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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.

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 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., A sustained virologic response was achieved by 96.7% (146/151) of treatment‐naive participants with hepatitis c virus infection receiving elbasvir/grazoprevir (50 mg/100 mg) for 12 weeks. Patient‐reported outcomes indicate improved quality of life following clearance of HCV.

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.

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.

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.

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. Adult Swedish biologic-naive 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. 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]). Among biologic-naive 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.

Elbasvir/grazoprevir (EBR/GZR) is an all-oral direct-acting antiviral agent (DAA) with high sustained virologic response (SVR) in clinical trials. This study’s primary objective was to evaluate effectiveness of EBR/GZR among HCV-infected patients in a real-world clinical setting. We conducted a nationwide retrospective observational cohort study of HCV-infected patients in the US Department of Veterans Affairs (VA) using the VA Corporate Data Warehouse. The study population included patients with positive HCV RNA who initiated EBR/GZR from February 1 to August 1, 2016. We calculated the 95% confidence interval for binomial proportions for SVR overall and by demographic subgroups. Clinical and demographic characteristics were also evaluated. We included 2,436 patients in the study cohort. Most were male (96.5%), African-American (57.5%), with mean age of 63.5 (SD=5.9), and 95.4% infected with genotype (GT) 1 [GT1a (34.7%), GT1b (58.6%)]. Other comorbidities included diabetes (53.2%), depression (57.2%), and HIV (3.0%). More than 50% had history of drug or alcohol abuse (53.9% and 60.5%, respectively). 31.4% of the cohort had cirrhosis. A total of 95.6% (2,328/2,436; 95% CI: 94.7%−96.4%) achieved SVR. The SVR rates by subgroups were: male, 95.5% (2245/2350); female, 96.5% (83/86); GT1a, 93.4%, GT1b, 96.6%, GT4, 96.9%, African-American, 95.9% (1,342/1,400); treatment-experienced, 96.3% (310/322); cirrhosis, 95.6% (732/766); stage 4–5 CKD, 96.3% (392/407); and HIV, 98.6% (73/74). SVR rates were high overall and across patient subgroups regardless of gender, race/ethnicity, cirrhosis, renal impairment, or HIV. This study provided important data regarding the effectiveness of EBR/GZR in a large clinical setting.

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 m2 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 m2 . 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.

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

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

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.

Background: Biologics have transformed the treatment of inflammatory arthritis (IA).However, the complexity of disease management has increased with the introduction of biosimilars and novel treatments. Hence, patient experience and satisfaction has become increasingly important in treatment individualization. Objectives: Firstly, to assess to what extent IA patient experience of switching biologics is measured in the literature; secondly, to summarize patient-reported outcomes (PROs) as well as medical/non-medical reasons associated with switching. Methods: A systematic literature review (SLR) was performed in accordance with PRISMA guidelines. EMBASE and MEDLINE were searched for relevant publications from 2013 to present day, together with relevant conference abstracts from 2018 (ACR-ARHP, EULAR, and ISPOR). Studies published in English including either a) patient-reported outcomes (PROs) associated with switching biologics, or b) reasons for switching and/or discontinuing biologics treatment as noted by health care professionals and/or patients were included. The scope was limited to European and North American populations. While the initial search included patient populations with ulcerative colitis in addition to IA patients, results presented within this abstract focus on IA populations only. Results: After initial screening of 1781 abstracts, sixty-eight studies including IA patients were identified for inclusion in the analysis. Of the remaining studies, 39/68 (57%) included ≥1 treatment switch. The majority of studies were conducted in Europe (36/39; 92%), with the proportion of female patients ranging between 12-90%. Thirteen studies (18%) included at least one PRO, 4 of which only recorded PROs prior to switch (6%). The most commonly reported PRO was PGA/VAS, followed by HAQ and questions asking patients to rank their switching experience using various pre-defined categories (Figure 1). While the most common reasons for discontinuing treatment, which may or may not include switching, was provided in 33 studies (loss of efficacy and safety), reasons strictly for switching are infrequently reported. Conclusion: Patient satisfaction is important, as it has been linked to clinical safety, treatment effectiveness, and adherence (Doyle et al., 2013). However, this SLR highlights a notable lack of information regarding patient-reported experience of switching biologic treatment. The PROs reported in a minority of studies encompass several regions related to patient well-being – such as pain, fatigue, etc. – but provides very limited information on the experience of switching. Hence, to improve disease management and treatment individualization, further research is required. Reference [1] Doyle, et al. A systematic review of evidence on the links between patient experience and clinical safety and effectiveness. BMJ Open, 2013. Disclosure of Interests: Mary Dozier Consultant for: Mary Dozier is an employee of ICON PLC and has received consulting fees from Merck & Co., Inc, Karin Luttropp Consultant for: Karin Luttropp is an employee of ICON PLC and has received consulting fees from Merck & Co., Inc, Axel Svedbom Consultant for: Axel Svedbom is an employee of ICON PLC and has received consulting fees from Merck & Co., Inc, Johan Dalen Consultant for: Johan Dalen is an employee of ICON PLC and has received consulting fees from Merck & Co., Inc, Christopher Black Shareholder of: Christopher Black is a shareholder in Merck & Co., Inc., Kenilworth, NJ USA, Employee of: Christopher Black is an employee of Merck & Co., Inc., Kenilworth, NJ USA, Amy Puenpatom Shareholder of: Amy Puenpatom is a shareholder of Merck & Co., Inc., Kenilworth, NJ USA, Employee of: Amy Puenpatom is an employee of Merck & Co., Inc., Kenilworth, NJ USA

