for managed care pharmacists., Objectives: To assess from the perspective of the pharmacy benefit decision maker the DACONs of oxycodone CR and oxymorphone ER., Methods: The main outcome measure for the analysis was DACON. Pharmacy and medical claims data from a large commercially insured population (i3 InVision Data Mart database) were analyzed to identify patients with at least 1 pharmacy claim for either oxycodone CR or oxymorphone ER from July 1, 2007, to September 30, 2009. After an initial 30-day titration period, all subjects included in the study had 1 or more claims totaling at least a 90-day supply of either study drug during the subsequent 90 days (DACON measurement period). Patients were excluded if there was evidence of a switch from one to the other study opioid during the 90-day measurement period. There were no limitations on the use of other opioids, either short- or long-acting, during either the DACON measurement period or the previous 6 months (baseline period). In addition, patients were excluded if the enrollee was younger than 18 years old, pregnant, did not have continuous insurance coverage for the 6 months before and after the start of the 90-day DACON measurement, or were enrolled in an HMO plan. Bivariate analyses were performed with between-group differences in DACON values assessed using t-tests and Wilcoxon rank sum tests. Patient characteristics including age, sex, geographic location, and baseline Charlson Comorbidity Index (CCI) for each drug group were evaluated descriptively using either the Pearson chi-square test or t-test. Multivariate analyses were conducted using generalized linear models (GLM) to adjust for the observed heterogeneity among patients in the observational database. For the GLMs, the gamma distribution and log link function were chosen to account for non-normal distributions of DACON. Independent variables included study drug, tablet strengths, age, sex, CCI, the maximum days gap between prescription refills during the DACON measurement period, and other opioid medication use. Several sensitivity analyses were conducted to verify all findings., Results: The final analyses were conducted on 6,567 oxycodone CR patients and 796 oxymorphone ER patients. The unadjusted DACON mean value for the highest strength of oxycodone CR 80 milligrams (mg) was 3.9, compared with 2.9 for oxymorphone ER 40 mg (P < 0.001); mean DACON values were 3.0 versus 2.4, respectively, for lower strengths (P < 0.001) and 3.1 versus 2.5 for all strengths (P < 0.001). After adjusting for age, sex, CCI, maximum gap days, and other opioid medication use, a risk-adjusted mean difference in DACON remained, with oxycodone CR patients receiving on average 0.6 tablets more per day than those dispensed oxymorphone ER (P < 0.001). The direction, magnitude, and statistical significance of these differences were essentially unchanged in sensitivity analyses., Conclusions: On average during a 90-day time period, patients taking oxymorphone ER consumed 0.6 fewer tablets per day than did patients taking oxycodone CR. Further research is necessary to see if this difference amounts to cost savings for health plans that provide prescription reimbursement for patients with chronic pain syndromes.