Dataset Information

Real-world Effectiveness of Sofosbuvir/Velpatasvir for Treatment of Chronic Hepatitis C in British Columbia, Canada: A Population-Based Cohort Study.

ABSTRACT: Background:Clinical trials show high efficacy of sofosbuvir/velpatasvir (SOF/VEL), but there are limited data from "real-world" settings. We aimed to evaluate SOF/VEL effectiveness for all hepatitis C virus (HCV) genotypes (GTs) in British Columbia (BC), Canada. Methods:We used the BC Hepatitis Testers Cohort, which includes all HCV cases in the province (1990-2015) linked to administrative databases, including prescriptions to end of 2018. We measured sustained virologic response (SVR; negative RNA??10 weeks after treatment end) and identified characteristics associated with non-SVR. Conservatively, we excluded individuals with no assessment for SVR if their last RNA test after treatment initiation was negative (but included if positive). Results:Of 2821 eligible participants, most were infected with GT1 (1076, 38.1%) or GT3 (1072, 38.0%), and a minority (278, 9.9%) were treated with RBV. SVR was 94.6% (2670/2821) overall and 94.5% (1017/1076) for GT1, 96.4% (512/531) for GT2, and 93.7% (1004/1072) for GT3. When disaggregated by GT, treatment regimen, and cirrhosis/treatment experience, SVR was lowest (30/40, 75.0%) among treatment-experienced GT3 individuals treated with RBV. Characteristics associated with non-SVR in multivariable analysis included younger age, RBV addition, and being a person with HIV (PWH) or who injects/injected drugs (PWID). When treatment regimen (±RBV) was removed from multivariable model, treatment experience was associated with non-SVR for GT3. Of 151 non-SVR individuals, 56.3% were nonvirological failures (treatment incomplete/no assessment for SVR) and 43.7% were virological failures (nonresponse/relapse). A disproportionately high percentage of non-SVR among PWID was due to nonvirological failure. Conclusions:SOF/VEL was highly effective in this "real-world" population-based cohort. Additional support is required for PWID/PWH to reach SVR.

SUBMITTER: Wilton J

PROVIDER: S-EPMC7052750 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Real-world Effectiveness of Sofosbuvir/Velpatasvir for Treatment of Chronic Hepatitis C in British Columbia, Canada: A Population-Based Cohort Study.

Wilton James J Wong Stanley S Yu Amanda A Ramji Alnoor A Cook Darrel D Butt Zahid A ZA Alvarez Maria M Binka Mawuena M Darvishian Maryam M Jeong Dahn D Bartlett Sofia R SR Pearce Margo E ME Adu Prince A PA Yoshida Eric M EM Krajden Mel M Janjua Naveed Z NZ

Open forum infectious diseases 20200229 3

<h4>Background</h4>Clinical trials show high efficacy of sofosbuvir/velpatasvir (SOF/VEL), but there are limited data from "real-world" settings. We aimed to evaluate SOF/VEL effectiveness for all hepatitis C virus (HCV) genotypes (GTs) in British Columbia (BC), Canada.<h4>Methods</h4>We used the BC Hepatitis Testers Cohort, which includes all HCV cases in the province (1990-2015) linked to administrative databases, including prescriptions to end of 2018. We measured sustained virologic response ...[more]