BackgroundData 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.MethodsA 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.ResultsEight 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.ConclusionIn the early years of the direct-acting antiviral era

Background:Patient persistence with biologic treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) (collectively inflammatory arthritis, IA) may be considered a proxy for efficacy, safety and treatment satisfaction. Patients who discontinue their first line of subcutaneous tumor necrosis factor alpha inhibitors (SC-TNFis) and switch to at least one subsequent line of SC-TNFi can be defined as cyclers.Objectives:To assess persistence by line of therapy in Swedish IA patients cycling on SC-TNFis.Methods:Using data from the Swedish Health Data Registers, adult IA patients initiating treatment with any available SC-TNFi (adalimumab, etanercept, certolizumab, or golimumab) between May 1st2010 and October 31st2016 were eligible for inclusion. Treatment persistence was derived using information from filled prescriptions (e.g. dispensing date, pack information, and defined daily dose) with a 60-day grace period. Analyses were restricted the first two lines of treatments (i.e. 1stand 2nd) in patients defined as SC-TNFi cyclers. Persistence estimates across treatment lines were assessed graphically using Kaplan-Meier curves. 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). Covariates in the adjusted analysis included age, gender, diagnosis, year of treatment initiation, comorbidities, co-medication, and the number of specialized outpatient care visits and inpatient stays.Results:Of 11,668 patients initiating SC-TNFi treatment, 3,181 patients were identified as cyclers. Among these, a majority were female (68%) with a mean age of 50 years; 46%, 28%, and 26% were diagnosed with RA, AS and PsA, respectively. Figure 1 indicated that, among cyclers, persistence with second line treatment was higher compared to first line treatment persistence. This finding was confirmed by the analyses accounting for intrapatient dependence. Both the unadjusted and the adjusted analyses showed that the relative risk of discontinuing SC-TNFi treatment were significantly lower in 2ndline compared to 1stline (Hazard Ratio [HR]; 0.60 [0.57, 0.63] and 0.59 [0.56, 0.62], respectively). This finding was also consistent across IA indications (Table 1).Table 1.Relative risk of discontinuing subcutaneous Tumor Necrosis Factor-α inhibitor treatment for IA in 2nd line treatment compared to 1st line treatment, by analysis populationAnalysis populationNUnadjusted analysis, HR [95%CI]Adjusted analysis, HR [95%CI]Cyclers overall3,1810.60 [0.57, 0.63]0.59 [0.56, 0.62]RA1,4790.62 [0.57, 0.67]0.61 [0.56, 0.66]PsA8910.60 [0.54, 0.67]0.59 [0.53, 0.65]AS8110.58 [0.52, 0.64]0.55 [0.50, 0.61]HR: Hazard Ratio, 95%CI: 95% confidence intervalFigure 1.Persistence, among cyclers, with subcutaneous Tumor Necrosis Factor-α inhibitors treatment for IA by line of treatmentConclusion:In this preliminary analysis of IA patients cycling on SC-TNFis, persistence was greater in 2ndline compared to 1stline treatment. The finding was consistent across all IA indications. Hence, IA patients who fail to respond, lose response, or for other reasons discontinue their 1stline treatment may still benefit from switching to an alternative SC-TNFi as a 2ndline therapy.Disclosure of Interests:Johan Dalén Consultant of: Merck & Co., Inc. in conjunction with the development of this abstract. JD is an employee of ICON plc. ICON plc have received funding from several pharmaceutical companies involved in the marketing products for treatment of inflammatory arthritis., Amy Puenpatom Shareholder of: shareholder at Merck & Co, Inc, Employee of: Employed at Merck & Co, Inc., Karin Luttropp Consultant of: Merck & Co., Inc. in conjunction with the development of this abstract. KL is an employee of ICON plc. ICON plc have received funding from several pharmaceutical companies involved in the marketing products for treatment of inflammatory arthritis., Christopher Black Shareholder of: I own shares of MSD, Employee of: I am an employee of MSD

