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. 2020 Aug;40(8):1841-1852.
doi: 10.1111/liv.14537. Epub 2020 Jun 9.

Global real-world evidence of sofosbuvir/velpatasvir as simple, effective HCV treatment: Analysis of 5552 patients from 12 cohorts

Alessandra Mangia  1 , Scott Milligan  2 , Mandana Khalili  3 , Stefano Fagiuoli  4 , Stephen D Shafran  5 , Fabrice Carrat  6 , Denis Ouzan  7 , George Papatheodoridis  8 , Alnoor Ramji  9 , Sergio M Borgia  10 , Heiner Wedemeyer  11 , Ruggero Losappio  12 , Francisco Pérez-Hernandez  13 , Nicole Wick  2 , Robert S Brown Jr  14 , Pietro Lampertico  15 , Karen Doucette  5 , Ioanna Ntalla  16 , Heribert Ramroth  16 , Michael Mertens  16 , Kim Vanstraelen  16 , Juan Turnes  17
Affiliations

Global real-world evidence of sofosbuvir/velpatasvir as simple, effective HCV treatment: Analysis of 5552 patients from 12 cohorts

Alessandra Mangia et al. Liver Int. 2020 Aug.

Abstract

Background and aims: Achieving sustained virological response (SVR; cure) in hepatitis C patients using a simple regimen is key to making elimination by 2030 possible. In the largest real-world analysis to date, the effectiveness of pangenotypic, panfibrotic, single-tablet, sofosbuvir/velpatasvir (SOF/VEL) once-daily for 12 weeks was assessed in 12 clinical real-world cohorts from various geographical areas, settings and treatment practices. Factors affecting risk of not achieving SVR were assessed.

Methods: Adults treated with SOF/VEL 400/100 mg, without ribavirin, were included. All HCV patients reaching Week 12 or 24 post-treatment were assessed for SVR12/24. Factors associated with not achieving SVR12/24 for virological reasons were evaluated using logistic regression analysis.

Results: Overall, 5552 patients were included: 13.3% treatment-experienced; 20.7% compensated cirrhotic; 30.2% genotype 1; 29.5% genotype 2; 32.9% genotype 3; 4.7% genotype 4; 3.7% HIV coinfection; 13.4% current/former intravenous drug use. Of the 5196 patients evaluated for effectiveness, 98.9% achieved SVR12/24. High SVR12/24 rates occurred in all genotypes including genotype 3 (98.3%; 1649/1677) and in those with compensated cirrhosis (97.9; 1055/1078). Only 55 patients did not achieve SVR12/24 due to a virological reason; the only factor statistically significantly associated with an increased risk of not achieving SVR12/24 was compensated cirrhosis (P = .002). Overall, 6% (332/5552) of patients did not achieve SVR12/24 for non-virological reasons (67% lost to follow-up; 26.5% early treatment discontinuation).

Conclusions: In this large cohort, representative of clinical practice, a simple 12-week regimen of SOF/VEL without ribavirin resulted in high SVR12/24 rates in diverse patient populations, even among those with compensated cirrhosis.

Keywords: HCV elimination; Hepatitis C; heterogenous; real-world; sofosbuvir/velpatasvir; sustained virological response.

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Conflict of interest statement