PMID: 32154326

Similar Datasets

Project description:Background & aimsVoxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) is highly effective for re-treatment of direct-acting antiviral (DAA)-experienced patients with chronic HCV infection. In the present study, predictors of virologic treatment response were analyzed in an integrative analysis of three large real-world cohorts.MethodsConsecutive patients re-treated with VOX/VEL/SOF after DAA failure were enrolled between 2016 and 2021 in Austria, Belgium, Germany, Italy, Spain and Switzerland.ResultsA total of 746 patients were included: median age was 56 (16-88) years and 77% were male. Most patients were infected with HCV genotype 1 (56%) and 3 (32%). 86% of patients carried resistance-associated substitutions in the NS3, NS5A or NS5B regions. Overall, 95.4% (683/716) of patients achieved a sustained virologic response. Treatment effectiveness was significantly affected by advanced liver disease (p <0.001), hepatocellular carcinoma (p <0.001), higher baseline ALT levels (p = 0.02), HCV genotype 3 (p <0.001), and prior VEL/SOF treatment (p = 0.01). In a multivariate analysis, only HCV genotype 3, hepatocellular carcinoma and cirrhosis turned out to be independent predictors of treatment failure. Resistance-associated substitutions, as well as the presence of rare genotypes, did not impact treatment outcome. The effectiveness of rescue therapy with glecaprevir/pibrentasvir and SOF, with or without ribavirin, for 12 to 24 weeks was found to be high (100%).ConclusionsInfection with HCV genotype 3, the presence of liver cancer and cirrhosis are independently associated with failure of VOX/VEL/SOF re-treatment. It is unclear whether the addition of ribavirin and/or extension of treatment duration may be effective to avoid virologic relapse on VOX/VEL/SOF. However, rescue treatment with glecaprevir/pibrentasvir+SOF seems to be effective.Impact and implicationsRepresentative data on the effectiveness of voxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) in clinical practice are still scarce and the collection of a larger number of patients with difficult-to-treat cofactors including the assessment of resistance-associated substitution profiles is required before more specific recommendations for optimal re-treatment in these patients can be given. Thus, we aimed to analyze treatment effectiveness and predictors of virologic response to VOX/VEL/SOF in an integrative analysis of three large real-word cohorts. The study results, derived from a multicenter cohort consisting of 746 patients, demonstrated that re-treatment with VOX/VEL/SOF is an effective salvage therapy associated with an overall per protocol sustained virologic response rate of 95%. Hepatocellular carcinoma onset, cirrhosis and HCV genotype 3 were identified as independent negative predictors of treatment response, whereas resistance-associated substitutions, as well as rare genotypes and chimera, did not impact sustained virologic response rates following re-treatment with VOX/VEL/SOF.

Project description:IntroductionPangenotypic direct-acting antivirals are expected to cure hepatitis C virus (HCV) in more than 95% of treated patients. However, data on the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) in Taiwan are limited. This study aims to characterize the patient population in the nationwide Taiwan Association for the Study of the Liver (TASL) HCV Registry and evaluate treatment outcome in Taiwanese patients receiving SOF/VEL.MethodsThis study was a retrospective-prospective, observational, multicenter, real-world analysis. Adults with chronic hepatitis C were treated with SOF/VEL 400/100 mg ± ribavirin for 12 weeks. The primary outcome was sustained virologic response 12 weeks after end of therapy (SVR12). Factors associated with not achieving SVR12 were evaluated using logistic regression and covariate analysis. Safety was also assessed.ResultsIn total, 3480 patients were included: 86.8% genotype 1/2, 2.8% genotype 3, 0.1% genotype 4/5, 9.6% genotype 6; unclassified, 0.8%; 12.2% compensated cirrhosis; 3.3% decompensated cirrhosis; and 15.8% chronic kidney disease. Overall SVR12 rate was 99.4% (genotype 1, 99.5%; genotype 2, 99.4%; genotype 3, 96.9%; genotype 4, 100%; genotype 6, 99.7%). SVR12 rates among patients with compensated cirrhosis, decompensated cirrhosis, and chronic kidney disease stages 4-5 were 99.5%, 100%, and 100%, respectively. There were 21 patients (0.6%) who did not achieve SVR12. Factors associated with failure were treatment adherence below 60%, high viral load, and genotype 3 (p < 0.001, p = 0.028, and p = 0.001, respectively). Adverse events occurred in 10% of patients; 0.6% were serious and one was related to treatment. Treatment discontinuation occurred in 0.3% of patients; none were treatment related. The estimated glomerular filtration rate remained stable throughout treatment and follow-up, regardless of baseline values and cirrhosis status.ConclusionSOF/VEL was highly effective and well tolerated in Taiwanese patients, irrespective of viral genotype, liver disease severity, and comorbidities.