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.

Background Chronic kidney disease (CKD) was a relative contraindication to hepatitis C virus (HCV) treatment in the interferon/ribavirin era. Aim To determine the efficacy, tolerability and safety of sofosbuvir/ledipasvir (SOF/LDV) and paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens in persons with CKD. Methods We identified persons initiated on a SOF/LDV or PrOD regimen from October 30, 2014 to April 30, 2016. We excluded those with missing HCV genotype or eGFR values. We determined treatment completion and sustained virologic response (SVR) rates, and proportion developing worsening renal function or grade 3/4 haematologic toxicity. Results Among 13 663 persons on SOF/LDV±ribavirin, 14% and 1% persons had CKD Stage 3 and 4-5 respectively, 67.8% completed treatment, 98.2% achieved SVR. Treatment completion or SVR rates did not decline with advanced CKD or ribavirin administration. Among 3961 persons on PrOD±ribavirin, 9% and 3% persons had CKD Stage 3 and 4-5, respectively, 74.0% completed treatment and 98.2% achieved SVR. A decrease in treatment completion rates was seen in CKD stage 4-5 and those on ribavirin, but this did not impact SVR rates. A >10 mL/min/1.73 m2 drop in eGFR from baseline was observed in 30%-38% of persons with baseline eGFR ≥60 mL/min/1.73 m2 , but in only 0%-6% with CKD4-5. Grade 3/4 anaemia was more frequent in persons with CKD4-5, but ribavirin co-administration did not appear to affect this. Conclusions SOF/LDV and PrOD achieved high SVR rates in CKD population. Treatment completion rates were lower than expected. A decline in eGFR and development of anaemia were observed in a substantial proportion of persons, but the clinical implications remain unclear.

Chronic pain patients may be subject to polypharmacy because of long-term pharmacological pain treatment and additional comorbidities. Many chronic pain patients expose themselves to potential drug-drug interactions (DDIs) and these interactions can have unintended and severe consequences. Prevalence and costs associated with DDIs are inconsistent and has led to an inadequate level of awareness among the medical community; therefore, it has become necessary to re-evaluate the rates of DDIs in chronic pain patients. Utilizing medical and prescription claims databases, five studies were conducted to assess the health care utilization of and associated financial payments for patients18 years with chronic noncancer pain. The studies evaluated drug-drug exposures with the potential to cause DDIs specifically occurring through the CYP450 enzyme system. The studies reported that drug-drug exposures are prevalent, costly and can occur in any age group and that physicians should consider ways to limit their patients' exposure to potential DDIs.

