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Frontiers in Public Health 2022This study aims to systematically review recent economic evaluations of elbasvir/grazoprevir (EBR/GZR) for chronic hepatitis C (CHC), to critically appraise the...
OBJECTIVE
This study aims to systematically review recent economic evaluations of elbasvir/grazoprevir (EBR/GZR) for chronic hepatitis C (CHC), to critically appraise the reporting quality and to summarize the results.
METHODS
A literature search was undertaken using Medline, Embase, the Cochrane Library, EconLit, China National Knowledge Infrastructure, Wanfang Data, and Chongqing VIP to identify original articles containing economic evaluations of EBR/GZR for CHC published between 1 January 2000 and 31 December 2020. The Consolidated Health Economic Evaluation Reporting Standards statement was used to assess the quality of reporting of the articles.
RESULTS
Of 93 articles identified, 13 studies fulfilled the inclusion criteria. These studies were conducted in 4 countries, and 8 active interventions were assessed. The target population was patients infected with CHC genotype 1 infection in all studies. Eight out of 13 studies that compared EBR/GZR vs. other direct antiviral agents suggested that EBR/GZR was generally more cost-effective or dominant than daclatasvir/asunaprevir (DCV/ASV), sofosbuvir/velpatasvir (SOF/VEL), ledipasvir/sofosbuvir (LDV/SOF), ombitasvir/paritaprevir/ritonavir + dasabuvir (3D) but not more cost-effective than glecaprevir/pibrentasvir (GLE/PIB). Two studies from China and one study from the USA that compared EBR/GZR vs. pegylated interferon and ribavirin (PegIFN/RBV) consistently indicated that EBR/GZR was generally more cost-effective than PegIFN/RBV. One study from Italy compared EBR/GZR with SOF + PegIFN/RBV and suggested that EBR/GZR had a lower cost and higher effectiveness. One study from France and one study from the USA confirmed that compared with non-therapy for patients with chronic kidney disease, EBR/GZR was cost-effective at commonly accepted current standards. All included studies were of good quality of reporting, with an average score of 21.9 (range 19-23).
CONCLUSION
EBR/GZR for CHC genotype 1 might be cost-effective or dominant compared with PegIFN/RBV and other direct antiviral agents (SOF/VEL, 3D, DCV/ASV, LDF/SOF) or non-therapy. However, under certain assumptions, EBR/GZR was not a cost-effective alternative for CHC patients vs. GLE/PIB.
Topics: Amides; Antiviral Agents; Benzofurans; Carbamates; Cost-Benefit Analysis; Cyclopropanes; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Quinoxalines; Ribavirin; Sofosbuvir; Sulfonamides
PubMed: 35646774
DOI: 10.3389/fpubh.2022.836986 -
Annals of Hepatology 2021Patients with hepatitis C virus (HCV) genotype 3 (GT3) infection are resistant to direct-acting antiviral (DAA) treatments. This study aimed to analyze the effectiveness... (Meta-Analysis)
Meta-Analysis
Patients with hepatitis C virus (HCV) genotype 3 (GT3) infection are resistant to direct-acting antiviral (DAA) treatments. This study aimed to analyze the effectiveness of sofosbuvir (SOF)+daclatasvir (DCV) ± ribavirin (RBV); SOF+velpatasvir (VEL)±RBV; SOF+VEL+voxilaprevir (VOX); and glecaprevir (GLE)+pibrentasvir (PIB) in the treatment of HCV GT3-infected patients in real-world studies. Articles were identified by searching the PubMed, EMBASE, and Cochrane Library databases from January 1, 2016 to September 10, 2019. The meta-analysis was conducted to determine the sustained virologic response (SVR) rate, using R 3.6.2 software. Thirty-four studies, conducted on a total of 7328 patients from 22 countries, met the inclusion criteria. The pooled SVR rate after 12/24 weeks of treatment was 92.07% (95% CI: 90.39-93.61%) for the evaluated regimens. Also, the SVR rate was 91.17% (95% CI: 89.23-92.94%) in patients treated with SOF+DCV±RBV; 95.08% (95% CI: 90.88-98.13%) in patients treated with SOF+VEL±RBV; 84.97% (95% CI: 73.32-93.91%) in patients treated with SOF+VEL+VOX; and 98.54% (95% CI: 96.40-99.82%) in patients treated with GLE+PIB. The pooled SVR rate of the four regimens was 95.24% (95% CI: 93.50-96.75%) in non-cirrhotic patients and 89.39% (95% CI: 86.07-92.33%) in cirrhotic patients. The pooled SVR rate was 94.41% (95% CI: 92.02-96.42%) in treatment-naive patients and 87.98% (95% CI: 84.31-91.25%) in treatment-experienced patients. The SVR rate of GLE+PIB was higher than other regimens. SOF+VEL+VOX can be used as a treatment regimen following DAA treatment failure.
