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Acta Bio-medica : Atenei Parmensis May 2019In literature systematic data on treatment with the fixed-dose combination of sofosbuvir and velpatasvir for 12 weeks in anti-HCV/HCV RNA positive subjects with mild... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
In literature systematic data on treatment with the fixed-dose combination of sofosbuvir and velpatasvir for 12 weeks in anti-HCV/HCV RNA positive subjects with mild fibrosis and naïve to previous Interferon free regimen are scanty. A meta-analysis has been performed to evaluate the efficacy of velpatasvir plus sofosbuvir combination in these patients.
METHODS
All randomized or non-randomized studies, investigating the sustained virological response rate to sofosbuvir plus velpatasvir without ribavirin for 12 weeks in subjects naïve to previous DAA therapy and with fibrosis F0-F2 or F0-F3, were included in the meta-analysis.
RESULTS
A total of 16 studies enrolling 4,907 subjects met the inclusion criteria and were included in this meta-analysis. The prevalence of SVR by sofosbuvir and velpatasvir was 98% (95% CI 96-99%) in the 4,907 subjects without cirrhosis. The prevalence of SVR was similar considering the 9 clinical studies and the 7 real-world studies (98%, CI 95%: 96-99% and 98%; CI 95%: 96-99%, respectively). Considering the 4 studies enrolling 1,371 subjects without advanced liver fibrosis the prevalence of SVR was also high [96% (95% CI: 94-98%)]. Data indicate a prevalence of SVR ranging to 95-100% according to the different HCV genotypes.
CONCLUSION
Sofosbuvir plus velpatasvir therapeutic regimen was highly effective in HCV patients without advanced liver disease naïve to previous DAA regimen independently the different HCV genotypes.
Topics: Antiviral Agents; Carbamates; Controlled Clinical Trials as Topic; Drug Administration Schedule; Drug Combinations; Female; Hepacivirus; Heterocyclic Compounds, 4 or More Rings; Humans; Liver Cirrhosis; Male; Prognosis; Randomized Controlled Trials as Topic; Severity of Illness Index; Sofosbuvir; Sustained Virologic Response; Treatment Outcome
PubMed: 31124995
DOI: 10.23750/abm.v90i2.8374 -
International Journal of Infectious... Jun 2019With the appearance of direct-acting antiviral agents (DAAs), sofosbuvir (SOF)-based DAAs are recommended for patients with hepatitis C virus (HCV) recurrence after... (Meta-Analysis)
Meta-Analysis
A systematic review with meta-analysis: Is ribavirin necessary in sofosbuvir-based direct-acting antiviral therapies for patients with HCV recurrence after liver transplantation?
OBJECTIVES
With the appearance of direct-acting antiviral agents (DAAs), sofosbuvir (SOF)-based DAAs are recommended for patients with hepatitis C virus (HCV) recurrence after liver transplantation (LT). Whether ribavirin (RBV) is needed by patients after LT in combination with SOF-based DAAs remains to be determined. This meta-analysis was conducted to evaluate the necessity of RBV with SOF-based DAAs for post-LT patients.
METHODS
PubMed, Web of Science, Cochrane Library and EMBASE databases were systematically searched for eligible studies from the databases' inceptions until November 2018. We accepted the studies that included HCV recurrence in post-LT patients who were treated with SOF-based DAAs ± RBV, and evaluated the rate of sustained virological response 12 weeks (SVR12) after the end of treatment.
RESULTS
Twelve studies, comprising a total of 1466 LT recipients, were included in this study. The pooled SVR12 of these patients was 91% (95% CI: 84% to 95%). There was no statistical difference of SVR12 in the patients treated with SOF-based DAAs + RBV versus -RBV group (risk ratio [RR] = 0.97; 95% CI: 0.92 to 1.03; P = 0.35) by different therapy duration (P = 0.26), with different targets of DAAs (P = 0.13) and in different regions (P = 0.34) but a tendency for a higher incidence of anemia in the +RBV group than in the -RBV group (RR = 5.18; 95% CI: 3.41 to 7.86; p < 0.00001).