Background Newer directing antiviral agents against HCV (DAAs) are safe and efficacious in persons with chronic kidney disease (CKD). Whether availability of these newer DAAs has resulted in more persons with CKD initiating HCV treatment remains unknown. Methods We identified HCV+ persons in ERCHIVES. We excluded HIV+ and HBsAg+ and those with missing HCV RNA and eGFR data. We determined the CKD stage according to National Kidney Foundation criteria. We determined the number of persons initiated on any of the approved DAA-regimen (defined as >14 days of DAA prescription). Logistic regression analyses was used to determine factors associated with treatment initiation. Results Among 76,513 evaluable persons, 21.1% initiated DAA treatment. Initiation rates differed significantly by CKD stage: 21.1% (15,136/68,469) for eGFR>90mL/minute/1.73m2 and CKD stage-2; 14.0% 9853/6,086) for CKD stage 3; and 7.6% (148/1,958) for CKD stage-4/5. Those with CKD stage-3 were 35% less likely and those with CKD stage-4/5 were 65% less likely to initiate treatment with a DAA compared with those with baseline eGFR>90mL/minute/1.73m2. Those with Body Mass Index (BMI)>30 were more likely to initiate treatment (OR 1.24, 95% CI 1.19,1.29). Treatment initiation was less likely in HCV genotype 2 or 3 and those with diabetes (OR 0.82, 95% CI 0.78,0.86), cardiovascular disease (OR 0.73, 95% CI 0.68,0.78), alcohol abuse or dependence (OR 0.75, 95% CI 0.72,0.78) or cirrhosis (OR 0.85, 95% CI 0.80,0.89) at baseline. Conclusion Persons with more advanced CKD are less likely to receive treatment for HCV. Strategies are needed to improve treatment rates in the HCV/CKD population. Disclosures A. Butt, Merck: Investigator, Grant recipient. A. Puenpatom, Merck: Employee, Salary. J. M. Arduino, Merck: Employee, Salary. R. Kumar, Merck: Employee, Salary

Background Chronic kidney disease (CKD) was a relative contraindication to HCV treatment in the interferon/ribavirin era due to poor tolerability and lower efficacy. Our aim was to determine the effectiveness treatment completion, and safety of sofosbuvir/ledipasvir (SOF/LDV) and paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens in persons with CKD. Methods We identified all persons started on a SOF/LDV or PrOD regimen in ERCHIVES before 30 April 2016. We excluded those with missing HCV genotype, or eGFR values. We determined treatment completion, sustained virologic response (SVR) rates and proportion of persons with worseningrenal function or developing grade 3/4 anemia. Results We identified 9,837 persons on SOF/LDV, 3,826 on SOF/LDV+RBV, 1,017 on PrOD and 2,944 on PrOD+RBV. Genotype 1a was the predominant genotype for SOF/LDV+RBV (77.3% no RBV; 70.0% with RBV) and PrOD+RBV (79.5%) groups, while only 4.3% of PrOD with no RBV group were genotype 1a. Among treated patients, the prevalence of patients with stage 4–5 CKD was 0.8% (SOF/LDV + RBV), 1.1% (SOF/LDVno RBV), 2.2% (PrOD +RBV) and 5.4% (PrOD no RBV). Among 13,663 total persons on SOF/LDV, 67.8% completed treatment while the treatment completion rate of those on PrOD was 74.0% (N = 2,932/3,961) (Table 1). The overall SVR rates of persons on SOF/LDV or PrOD regimens were 96.3%. A drop in treatment completion rates was seen in CKD stage 4–5 and those on PrOD+RBV, but the impact of RBV on SVR was unclear. While about one-third of the persons with a CKD stage 1–2 experienced a >10 mL/minute/1,73m2, about 15% decline among those with CKD stage 3. The incidence of grade3/4 anemia by CKD stages increased significantly across the treatment groups. Grade 3/4 anemia ranged from 9.7% (SOF/LDV) to 21.8% (PrOD) among patients with CKD stage 4–5 (Table 2). Conclusion SVR rates among persons treated with SOF/LDV or PrOD were high in the CKD population despite 22% not completing the treatment regimen. Incidence of grade3/4 anemia increased significantly in CKD stage 4–5 across the treatment groups. Disclosures A. Butt, Merck: Investigator, Grant recipient.A. Puenpatom, Merck: Employee, Salary. J. M. Arduino, Merck: Employee, Salary. R. Kumar, Merck: Employee, Salary

Patients with osteoarthritis (OA) taking at least one CYP450-metabolized opioid concurrently with another CYP450-metabolized medication experience a drug–drug exposure (DDE), which puts them at risk of a pharmacokinetic drug–drug interaction (PK DDI). This study compared patients with and without such an incident DDE to determine healthcare utilization and associated payments. Using a retrospective database analysis, the impact of DDEs was evaluated in terms of associated clinical events, healthcare services utilization (office visits, outpatient visits, ED visits, hospitalization), and payments in patient populations based on age (those under age 65 and those 65 years of age and older), during the 6 months after exposure. DDE patients had significantly more inpatient hospitalizations than no-DDE patients. Mean total payments at 6 months were significantly higher for both younger and older patients with DDE compared to similar patients without DDE ($9,469, SD = $12,192 vs. $8,382, SD = $14,078, respectively, for younger patients, resulting in a difference of $1,087, P

Chronic low back pain (cLBP) patients who take at least 1 CYP450-metabolized opioid analgesic agent concurrent with at least 1 other CYP450-metabolized medication experience a drug–drug exposure (DDE), which puts them at risk for a pharmacokinetic drug–drug interaction (PK DDI). This study compared utilization of healthcare resources and associated payments in cLBP patients with and without incident DDEs with the potential to cause PK DDIs. A retrospective database analysis examined the associated clinical events, healthcare utilization (measured in terms of claims for office visits, outpatient visits, emergency department visits, and hospitalization), and cost to the health plan, as defined as the sum of health plan payments for resources used. Patients were grouped into 2 cohorts by age (those under 65 and those 65 years and over). In the 6 months after exposure, total healthcare payments were significantly higher for DDE patients than those without DDEs (no-DDE), in both in the younger ($7,086, SD = $8,370) and $6,353, SD = $8,352, respectively, P

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.To assess from the perspective of the pharmacy benefit decision maker the DACONs of oxycodone CR and oxymorphone ER.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.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 (P0.001); mean DACON values were 3.0 versus 2.4, respectively, for lower strengths (P0.001) and 3.1 versus 2.5 for all strengths (P0.001). 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 (P0.001). The direction, magnitude, and statistical significance of these differences were essentially unchanged in sensitivity analyses.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.

Patients managing chronic non-cancer pain with cytochrome P450 (CYP450)-metabolized opioid analgesics who concurrently take another CYP450-metabolized medication experience a drug-drug exposure (DDE), which puts them at risk for a pharmacokinetic drug-drug interaction (PK DDI). This study examined the economic impact of incident DDEs with the potential to cause PK DDIs compared to similar patients without such exposure.This retrospective analysis used paid claims from a large, commercially insured population during January 1, 2004 through December 31, 2008.Propensity matching was used to control for baseline differences in comparisons between 85,043 exposed and 85,043 non-exposed patients.Comparisons yielded mean total costs 6 months after the DDEs that were significantly higher in subjects with DDE versus matched subjects without DDE [$8165 (SD $11,357) vs. $7498 (SD $11,668), respectively, p0.01] resulting in a difference of $667. This was driven by medical costs [$5520 (SD $10,505) vs. $5222 (SD $10,689), respectively, p0.01] a $298 difference, and total prescription costs [$2646 (SD $3262) vs. $2276 (SD $3907), respectively, p0.01] a $369 difference.The study design demonstrates associations only and cannot establish causal relationships. Further, relevant DDEs were not included if concurrent consumption occurred outside the index period and when CYP450 substances were consumed that are not reflected in pharmacy claims (herbals, over-the-counter medications).Since concurrent exposure to DDEs with the potential to cause PK DDIs may be relatively common, policy decisions-makers should consider the use of long-acting opioids that are not metabolized through the CYP450 pathway.