Project description:BACKGROUND:Hepatitis C virus (HCV) genotype 6 is the commonest cause of chronic hepatitis C infection in much of southeast Asia, but data on the effectiveness of direct-acting antiviral agents (DAAs) against this genotype are limited. We conducted a retrospective cohort study of patients attending the Hospital for Tropical Diseases (HTD), Ho Chi Minh City, Vietnam, to define the effectiveness of DAAs in the treatment of chronic HCV genotype 6 in actual practice. METHODS:We included all patients with genotype 6 infections attending our hospital between March 2016 and October 2017 who received treatment with sofosbuvir-based DAA treatment regimens, and compared their responses with those with genotype 1 infections. RESULTS:1758 patients (1148 genotype 6, 65.4%; 610 genotype 1, 34.6%) were analyzed. The majority of patients (1480, 84.2%) received sofosbuvir/ledipasvir (SOF/LDV) ± ribavirin (RBV); 278 (15.8%) received sofosbuvir/Daclatasvir (SOF/DCV) ± RBV. The median age of the patients was 57 years, (interquartile range (IQR) 46-64 years) The baseline HCV viral load (log IU/ml) was significantly higher in patients infected with genotype 6 compared with those infected with genotype 1 (6.8, 5.3-6.6 versus 6.3, 5.3-6.5 log10 IU/ml, p = <0.001, Mann Whitney U test). A sustained virological response (SVR), defined as an undetectable viral load measured between 12 and 24 weeks after completing treatment, and indicating cure, was seen in 97.3% (1711/1758) of patients. Treatment failure, defined as HCV viral load ?15 IU/ml ?12 weeks after completing treatment appeared to be more frequent in patients infected with genotype 6 virus (3.2%, 37/1148) than in those infected with genotype 1 (1.7%, 10/610), p = 0.050 chi-squared test). We found no evidence that patient's age, gender, liver cirrhosis, diabetes, HBV or HIV coinfection, prior treatment failure with pegylated interferon therapy, body mass index (BMI), aspartate aminotransferase to platelet ratio index (APRI), or fibrosis 4 (FIB-4) index were associated with treatment failure. CONCLUSIONS:Our study suggests that patients with HCV genotype 6 infection in Vietnam may respond less well to treatment with sofosbuvir based DAAs than patients with genotype 1 infections. Further studies are needed to confirm this observation and to define whether it is driven by genotype-specific mutations.

Project description:IntroductionReal-world data regarding the impact of hepatic fibrosis on the effectiveness of sofosbuvir/velpatasvir (SOF/VEL) treatment is limited in the Asian population.MethodsWe analyzed data for all 823 patients with hepatitis C virus treated with SOF/VEL from June 2019 to September 2020 at Chang Gung Memorial Hospital in Chiayi, Taiwan. The degree of fibrosis was determined using the fibrosis-4 (FIB-4) index, with advanced fibrosis or cirrhosis defined as a FIB-4 score of > 3.25. The primary treatment outcome was the rate of sustained virologic response 12 weeks after treatment cessation (SVR). Adverse events (AEs) were also evaluated.ResultsSVR rates did not significantly differ (p > 0.05) between patients with FIB-4 scores of ≤ 3.25 and those with scores of > 3.25. In the per protocol analysis, 99.2% (593/598) of the FIB-4 ≤ 3.25 group and 100% (172/172) of the FIB-4 > 3.25 group achieved SVR; in the evaluable population analysis, 93.4% (593/635) of the FIB-4 ≤ 3.25 group and 91.5% (172/188) of the FIB-4 > 3.25 group achieved SVR. Five patients with FIB-4 scores of ≤ 3.25 did not attain SVR: two relapsed and three had no response. The most common AEs were comparable (p > 0.05) for the FIB-4 ≤ 3.25 group and the FIB-4 > 3.25 group and included abdominal discomfort (4.4% vs. 5.9%), fatigue (4.1% vs. 5.9%), and skin itching (3.6% vs. 3.2%). Laboratory abnormalities were more common in the FIB-4 > 3.25 group (p < 0.001). Six patients with FIB-4 scores of > 3.25 had total bilirubin elevation > 3 × the upper normal limit (UNL). Alanine transaminase elevation > 5 × the UNL was observed in two patients with FIB-4 scores of ≤ 3.25 and one patient with a FIB-4 score of > 3.25. No AEs resulted in treatment discontinuation.ConclusionsSOF/VEL treatment is well tolerated and achieves high SVR rates for patients of Taiwanese ethnicity with HCV, regardless of cirrhosis status.