CONCLUSION
The addition of RBV may not contribute to a higher SVR rate and could increase the incidence of anemia, so RBV is not necessary in SOF-based DAAs for patients with HCV recurrence after LT.
Topics: Antiviral Agents; Drug Therapy, Combination; Female; Hepatitis C; Humans; Liver Transplantation; Male; Middle Aged; Recurrence; Ribavirin; Sofosbuvir; Sustained Virologic Response
PubMed: 30959250
DOI: 10.1016/j.ijid.2019.03.038 -
Journal of Comparative Effectiveness... May 2019Hepatitis C virus (HCV) is a positive-stranded RNA virus which belongs to the family of , predominantly infecting liver hepatocytes. HCV infection is a major cause for...
Hepatitis C virus (HCV) is a positive-stranded RNA virus which belongs to the family of , predominantly infecting liver hepatocytes. HCV infection is a major cause for morbidity worldwide. The primary objective was to evaluate the comparative effectiveness of pan-genotypic therapies for the treatment of patients with HCV infection in Bulgaria. The databases MEDLINE, EMBASE, Cochrane Library, PubMed and clinicaltrials.gov were searched to identify studies evaluating the therapeutic efficacy of sofosbuvir/velpatasvir/voxilaprevir, sofosbuvir/velpatasvir and glecaprevir/pibrentasvir for the treatment of HCV patients. The range of sustained virologic response rates among all genotypes achieved after therapy with sofosbuvir/velpatasvir/voxilaprevir was 92-100% (8-week therapy) in treatment-naive patients and 99-100% (12-week therapy) in experienced patients. The range of sustained virologic response rates with glecaprevir/pibrentasvir was 91-100% (12-week therapy) and 97-100% (12-week therapy) with sofosbuvir/velpatasvir. Sofosbuvir/velpatasvir/voxilaprevir is a noninferior therapy offering a simple and short-term treatment regimen with high efficacy, favorable safety profile and good tolerability.
Topics: Aminoisobutyric Acids; Antiviral Agents; Bulgaria; Carbamates; Cyclopropanes; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; Humans; Lactams, Macrocyclic; Leucine; Macrocyclic Compounds; Proline; Quinoxalines; Sofosbuvir; Sulfonamides; Sustained Virologic Response
PubMed: 30920311
DOI: 10.2217/cer-2018-0143 -
Virology Journal Mar 2019Whether sofosbuvir is suitable for hepatitis C virus (HCV) infected patients with severe renal impairment is inconclusive. This systematic review aims to evaluate the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Whether sofosbuvir is suitable for hepatitis C virus (HCV) infected patients with severe renal impairment is inconclusive. This systematic review aims to evaluate the safety and effectiveness of SOF-based regimen in the setting of stage 4 and 5 chronic kidney disease (CKD).
METHODS
We conducted a systematic literature search in PubMed, Web of Science, EMBASE and Google Scholar with searching strategy: (sofosbuvir OR Sovaldi OR Harvoni OR Epclusa OR Vosevi) AND (severe kidney impairment OR severe renal impairment OR end-stage renal disease OR dialysis OR renal failure OR ESRD OR renal insufficiency OR hepatorenal syndrome OR HRS). Sustained virological response (SVR12/24) rate and serious adverse event (SAE) rate with 95% confidence intervals were aggregated. Subgroup analysis was implemented to evaluate the impact of treatment strategy and patient characteristics.
RESULTS
Twenty-one studies met inclusion criteria, totaling 717 HCV infected patients with CKD stage 4 or 5 (58.4% on dialysis). Pooled SVR12/24 was 97.1% (95% CI 93.9-99.3%), and SAE rate was 4.8% (95% CI 2.1-10.3%). There was no significant difference at SVR12/24 (97.1% vs 96.2%, p = 0.72) or SAE rate (8.8% vs 2.9%, p = 0.13) between subgroups applying full or decreased dose of sofosbuvir. Cirrhotic and non-cirrhotic patients achieved comparable sustained virological response (RR 0.93, 95% CI 0.85-1.02). Four studies reported eGFR/serum creatinine pre- and post- treatment, with no significant modification.
