Dataset Information

Real-World Effectiveness of Simeprevir-containing Regimens Among Patients With Chronic Hepatitis C Virus: The SONET Study.

ABSTRACT: BACKGROUND:The Simeprevir ObservatioNal Effectiveness across practice seTtings (SONET) study evaluated the real-world effectiveness of simeprevir-based treatment for hepatitis C virus (HCV) infection. METHODS:The SONET study was a phase 4, prospective, observational, United States-based study enrolling patients ?18 years of age with chronic genotype 1 HCV infection. The primary endpoint was the proportion of patients who achieved sustained virologic response 12 weeks after the end of treatment (SVR12), defined as HCV ribonucleic acid undetectable ?12 weeks after the end of all HCV treatments. RESULTS:Of 315 patients (intent-to-treat [ITT] population), 275 (87.3%) completed the study. Overall, 291 were treated with simeprevir + sofosbuvir, 17 with simeprevir + sofosbuvir + ribavirin, and 7 with simeprevir + peginterferon + ribavirin. The majority of patients were male (63.2%) and white (60.6%); median age was 58 years, 71.7% had genotype/subtype 1a, and 39.4% had cirrhosis. The SVR12 was achieved by 81.2% (255 of 314) of ITT patients (analysis excluded 1 patient who completed the study but was missing SVR12 data); 2 had viral breakthrough and 18 had viral relapse. The SVR12 was achieved by 92.4% (255 of 276) of patients in the modified ITT (mITT) population, which excluded patients who discontinued treatment for nonvirologic reasons before the SVR12 time point or were missing SVR12 assessment data. Among mITT patients, higher SVR12 rates were associated with factors including age ?65 years, non-Hispanic/Latino ethnicity, and employment status, but not genotype/subtype nor presence of cirrhosis. Simeprevir-based treatment was well tolerated; no serious adverse events were considered related to simeprevir. CONCLUSIONS:In the real-world setting, simeprevir + sofosbuvir treatment was common and 92% of mITT patients achieved SVR12. Simeprevir-based treatment was effective and well tolerated in this cohort, including patients with cirrhosis.

SUBMITTER: Alam I

PROVIDER: S-EPMC5413999 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Real-World Effectiveness of Simeprevir-containing Regimens Among Patients With Chronic Hepatitis C Virus: The SONET Study.

Alam Imtiaz I Brown Kimberley K Donovan Cynthia C Forlenza Jamie J Lauwers Kris K Mah'moud Mitchell A MA Manch Richard R Mohanty Smruti R SR Prabhakar Avinash A Reindollar Robert R DeMasi Ralph R Slim Jihad J Tandon Neeta N Villadiego Shirley S Naggie Susanna S

Open forum infectious diseases 20161226 1

<h4>Background</h4>The Simeprevir ObservatioNal Effectiveness across practice seTtings (SONET) study evaluated the real-world effectiveness of simeprevir-based treatment for hepatitis C virus (HCV) infection.<h4>Methods</h4>The SONET study was a phase 4, prospective, observational, United States-based study enrolling patients ≥18 years of age with chronic genotype 1 HCV infection. The primary endpoint was the proportion of patients who achieved sustained virologic response 12 weeks after the end ...[more]

