Real‐world effectiveness of elbasvir/grazoprevir In HCV‐infected patients in the US veterans affairs healthcare system

Abstract

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 2436 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). 33.2% 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.

Effectiveness of Elbasvir/Grazoprevir in US Veterans with Chronic Hepatitis C Virus Genotype 1b Infection

“…We are also unable to determine if an 8-week regimen was intended for participants in this study or if a longer 12-week treatment duration was intended but stopped early. Data from the present analysis are consistent with those reported previously by Kramer and colleagues [11]. This study included 2436 patients from the VA, of whom 1428 had HCV genotype 1b infection.…”

“…In clinical trials, this combination therapy has demonstrated high rates of sustained virologic response (SVR) across a broad population of people with HCV infection, including those with chronic kidney disease, inherited blood disorders, compensated cirrhosis, and HCV/HIV co-infection [4][5][6][7][8][9][10]. The high SVR rates attained in elbasvir/grazoprevir clinical trials have also been replicated in the US Department of Veterans Affairs (VA) clinical practice populations, where an SVR rate of 95.6% was achieved in a large population comprised largely of male, black participants with HCV genotype 1 (genotype 1a, 34.7%; genotype 1b, 58.6%) infection, and more than 50% of whom had a history of drug or alcohol use [11]. The aim of this study was to assess elbasvir/grazoprevir regimens in individuals with chronic HCV genotype 1b infection from the VA population.…”

“…The aim of this study was to assess elbasvir/grazoprevir regimens in individuals with chronic HCV genotype 1b infection from the VA population. The current study population of 3371 patients includes the 1428 patients with genotype 1b infection previously reported by Kramer et al [11], but we extended the eligibility date range to incorporate more patients with HCV genotype 1b infection. This allowed for a more robust assessment of the effectiveness of elbasvir/grazoprevir in HCV genotype 1b patients from the VA population, including examining comorbidities and receipt of concomitant medications.…”

The effects of sustained virological response to direct‐acting anti‐viral therapy on the risk of extrahepatic manifestations of hepatitis C infection

“…The study also uses accurate, laboratory test‐based definitions of HCV infection and SVR as well as DAA treatment based on pharmacy records. The observed overall SVR of 92.1% is consistent with effectiveness data for DAA in community‐based studies and further adds to the internal validity of the results …”

Real‐world effectiveness of sofosbuvir/velpatasvir/voxilaprevir in 573 direct‐acting antiviral experienced hepatitis C patients

“…Despite the overall effectiveness of NS5A regimens, available treatments do not produce SVR in all patients. Up to 10% of genotype 1 patients who start ledipasvir/sofosbuvir do not achieve SVR and similar overall failure rates are reported for elbasvir/grazoprevir (2%‐8%) and ombitasvir/paritaprevir/ritonavir plus dasabuvir (1%‐11%) . In genotype 2 and 3 patients initiating sofosbuvir/velpatasvir, failure rates of 2% and 5%, respectively, were observed in clinical trials …”