CONCLUSIONS
Our study suggests SOF-based regimen might be used safely and effectively in patients living with HCV infection/stage 4-5 CKD, with normal and reduced dose of sofosbuvir. Prospective and well-controlled trials are needed to confirm these findings.
TRIAL REGISTRATION
PROSPERO CRD42018107440 .
Topics: Antiviral Agents; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Kidney Failure, Chronic; Prospective Studies; Renal Insufficiency, Chronic; Ribavirin; Sofosbuvir; Sustained Virologic Response
PubMed: 30871566
DOI: 10.1186/s12985-019-1140-x -
Value in Health : the Journal of the... Feb 2019This paper constitutes the first attempt to draw lessons from the recent uptake of health economic evaluation of innovative drugs in the French regulatory framework.
OBJECTIVE
This paper constitutes the first attempt to draw lessons from the recent uptake of health economic evaluation of innovative drugs in the French regulatory framework.
STUDY DESIGN
Taking the example of new direct-acting antivirals against hepatitis C virus, the paper asks whether and how the cost-effectiveness (CE) opinions issued by the French National Health Authority improve the information available to support the pricing decisions.
METHODS
The analysis compares the assessment of these drugs based on three different sources: CE opinions, clinical opinions, and the published cost-utility analyses (CUA) available in the literature and identified through a systematic review.
RESULTS
The results show that CE opinions bring to the fore three issues prone to impact the incremental cost utility ratio and those were not available to the decision maker through clinical opinions or published CUA: the stage of treatment initiation, the modeling of the disease progression, and the uncertainty around the efficacy rates.
CONCLUSIONS
France has introduced the criterion of the cost per QALY gained in the pricing and regulation of innovative pharmaceuticals since 2013. Our analysis shows that the use of CUA does enhance the information available to the decision makers on the value of the treatments.
Topics: Antiviral Agents; Carbamates; Cost-Benefit Analysis; Economics, Medical; France; Hepatitis C; Humans; Imidazoles; Pyrrolidines; Sofosbuvir; Therapies, Investigational; Valine
PubMed: 30711067
DOI: 10.1016/j.jval.2018.08.009 -
Ophthalmic Research 2019A meta-analysis was performed to evaluate the safety and efficacy of topical 3% diquafosol in treating patients with dry eye disease (DED). (Meta-Analysis)
Meta-Analysis
PURPOSE
A meta-analysis was performed to evaluate the safety and efficacy of topical 3% diquafosol in treating patients with dry eye disease (DED).
METHODS
Nine qualified randomized controlled trials incorporating 1,467 patients were included. Two of the reviewers selected the studies and independently assessed the risk of bias. The outcome measures were Schirmer score, tear film break-up time (TFBUT), rose bengal staining score, and corneal fluorescein staining score. To confirm the effect of diquafosol on dryness after cataract surgery, we performed a subgroup analysis according to the presence or absence of surgery.
RESULTS
We observed statistically significant improvements in scores on the Schirmer test (weighted mean difference 0.74 mm at 4 weeks; 95% CI: 0.24-1.24; I2 = 0%), fluorescein stain, rose bengal stain, and TFBUT after treatment with diquafosol compared with the group using other eye drops. As a result of the subgroup analysis of DED after cataract surgery, diquafosol was found to be more effective than the other eye drops with regard to TFBUT and rose bengal staining.
CONCLUSIONS
Topical diquafosol could be an effective treatment for DED, and also for DED after cataract surgery. Further randomized controlled trials with larger sample sizes for the different clinical types of DED are warranted to determine the efficacy and limitations of diquafosol for these different clinical types of DED.
