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

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 nonvirological reasons (67% lost to follow-up; 26.5% early treatment discontinuation). This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Letter: now is the time to remove complexity from HCV guidelines to ensure that elimination remains a priority

“…Conversely, despite consistently high cure rates with SOF/VEL for 12 weeks in diverse populations, including patients with baseline RAS, RAS testing is recommended before starting SOF/VEL in GT3 patients with compensated cirrhosis. 8,9 We agree with Kwong that, given the high cure rates achieved with pangenotypic therapies and the low prevalence of RAS, simplified HCV management should be prioritised to enable HCV elimination and that introducing RAS testing for GLE/PIB would complicate treatment in GT3 patients. 2…”

“…5 In contrast, high cure rates have been demonstrated with sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks in over 330 GT3 patients with compensated cirrhosis in clinical studies and supported by extensive real-world experience, including in patients with advanced cirrhosis and portal hypertension ( Table 1). [6][7][8][9] Recently, 97% of the 324 cirrhotic GT3 patients in a global cohort were cured, irrespective of RAS testing. 9 GLE/PIB is currently recommended for GT3 patients by international guidelines, 3,10 including for those with compensated cirrhosis, without the need for baseline RAS testing; a recommendation based on the low patient numbers included in trials.…”

“…[6][7][8][9] Recently, 97% of the 324 cirrhotic GT3 patients in a global cohort were cured, irrespective of RAS testing. 9 GLE/PIB is currently recommended for GT3 patients by international guidelines, 3,10 including for those with compensated cirrhosis, without the need for baseline RAS testing; a recommendation based on the low patient numbers included in trials. Conversely, despite consistently high cure rates with SOF/VEL for 12 weeks in diverse populations, including patients with baseline RAS, RAS testing is recommended before starting SOF/VEL in GT3 patients with compensated cirrhosis.…”

“…Response to SOF/VEL for 12 weeks in GT3 patients with compensated cirrhosis (treatment-naïve or peginterferon + ribavirin experienced) [6][7][8][9]…”

Letter: now is the time to remove complexity from HCV guidelines to ensure that elimination remains a priority—authors' reply

“…In a recent real‐world study, all patients with HCV infection were provided sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks. In patients with genotype 3 infection and compensated cirrhosis, 314 of 324 (96.9%) achieved remission with SOF/VEL 6 . Considering the impact of this regimen, pan‐genotypic coverage of the drug, and the impact these medications can have in the low‐income parts of the world, baseline RAS testing seems to be redundant.…”