PMID: 28480251

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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:The combination of the direct-acting antivirals, simeprevir (SMV) and sofosbuvir (SOF), was the first highly efficacious interferon-free combination for treating patients with hepatitis C virus (HCV), and was widely used in Italy as a result.The aim of this study was to evaluate effectiveness and safety of SMV in Italian patients with HCV genotype (GT) 1 and 4 overall, by treatment regimen [SMV/SOF and SMV/SOF+ribavirin (RBV)], cirrhosis status, and GT (GT1a, GT1b, and GT4).An observational multicenter cohort study was conducted in 46 centers across Italy. Adult HCV + GT1 or GT4 patients, naive or treatment-experienced, with or without cirrhosis, who underwent treatment with a SMV-containing regimen from May to September 2015 were included. The primary endpoint was sustained virologic response (SVR), defined as undetectable serum HCV RNA levels 12 weeks after treatment end (SVR12). The secondary endpoints included duration of treatment, safety and tolerability of each treatment regimen, and SVR by treatment and according to response to previous treatment and fibrosis stage. The association between SVR and a subset of the most clinically relevant variables was investigated by a multivariate logistic regression analysis.A total of 349 HCV-positive patients treated with an SMV-based regimen were enrolled, of whom 342 received SMV/SOF?±?RBV and were included in this analysis. Most patients (59.4%) were treatment-experienced and had cirrhosis (78.1%). In the group receiving SMV/SOF?+?RBV, most (63.1%) were treatment-experienced and 82.9% had cirrhosis. Three patients were lost to follow-up; 330 patients receiving SMV/SOF?±?RBV (96.5%) were treated for 12 weeks. Overall, SVR12 was achieved by 324 patients [94.2%, 95% confidence interval (95% CI) 92-97]. When stratified by treatment and clinical and virologic characteristics, SVR12 was achieved by 77 of 79 [97.5% (95% CI 94.0-100.0)] and 247 of 263 [93.9% (95% CI 91.0-96.8)] patients receiving SMV/SOF and SMV/SOF?+?RBV, respectively; 132 of 139 (95.0%) naive versus 192/203 (94.6%) treatment-experienced patients; 250 of 267 (93.6%) cirrhotic and 56 of 62 (90.3%) HIV coinfected patients. SMV-based regimens were generally well tolerated. Adverse events leading to treatment discontinuations were not observed.A high proportion of patients treated with SMV/SOF-based regimens achieved SVR12 in this study. A high SVR12 rate was also achieved in patients with cirrhosis, treatment experience, and HUV coinfected patients.

Project description:BACKGROUND & AIMS:The interferon-free regimen of simeprevir plus sofosbuvir was recommended by professional guidelines for certain patients with hepatitis C virus (HCV) genotype 1 infection based on the findings of a phase 2 trial. We aimed to evaluate the safety and efficacy of this regimen in clinical practice settings in North America. METHODS:We collected demographic, clinical, and virologic data, as well as reports of adverse outcomes, from sequential participants in HCV-TARGET--a prospective observational cohort study of patients undergoing HCV treatment in routine clinical care settings. From January through October 2014, there were 836 patients with HCV genotype 1 infection who began 12 weeks of treatment with simeprevir plus sofosbuvir (treatment duration of up to 16 weeks); 169 of these patients received ribavirin. Most patients were male (61%), Caucasian (76%), or black (13%); 59% had cirrhosis. Most patients had failed prior treatment with peginterferon and ribavirin without (46%) or with telaprevir or boceprevir (12%). The primary outcome was sustained virologic response (SVR), defined as the level of HCV RNA below quantification at least 64 days after the end of treatment (beginning of week 12 after treatment--a 2-week window). Logistic regression models with inverse probability weights were constructed to adjust for baseline covariates and potential selection bias. RESULTS:The overall SVR rate was 84% (675 of 802 patients, 95% confidence interval, 81%-87%). Model-adjusted estimates indicate patients with cirrhosis, prior decompensation, and previous protease inhibitor treatments were less likely to achieve an SVR. The addition of ribavirin had no detectable effects on SVR. The most common adverse events were fatigue, headache, nausea, rash, and insomnia. Serious adverse events and treatment discontinuation occurred in only 5% and 3% of participants, respectively. CONCLUSIONS:In a large prospective observational cohort study, a 12-week regimen of simeprevir plus sofosbuvir was associated with high rates of SVR and infrequent treatment discontinuation. ClinicalTrials.gov: NCT01474811.

Project description:Persons with hepatitis C virus (HCV) genotype 1a (GT1a) infections harboring a baseline Q80K polymorphism in nonstructural protein 3 (NS3) have a reduced virologic response to simeprevir in combination with pegylated interferon-alfa and ribavirin. We aimed to develop, validate, and freely disseminate an NS3 clinical sequencing assay to detect the Q80K polymorphism and potentially other HCV NS3 drug resistance mutations. HCV RNA was extracted from frozen plasma using a NucliSENS easyMAG automated nucleic acid extractor, amplified by nested reverse transcription-PCR, and sequenced using Sanger and/or next-generation (MiSeq) methods. Sanger chromatograms were analyzed using in-house software (RECall), and nucleotide mixtures were called automatically. MiSeq reads were iteratively mapped to the H77 reference genome, and consensus NS3 sequences were generated with nucleotides present at >20% called as mixtures. The accuracy, precision, and sensitivity for detecting the Q80K polymorphism were assessed in 70 samples previously sequenced by an external laboratory. A comparison of the sequences generated by the Sanger and MiSeq methods with those determined by an external lab revealed >98.5% nucleotide sequence concordance and zero discordant calls of the Q80K polymorphism. The results were both highly repeatable and reproducible (>99.7% nucleotide concordance and 100% Q80K concordance). The limits of detection (>2 and ∼5 log10 IU/ml for the Sanger and MiSeq assays, respectively) are sufficiently low to allow genotyping in nearly all chronically infected treatment-naive persons. No systematic bias in the under- or overamplification of minority variants was observed. Coinfection with other viruses (e.g., HIV and hepatitis B virus [HBV]) did not affect the assay results. The two independent HCV NS3 sequencing assays with the automated analysis procedures described here are useful tools to screen for the Q80K polymorphism and other HCV protease inhibitor drug resistance mutations.

Project description:Patients' experience during treatment may affect treatment adherence. Our aim was to assess the impact of patient-reported outcomes (PROs) on adherence to different anti-hepatitis C virus (HCV) regimens.Clinical, demographic, and PRO data (short form-36 [SF-36], chronic liver disease questionnaire-hepatitis C version [CLDQ-HCV], functional assessment of chronic illness therapy-fatigue [FACIT-F], work productivity and activity impairment: specific health problem [WPAI:SHP]) from 13 multinational clinical trials of anti-HCV treatment were available. Treatment adherence was defined as >80% of prescribed doses taken.Included were 4825 HCV patients. Regimens were grouped into: interferon- and ribavirin (RBV)-containing (±sofosbuvir [SOF]), interferon-free RBV-containing (RBV?+?SOF?±?ledipasvir [LDV]), and interferon-free RBV-free (LDV/SOF). The adherence to these regimens were 77.6%, 84.3%, and 96.2%, respectively (P?<?0.0001). Nonadherent patients were more likely to be unemployed and to have a greater PRO impairment at baseline (up to -5.3% lower PRO scores, P?<?0.0001). During treatment with interferon- or RBV-based regimens, nonadherent patients experienced lower PROs and had larger decrements from their baseline PRO scores. In contrast, there were no significant declines in PRO scores (all P?>?0.05) for the small number of patients who were nonadherent to LDV/SOF. In multivariate analysis, being treatment-naive, longer treatment duration, and receiving an interferon- or RBV-containing regimen were associated with a lower likelihood of adherence (all P?<?0.003). Better baseline and on-treatment PRO scores were associated with a higher likelihood of adherence to interferon and RBV.The use of interferon and/or RBV, longer duration of treatment, and lower baseline and on-treatment PRO scores were linked to a decreased likelihood of being adherent to interferon?+?RBV-containing or interferon-free RBV-containing antiviral regimens. Interferon- and RBV-free regimens were associated with excellent adherence.

Dataset Information

Real-World Effectiveness of Simeprevir-containing Regimens Among Patients With Chronic Hepatitis C Virus: The SONET Study.

Publications

Real-World Effectiveness of Simeprevir-containing Regimens Among Patients With Chronic Hepatitis C Virus: The SONET Study.

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