Project description:BackgroundCetuximab and panitumumab, two anti-EGFR therapies, are widely used for third-line therapy of metastatic colorectal cancer (mCRC) with wild-type KRAS, but there remains uncertainty around their cost effectiveness. The objective of this analysis was to conduct a real-world cost-effectiveness analysis of the policy change introducing KRAS testing and third-line anti-EGFR therapy mCRC in British Columbia (BC), Canada.MethodsWe conducted secondary analysis of administrative data for a cohort of mCRC patients treated in BC in 2006-2015. Patients potentially eligible for KRAS testing and third-line therapy after the policy change (July 2009) were matched 2:1 to pre-policy patients using genetic matching on propensity score and baseline covariates. Costs and survival time were calculated over an 8-year time horizon, with bootstrapping to characterize uncertainty around endpoints. Cost effectiveness was expressed using incremental cost-effectiveness ratios (ICER) and the probability of cost effectiveness at a range of thresholds.ResultsThe cohort included 1757 mCRC patients (n = 456 pre-policy and n = 1304 post-policy; of those, n = 420 received cetuximab or panitumumab). There was a significant increase in survival and cost following the policy change. Adoption of KRAS testing and anti-EGFR therapy had an ICER of CA$73,759 per life-year gained (LYG) (95% CI 46,133-186,446). In scenario analysis, a reduction in cetuximab and panitumumab cost of at least 50% was required to make the policy change cost effective at a threshold of CA$50,000/LYG.ConclusionA policy of third-line anti-EGFR therapy informed by KRAS testing may be considered cost effective at thresholds above CA$70,000/LYG. Reduction in drug costs, through price discounts or potential future biosimilars, would make anti-EGFR therapy considerably more cost effective. By using real-world data for a large cohort with long follow-up we can assess the value of a policy of KRAS testing and anti-EGFR therapy achieved in practice.

Project description:BackgroundPeople undergoing chronic dialysis are at an increased risk of active tuberculosis (TB). In 2012, the Canadian province of British Columbia began systematically screening people initiating dialysis for latent TB using interferon-gamma release assay (IGRA), and treating when appropriate.ObjectiveThe objective of this study was to compare active TB rate in people who initiated dialysis and were screened using an IGRA compared with those not screened during the same period.DesignRetrospective cohort study.SettingBritish Columbia (BC), a Canadian province of 5.0 million people with an active TB incidence of 5.1 per 100 000 population.ParticipantsAll people in BC who initiated at least 90 days of dialysis between January 2012 and May 2017 were included in the study. People were excluded if they were <18 years of age or had a prior history of active TB diagnosis or treatment for latent TB.MethodsA retrospective cohort was created of British Columbians who initiated dialysis between 2012 and 2017. Individuals were stratified into a screened and nonscreened group. Multivariable Cox regression was used to determine the association between latent TB screening and the development of active TB. The primary outcome was incident active TB, either microbiologically confirmed or clinically diagnosed.ResultsOf the 3190 people included in the study, 1790 (56.1%) were screened, of which 152 (8.5%) initiated latent TB treatment postscreening. During follow-up, incident active TB was diagnosed in 6 (0.3%) of the 1790 people screened, compared with 11 (0.8%) of the 1400 people who received no screening. In multivariable analysis, latent TB screening and treatment was associated with a significant reduction in the rate of active TB (adjusted hazard ratio = 0.3, 95% confidence interval = 0.1-0.8; P < .01).LimitationsThis was an observational retrospective study and the potential for unmeasured confounding should be carefully assessed.ConclusionsThese findings suggest that systematically screening and treating people initiating dialysis can significantly decrease the rate of active TB in this high-risk population. Given the importance of screening high-risk groups, the results from this analysis could inform scale-up of TB screening in dialysis programs in other low incidence regions. Trial registration is not applicable as this was a retrospective cohort analysis and not a randomized trial.

Dataset Information

Real-world Effectiveness of Sofosbuvir/Velpatasvir for Treatment of Chronic Hepatitis C in British Columbia, Canada: A Population-Based Cohort Study.

Publications

Real-world Effectiveness of Sofosbuvir/Velpatasvir for Treatment of Chronic Hepatitis C in British Columbia, Canada: A Population-Based Cohort Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets