Initial uptake, time to treatment, and real-world effectiveness of all-oral direct-acting antivirals for hepatitis C virus infection in the United States: A retrospective cohort analysis

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

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 &lt;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 &gt;3.25 during follow-up. Survival analyses were used to assess time to FIB-4 &gt;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 &lt;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.</p

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 &lt; 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

Real-world effectiveness and persistence of golimumab as second-line anti-TNFα drug in rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis patients in Italy: GO-BEYOND, a 12-month prospective observational study

A high proportion of patients may fail a first-line anti-TNF drug, necessitating the switch to another anti-TNF treatment. After 12 months of GLM treatment, 80% of RA patients achieved low disease activity (LDA), 37.1% with PsA achieved minimal disease activity and 55.3% with axSpA achieved LDA while persistence at 12 months in all patients was 77.7%. In this 1-year analysis of the GO-BEYOND study in Italy, GLM had a favorable benefit: risk profile and high retention rate in patients with PsA, RA and axSpA

Adipokines: Linking metabolic syndrome, the immune system, and arthritic diseases

Metabolic syndrome (MetS) represents a cluster of metabolic and cardiovascular complications, including obesity and visceral adiposity, insulin resistance, dyslipidemia, hyperglycemia and hypertension, which directly increase the risk of cardiovascular diseases (CVD) and diabetes mellitus type 2 (DM2). Patients with arthritic diseases, such as rheumatoid arthritis and osteoarthritis, have a higher incidence of CVD. Although recent advances in the treatment of arthritic diseases, the incidence of CVD remains elevated, and MetS has been identified as a possible link between CVD and arthritic diseases. Chronic low-grade inflammation associated with obesity has been established as a significant contributing factor to the increased prevalence of MetS. Adipokines, which play important physiological roles in metabolic activities contributing to the pathogenesis of MetS, are also involved in the regulation of autoimmune and/or inflammatory processes associated with arthritic diseases. Therefore, MetS and dysregulated secretion of pro-inflammatory adipokines have been recognized as a molecular link between CVD and arthritis diseases. In the present paper, we review recent evidence supporting the role played by adipokines, in particular leptin, adiponectin, and lipocalin-2, in the modulation of the immune system, MetS and arthritic diseases. The underlying cellular and molecular mechanisms are discussed, as well as potential new therapeutic strategies.Acknowledgments: OG and FL are Staff Personnel of Xunta de Galicia (Servizo Galego de Saude, SERGAS) through a research-staff stabilization contract (ISCIII/SERGAS). VF is a “Sara Borrell” Researcher funded by ISCIII and FEDER (CD16/00111). RG is a “Miguel Servet” Researcher funded by Instituto de Salud Carlos III (ISCIII) and FEDER. CRF is a pre-doctoral research scholar funded by ISCIII and FEDER (Exp.18/00188). OG, MAGG, and RG are members of RETICS Programme, RD16/0012/0014 (RIER: Red de Investigación en Inflamación y Enfermedades Reumáticas) via Instituto de Salud Carlos III (ISCIII) and FEDER. FL is a member of CIBERCV (Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares). The work of OG and JP (PI17/00409), RG (PI16/01870 and CP15/00007) and FL (PI15/00681 PI18/00821 and CB16/11/00226) were funded by Instituto de Salud Carlos III and FEDER. OG is a beneficiary of a project funded by Research Executive Agency of the European Union in the framework of MSCA-RISE Action of the H2020 Programme (Project number 734899). RG is beneficiary of a project funded by Mutua Madrileña 2018. AM wishes to acknowledge financial support from the European Structural and Social Funds through the Research Council of Lithuania (Lietuvos Mokslo Taryba) according to the activity ‘Improvement of researchers’ qualification by implementing world-class R&D projects’ of Measure No. 09.3.3-LMT-K-712 (grant application code: 09.3.3-LMT-K-712-01-0157, agreement No. DOTSUT-215) and the new funding programme: Attracting Foreign Researchers for Research Implementation (2018–2022). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript

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 &lt;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 &gt;3.25 during follow-up. Survival analyses were used to assess time to FIB-4 &gt;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 &lt;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