Alessandra Mangia: Research grants from Gilead Sciences, Merck Sharp and Dohme, Janssen and Bristol‐Myers Squibb. Part of the speaker bureau for Gilead Sciences, Intercept and Merck Sharp and Dohme. Scott Milligan: Research support from Gilead Sciences, during the conduct of the study. Research support from Gilead Sciences, AbbVie and Merck Sharp and Dohme, outside the submitted work. Mandana Khalili: Grants from HCV‐TARGET study sponsors, during the conduct of the study. HCV‐TARGET is an investigator‐initiated study jointly sponsored by The University of Florida, Gainesville, FL (PI: Nelson), and The University of North Carolina at Chapel Hill, Chapel Hill, NC (PI: Fried) and is funded in part by AbbVie, Bristol Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Kadmon, and Merck. Grants from Gilead Sciences, Intercept Pharmaceuticals and AbbVie, outside of submitted work. Personal fees from Gilead Sciences, outside the submitted work. Stefano Fagiuoli: Grants and personal fees from Gilead Sciences, AbbVie and Novartis, outside the submitted work. Personal fees from Merck Sharp and Dohme, Astellas and Bayer, outside the submitted work. Stephen Shafran: Grants and personal fees from Gilead Sciences, during the conduct of the study. Grants from AbbVie, Merck Sharp and Dohme, and Janssen, outside the submitted work. Fabrice Carrat; Grants from Inserm‐ANRS, during the conduct of the study. Denis Ouzan: Grants from Gilead Sciences, during the conduct of the study. Grants, personal fees and non‐financial support from Gilead Sciences and AbbVie, outside the submitted work. George Papatheodoridis: Grants from Gilead Sciences, during the conduct of the study. Grants from Gilead Sciences and AbbVie, outside of submitted work. Personal fees and non‐financial support from Gilead Sciences, AbbVie and Merck Sharp and Dohme, outside of submitted work. Alnoor Ramji: Grants from AbbVie, Gilead Sciences, Janssen, Novartis, Merck and Springbanks, outside the submitted work. Other from AbbVie, Allergen, Assembly, Celgene, Gilead Sciences and Janssen. Sergio Borgia: Nothing to disclose. Heiner Wedemeyer: Grants and personal fees from Gilead Sciences, during the conduct of the study. Grants, personal fees and non‐financial support from Abbott and Roche Diagnostics, outside the submitted work. Grants and personal fees from Bristol Myers Squibb, Novartis, Roche Diagnostics, Merck Sharp and Dohme, Eiger and Falk and Falk Foundation, outside the submitted work. Personal fees from Siemens and Janssen, outside the submitted work. Investigator for Transgene, outside the submitted work. Non‐financial support from MYR‐GmbH, outside the submitted work. Ruggero Losappio: Nothing to disclose. Francisco Pérez‐Hernandez: Personal fees from Gilead Sciences and AbbVie, outside the submitted work. Nicole Wick: Research support from Gilead Sciences, during the conduct of the study. Research support from AbbVie and Merck, outside the submitted work. Robert S Brown Jr: Grants and personal fees from Gilead Sciences, during the conduct of the study. Grants and personal fees from AbbVie, outside of submitted work. Pietro Lampertico: Personal fees from Gilead Sciences, AbbVie and Merck Sharp and Dohme, outside the submitted work. Karen Doucette: Clinical trials and honoraria from Gilead Sciences and unrestricted educational grant from Merck, outside the submitted work. Ioanna Ntalla, Heribert Ramroth, Michael Mertens and Kim Vanstraelen: Employees and stock owners of Gilead Sciences, during the conduct of the study and outside of submitted work. Juan Turnes: Personal fees from AbbVie, outside the submitted work. Personal fees and grant from Gilead Sciences, outside the submitted work.

Figures

Figure 1
Figure 1
Flowchart and response of patients included in the real‐world effectiveness analysis. †Overall population includes all patients who achieved SVR12/24, and those who did not achieve SVR12/24 due to virological and non‐virological reasons and patients for which the reason for achieving SVR12/24 was unknown. ‡Effectiveness population includes all patients who achieved SVR12/24 and those who did not achieve SVR12/24 due to virological reasons. §Two patients died due to sepsis, one due to cancer (not specified further), one due to haemoptysis secondary to primary lung cancer, cause of death was not specified for 13 patients. 32 patients relapsed, 11 were non‐responders, three were breakthroughs; details of the virological reason were not specified for nine patients, as evaluated and documented by the treating physician. LFTU, lost to follow‐up; SVR12/24, sustained virological response 12/24 weeks after end of treatment
Figure 2
Figure 2
SVR12/24 in the effectiveness population analysis. Percentage of patients achieving SVR12/24 in the effectiveness population after being treated with SOF/VEL for 12 weeks without ribavirin, stratified by (A) HCV genotype (B) fibrosis stage (C) intravenous drug use, PPI use at baseline and treatment history. †The definition of former drug use varied between cohorts with respect to timing and this level of detail was not available for most patients. ‡Information on patients achieving SVR12/24 by PPI use at baseline was not available in one cohort, and thus patients from this cohort (n = 183) were not considered in this subgroup analysis. §Patients were treated with PEG‐IFN + RBV (± PI boceprevir, telaprevir, simeprevir). F, fibrosis; GT, genotype; PEG‐IFN, pegylated interferon; PI, protease inhibitor; PPI, proton pump inhibitor; RBV, ribavirin; SOF/VEL, sofosbuvir/velpatasvir; SVR12/24, sustained virological response 12/24 weeks after the end of treatment
Figure 3
Figure 3
SVR12/24 outcomes in the overall patient population. Treatment outcomes in the overall patient population treated with SOF/VEL for 12 weeks without RBV. †Other non‐virological reasons were: death (5.1%; 17/332), consent withdrawal (0.3%; 1/552), non‐adherence (0.6%; 2/332) and reinfection (0.6%; 2/332). LFTU, lost to follow‐up; RBV, ribavirin; SOF/VEL, sofosbuvir/velpatasvir; SVR12/24, sustained virological response 12/24 weeks after the end of t`reatment
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