Topics: Antiviral Agents; Benzimidazoles; Carbamates; Drug Combinations; Hepatitis C; Heterocyclic Compounds, 4 or More Rings; Humans; Imidazoles; Macrocyclic Compounds; Pyrrolidines; Quinoxalines; Ribavirin; Sofosbuvir; Sulfonamides; Valine
PubMed: 33059055
DOI: 10.1016/j.aohep.2020.09.012 -
Nefrologia 2021Hepatitis C is an important agent of liver damage in patients with chronic kidney disease and the advent of DAAs has dramatically changed the management of HCV positive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepatitis C is an important agent of liver damage in patients with chronic kidney disease and the advent of DAAs has dramatically changed the management of HCV positive patients, including those with advanced CKD. Sofosbuvir is the backbone of many anti-HCV regimens based on DAAs but it remains unclear whether it is appropriate for HCV-infected patients with stage 4-5 CKD.
STUDY AIMS AND DESIGN
We performed a systematic review of the literature with a meta-analysis of clinical studies in order to evaluate the efficacy and safety of SOF-based DAA regimens in patients with stage 4-5 CKD. The primary outcome was sustained viral response (as a measure of efficacy); the secondary outcomes were the frequency of SAEs and drop-outs due to AEs (as measures of tolerability). The random-effects model of DerSimonian and Laird was adopted, with heterogeneity and stratified analyses.
RESULTS
Thirty clinical studies (n=1537 unique patients) were retrieved. The pooled SVR12 and SAEs rate was 0.99 (95% confidence intervals, 0.97; 1.0, I=99.8%) and 0.09 (95% CI, 0.05; 0.13, I=84.3%), respectively. The pooled SVR12 rate in studies with high HCV RNA levels at baseline was lower, 0.87 (95% CI, 0.75; 1.0, I=73.3%) (P<0.001). The pooled drop-out rate due to AEs was 0.02 (95% CI, -0.01; 0.04, I=16.1%). Common serious adverse events were anemia (n=26, 38%) and reduced eGFR (n=14, 19%). SAEs were more common in studies adopting full-dose sofosbuvir (pooled rate of SAEs 0.15, 95% CI, 0.06; 0.25; I=80.1%) and in those based on ribavirin (0.15, 95% CI, 0.07; 0.23, I=95.8%). Six studies (n=69 patients) reported eGFR levels at baseline/post- antiviral therapy; no consistent changes were found.
CONCLUSIONS
SOF-based regimens appear safe and effective in patients with stage 4-5 CKD. Serum creatinine should be carefully monitored during therapy with SOF in patients with CKD. Randomized controlled studies in order to expand our knowledge on this point are under way.
Topics: Antiviral Agents; Creatinine; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Kidney Failure, Chronic; RNA; Renal Insufficiency, Chronic; Ribavirin; Sofosbuvir; Sustained Virologic Response
PubMed: 36165141
DOI: 10.1016/j.nefroe.2021.11.011 -
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 -
Alimentary Pharmacology & Therapeutics Jan 2020Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection is highly curative and tolerable. Among patients with hepatocellular carcinoma (HCC), optimal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection is highly curative and tolerable. Among patients with hepatocellular carcinoma (HCC), optimal timing of DAA therapy remains unclear. Data on efficacy of DAA therapy in patients with HCC would inform this decision-making.
AIM
To evaluate response to DAA therapy among patients diagnosed with HCV infection and HCC.
METHODS
Bibliographic databases and conference abstracts were searched. Meta-analysis was conducted to pool sustained virologic response (SVR) estimates.