Patients taking more than one drug metabolized through the cytochrome P450 (CYP450) enzyme system experience a drug–drug exposure (DDE), which puts them at risk for a potential pharmacokinetic drug–drug interaction (DDI), defined as two or more drugs interacting in such a way that the effectiveness and/or toxicity of one or all drugs are changed. Any patient subjected to a DDE is at risk for a potentially serious DDI, the epidemiology of which has not been thoroughly studied. Many drugs are metabolized primarily via the CYP450 enzyme system, including certain opioids used to manage moderate to severe chronic pain. We conducted a retrospective analysis of a large commercial claims database and a Medicare database to assess the prevalence of DDEs among patients with osteoarthritis taking CYP450-metabolized opioids. The overall prevalence of DDEs in this population was 26%, with females more likely to experience DDEs than males (28.4% vs. 21.0%, respectively). The number of unique concurrent prescriptions at baseline, gender, age, and Charlson Comorbidity Index were statistically significant predictors of DDEs (P

Drug–drug interactions (DDIs) have been defined as two or more drugs interacting in such a way that the effectiveness and/or toxicity of one or all drugs are changed. Patients taking more than one drug metabolized through the cytochrome P450 (CYP450) enzyme system, including some, but not all, opioids experience a drug–drug exposure (DDE), which may result in a potentially dangerous DDI. Using a retrospective analysis of a large commercial claims database and a Medicare database, we evaluated DDEs that have the potential to cause DDIs among chronic low back pain (cLBP) patients on long-term opioid analgesia, which metabolizes through the CYP450 enzyme system, concomitant with other CYP450-metabolized drug(s). The overall prevalence of DDEs among cLBP patients was 27%. Women had a higher prevalence of DDEs (30.6% vs. 22% for men). Patients aged 45 to 55 and 56 to 64 years had the highest prevalence of DDEs (30.4% and 29.8%, respectively), followed by patients 34 to 45 years (27.9%). For patients > 65 years, the prevalence of DDEs was 23.1%. In general, the prevalence of DDEs was fairly consistent across age ranges in this population. This study suggests that DDEs are common in the cLBP population. When selecting an opioid to treat cLBP, physicians should consider the potential for exposure of these patients to drugs that might unfavorably interact and, for that reason, the use of opioids that do not rely on the CYP450 system as their primary means of metabolism might be worthy of consideration.

To compare healthcare resource utilization and costs of postherpetic neuralgia (PHN) patients initiating lidocaine patch 5% (lidocaine patch) or oral gabapentin/pregabalin.Patients with PHN diagnosis, or herpes zoster diagnosis and ≥30 days PHN-recommended treatment were selected from de-identified Medicaid claims data from Florida, Iowa, Missouri, and New Jersey, 1999-2007. Patients initiated monotherapy with lidocaine patch or gabapentin/pregabalin after PHN diagnosis, had continuous eligibility 6 months before (baseline) and 6 months after (study period) medication index date, and were ≥18 years old. Lidocaine patch patients were matched to gabapentin/pregabalin patients based on their propensity to initiate treatment. Study period resource utilization and costs from a Medicaid perspective were compared between treatment groups using univariate analysis.Matched patients were on average 61.3 years old, approximately 73% were women, and 55% had other painful conditions during the baseline period. 6-month per patient PHN-related prescription drug costs were similar for matched lidocaine patch (n=312) and gabapentin/pregabalin (n=312) patients ($854 vs. 820, p=0.75), while PHN-related medical costs appeared lower in the lidocaine patch group ($145 vs. 353, p=0.12). Furthermore, there were no statistically significant differences between treatment groups during the observation period in overall resource utilization, total prescription drug costs, and total medical costs per patient.In spite of higher list prices, PHN patients treated with lidocaine patch cost no more than patients treated with gabapentin or pregabalin in terms of overall healthcare costs over the 6-month study period. The study suggests that PHN-related medical costs may be lower among lidocaine patch patients.Findings are based on a Medicaid sample and may not be generalizable to all PHN patients.