Topics: Cataract Extraction; Dry Eye Syndromes; Humans; Ophthalmic Solutions; Polyphosphates; Randomized Controlled Trials as Topic; Tears; Uracil Nucleotides
PubMed: 30654362
DOI: 10.1159/000492896 -
BMC Infectious Diseases Nov 2017Six distinct genetic variants (genotypes 1 - 6) of hepatitis C virus (HCV) exist globally. Certain genotypes are more prevalent in particular countries or regions... (Review)
Review
BACKGROUND
Six distinct genetic variants (genotypes 1 - 6) of hepatitis C virus (HCV) exist globally. Certain genotypes are more prevalent in particular countries or regions than in others but, globally, genotype 3 (GT3) is the second most common. Patients infected with HCV GT1, 2, 4, 5 or 6 recover to a greater extent, as measured by sustained virological response (SVR), following treatment with regimens based on direct-acting antivirals (DAAs) than after treatment with older regimens based on pegylated interferon (Peg-IFN). GT3, however, is regarded as being more difficult to treat as it is a relatively aggressive genotype, associated with greater liver damage and cancer risk; some subgroups of patients with GT3 infection are less responsive to current licensed DAA treatments. Newer DAAs have become available or are in development.
METHODS
According to PRISMA guidance, we conducted a systematic review (and descriptive statistical analysis) of data in the public domain from relevant clinical trial or observational (real-world) study publications within a 5-year period (February 2011 to May 2016) identified by PubMed, Medline In-Process, and Embase searches. This was supplemented with a search of five non-indexed literature sources, comprising annual conferences of the AASLD, APASL, CROI, EASL, and WHO, restricted to a 1-year period (April 2015 to May 2016).
RESULTS
Of the all-oral regimens, the efficacy (SVR12 ≥ 90%) of sofosbuvir plus daclatasvir- and velpatasvir-based regimens in clinical trials supports and reinforces their recommendation by guidelines. Other promising regimens comprise grazoprevir + elbasvir + sofosbuvir, and ombitasvir + paritaprevir/ribavirin + sofosbuvir. Newer regimens incorporating pibrentasvir + glecaprevir or grazoprevir + ruzasvir + MK-3682 (uprifosbuvir), offer all-oral, ribavirin-free SVR12 rates consistently greater than 95%. Observational studies report slightly lower overall SVR rates but reflect corresponding clinical trial data in terms of treatments most likely to achieve good responses.
CONCLUSIONS
On the basis of SVR12, we established that for treating GT3 infections (i) regimens incorporating newer DAAs are more effective than those comprising older DAAs, and (ii) ribavirin may be of less benefit in newer DAA regimens than in older DAA regimens. The analysis provides evidence that DAA regimens can replace Peg-IFN-based regimens for GT3 infection.
Topics: Antiviral Agents; Carbamates; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; Humans; Imidazoles; Pyrrolidines; Ribavirin; Sofosbuvir; Treatment Outcome; Valine
PubMed: 29145802
DOI: 10.1186/s12879-017-2820-z -
Journal of Infection and Public Health 2018Velpatasvir is a newly FDA-approved inhibitor of hepatitis C virus (HCV) NS5A protein. We performed this systematic review and meta-analysis to investigate the safety... (Meta-Analysis)
Meta-Analysis Review
Velpatasvir is a newly FDA-approved inhibitor of hepatitis C virus (HCV) NS5A protein. We performed this systematic review and meta-analysis to investigate the safety and efficacy of velpatasvir plus sofosbuvir in the treatment of chronic HCV infection. A computerized literature search of PubMed, SCOPUS, EMBASE, EBSCO, Web of science, and Cochrane CENTRAL was conducted using relevant keywords. Data from eligible studies were pooled in a fixed effect meta-analysis model, using OpenMeta[Analyst] software. Pooled data from six randomized trials (n=1427 patients) showed that velpatasvir plus sofosbuvir achieved sustained virological response (SVR12) rates of 98.2% in genotype-1, 99.4% in genotype-2, 94.7% in genotype-3, 99.6% in genotype-4, 97.1% in genotype-5, and 98.8% in genotype-6 patients. The addition of ribavirin did not significantly increase the SVR12 (RR=0.95, 95%CI [0.88, 1.02]) or decrease relapse rates (RR=2.52, 95% CI [0.49, 12.87]) in HCV genotype-1 patients. However, adding ribavirin significantly increased SVR12 (RR=89.5, 95% CI [80.4, 99.5]) in genotype-3 patients. In conclusion, the 12-week regimen of sofosbuvir plus velpatasvir was highly effective in HCV patients, including those with cirrhosis and former treatment experience. Except for genotype-3, adding ribavirin was not associated with significant improvements in SVR12 rates. Further studies should investigate the effect of adding ribavirin to this regimen, especially in HCV genotype-3 patients.
