Molnupiravir Use Among Patients with COVID-19 in Real-World Settings: A Systematic Literature Review.

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.

COVID-19 continues to be a major source of morbidity and mortality. Throughout the pandemic, many countries authorized various therapies for the treatment of individuals presenting with mild-to-moderate COVID-19 and at high risk of progression to severe disease. Some of these therapies have since been rendered ineffective due to the emergence of Omicron variants in late 2021. The objective of the current study was to conduct a systematic literature review to assess real-world evidence on the effectiveness of molnupiravir, including effectiveness against COVID-19 caused by Omicron variants, to supplement the findings of the MOVe-OUT clinical trial and further inform on the potential clinical benefit and utility of this antiviral agent. Nine studies were included in the systematic literature review. We found that treatment with molnupiravir 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 molnupiravir-treated and control groups may have led to underestimation of the effectiveness of molnupiravir in many observational studies. In summary, real-world effectiveness studies provide additional evidence supporting the continued benefits of molnupiravir in non-hospitalized adults with COVID-19.

Impact of Molnupiravir Treatment on Patient-Reported COVID-19 Symptoms in the Phase 3 MOVe-OUT Trial: A Randomized, Placebo-Controlled Trial.

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.

Prevalence of Potential Drug-drug Interactions With Ritonavir-containing COVID-19 Therapy in the United States: An Analysis of the National Health and Nutrition Examination Survey.

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.

Prevalence of potential drug-drug interactions with ritonavir-containing COVID-19 therapy.

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.

Health-related quality of life in people receiving opioid agonist treatment and treatment for hepatitis C virus infection.

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.

Progression of the FIB-4 index among patients with chronic HCV infection and early liver disease.

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.

Effectiveness of Golimumab as Second Anti-TNFα Drug in Patients with Rheumatoid Arthritis, Psoriatic Arthritis and Axial Spondyloarthritis in Italy: GO-BEYOND, a Prospective Real-World Observational Study.

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.

Cost-Effectiveness Analysis of Molnupiravir Versus Best Supportive Care for the Treatment of Outpatient COVID-19 in Adults in the US.

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.

Effect of Molnupiravir on Biomarkers, Respiratory Interventions, and Medical Services in COVID-19 : A Randomized, Placebo-Controlled Trial.

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.

Treatment of hepatitis C virus infection in people with opioid use disorder: a real-world study of elbasvir/grazoprevir in a US Department of Veterans Affairs population.

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.

Health-Care and Societal Costs Associated with Non-Persistence with Subcutaneous TNF-α Inhibitors in the Treatment of Inflammatory Arthritis (IA): A Retrospective Observational Study.

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.

Treatment Persistence in Patients Cycling on Subcutaneous Tumor Necrosis Factor-Alpha Inhibitors in Inflammatory Arthritis: A Retrospective Study.

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.

Evaluating the power of the causal impact method in observational studies of HCV treatment as prevention.

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.

Cost-Utility of All-Oral Direct-Acting Antiviral Regimens for the Treatment of Genotype 1 Chronic Hepatitis C Virus-Infected Patients in Hong Kong.

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.

Efficacy and safety of elbasvir/grazoprevir in treatment-naive Chinese adults with hepatitis C virus infection: A randomized trial.

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.