Topics: Antiviral Agents; Carbamates; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; Humans; Randomized Controlled Trials as Topic; Ribavirin; Sofosbuvir; Treatment Outcome; Viral Nonstructural Proteins
PubMed: 28970099
DOI: 10.1016/j.jiph.2017.09.004 -
Indian Journal of Pharmacology 2017Stroke and traumatic brain injury (TBI) are the critical public health and socioeconomic problems throughout the world. At present, citicoline is used as a coadjuvant... (Meta-Analysis)
Meta-Analysis Review
Stroke and traumatic brain injury (TBI) are the critical public health and socioeconomic problems throughout the world. At present, citicoline is used as a coadjuvant for the management of acute ischemic stroke (AIS) and TBI in various countries. This systemic review analyzes the beneficial role of citicoline in AIS and TBI. This systemic review is based on "PubMed" and "Science Direct" search results for citicoline role in stroke and TBI. In this systemic review, we included 12 human trials. A meta-analysis was performed on the basis of neurological evaluation, functional evaluation and Glasgow outcome scale, domestic adaptation evaluation outcomes, and cognitive outcome individually. In neurological evaluation, domestic adaptation evaluation, and cognitive outcomes, there was no significant difference in both the citicoline and placebo groups (odds ratio [OR] = 1.04 [0.9-1.2, = 0.583]; OR = 1.1 [0.94-1.27, = 0.209]; OR = 0.953 [0.75-1.2, = 0.691]). In evaluation of functional outcomes, there was significant difference in both groups and OR was 1.18 (1.04-1.34, = 0.01). Functional outcomes were significantly improved by citicoline, but the positive role of this drug in neurological recovery, domestic adaptation, and cognitive outcomes is still a topic of discussion for future.
Topics: Humans; Brain Injuries, Traumatic; Brain Ischemia; Cognition; Cytidine Diphosphate Choline; Nootropic Agents; Stroke; Treatment Outcome
PubMed: 28458415
DOI: 10.4103/0253-7613.201037 -
Daru : Journal of Faculty of Pharmacy,... Apr 2017Hepatitis C virus (HCV) infection is an important cause of chronic liver disease which has been affected 3% of world's population. Some studies have shown that adding... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatitis C virus (HCV) infection is an important cause of chronic liver disease which has been affected 3% of world's population. Some studies have shown that adding Sofosbuvir (SOF), an HCV polymerase inhibitor to the conventional therapy of Pegylated-interferon (PegIFN) plus Ribavirin (RBV) can increase the rate of sustained virologic response (SVR) among HCV-infected patients. This study was conducted to determine the effect of combination therapy with PegIFN and RBV plus SOF for chronic hepatitis C genotype 1 infection using systematic review with meta-analysis.
METHODS
In this study, electronic databases including PubMed, Scopus, Science Direct, and Web of Science were comprehensively searched using appropriate strategies containing all related keywords of "hepatitis C", "PegIFN", "RBV" and "SOF". Studies assessed the efficacy of combination therapy with PegIFN and RBV plus SOF for chronic hepatitis C genotype 1 infection were included in the meta-analysis.
RESULTS
After screening of 757 records, we included five articles with total sample size of 411 to the meta-analysis. Based on the fixed-effect model (χ = 5.29, P = 0.26 and I = 24.4%), pooled SVR rate for treatment regimen of PegIFN and RBV plus SOF was calculated as 88.54% (95% CI = 85.77%-91.32%).
CONCLUSIONS
Combination therapy with PegIFN and RBV plus SOF results in high treatment response in patients with HCV genotype 1 infection.
Topics: Antiviral Agents; Drug Therapy, Combination; Hepacivirus; Hepatitis C, Chronic; Humans; Interferon-alpha; Ribavirin; Sofosbuvir
PubMed: 28427463
DOI: 10.1186/s40199-017-0177-x