RESULTS
Fifty-six studies with 5522 patients with HCV and HCC were included. Overall SVR was 88.3% (95% CI 86.1-90.4). Twenty-seven studies included patients with prior or present HCC (n = 3126) and patients without HCC (n = 49 138), in which SVR was 88.2% (95% CI 85.0-91.4) and 92.4% (95% CI 91.1-93.7) among patients with and without HCC, respectively (odds ratio: 0.54, 95% CI 0.43-0.68, P < .001). In the subgroup analyses, higher SVR was seen in patients who received curative HCC management (SVR 90.4%, 95% CI 88.3-92.4), or treated with sofosbuvir + NS5A inhibitor DAAs (SVR 96.9%, 95% CI 94.3-99.4), or in patients with HCV genotype 1 infection (SVR 92.0%, 95% CI 88.1-95.6).
CONCLUSION
Response to DAA therapy was lower in patients with HCC compared to those without HCC, regardless of cirrhosis status. Among HCC patients, there was an impact of proportion with curative HCC management on DAA therapy response.
Topics: Antiviral Agents; Carcinoma, Hepatocellular; Hepatitis C; Humans; Liver Cirrhosis; Liver Neoplasms; Sofosbuvir; Sustained Virologic Response; Treatment Outcome
PubMed: 31808566
DOI: 10.1111/apt.15598 -
Journal of Gastroenterology and... Apr 2017Ledipasvir with sofosbuvir (LED/SOF) for the treatment of patients infected with genotype 1 hepatitis C virus can be used with or without ribavirin (RBV). RBV is well... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
Ledipasvir with sofosbuvir (LED/SOF) for the treatment of patients infected with genotype 1 hepatitis C virus can be used with or without ribavirin (RBV). RBV is well known to promote significant adverse events (AE). The aim of this study was to compare the efficacy and safety of treatment with LED/SOF, with or without RBV, in patients infected with hepatitis C virus genotype 1.
METHODS
We performed a systematic review followed by a pairwise meta-analysis including randomized controlled trials that reported efficacy (rapid virological response, sustained virological response at 4 and 12 weeks post-treatment (SVR4 and 12), and viral relapse) and safety outcomes (any AE, serious AE, discontinuation owing to AE, anemia, and rash). It was performed a subgroup analysis evaluating the SVR12 including only cirrhotic patients. Results were reported as risk ratios (RR) and with 95% confidence intervals (95% CI).
RESULTS
Seven randomized controlled trials were analyzed. LED/SOF with RBV showed a worse safety profile when compared with LED/SOF without RBV for the following outcomes: any AE (RR 0.56 [95% CI 0.46-0.69]), anemia (RR 0.08 [95% CI 0.04-0.17]), and rash (RR 0.35 [95% CI 0.19-0.65]). No significant differences were observed regarding serious AE, rapid virological response, SVR4, SVR12, or viral relapse. The subgroup analysis did not show significant differences between either treatment groups.
CONCLUSION
Administration of LED/SOF + RBV to treatment-naïve patients with or without cirrhosis, and non-cirrhotic treatment-experienced patients, did not promote significant additional benefits. Furthermore, it is still unclear whether cirrhotic treatment-experienced patients could benefit from combined therapy.
Topics: Antiviral Agents; Benzimidazoles; Databases, Bibliographic; Drug Therapy, Combination; Fluorenes; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Randomized Controlled Trials as Topic; Ribavirin; Sofosbuvir; Treatment Outcome
PubMed: 27785825
DOI: 10.1111/jgh.13620 -
Journal of Alzheimer's Disease : JAD 2020A critical strategy in the management of Alzheimer's disease (AD) is optimizing the effects of currently available pharmacologic therapies such as citicoline (CC).
BACKGROUND
A critical strategy in the management of Alzheimer's disease (AD) is optimizing the effects of currently available pharmacologic therapies such as citicoline (CC).
OBJECTIVE
The purpose of this study was to determine the effects of CC as adjunct therapy to cholinesterase inhibitors (AChEI) in the treatment of AD.
METHODS
We identified relevant studies by electronic search until April 2020. We considered studies with a comparator group that enrolled elderly patients with a diagnosis of AD and employed CC as an adjunct therapy to AChEIs compared to AChEI monotherapy or comparisons of different AChEIs combined with CC. Methodological quality assessment was done using the Newcastle-Ottawa Scale.
RESULTS
Out of 149 articles identified, two retrospective cohort studies involving 563 elderly patients affected with AD were included. After 3 months and 9 months, better Mini-Mental Status Examination scores were observed in the "AChEIs + CC" group versus "AChEIs alone" group. CC combined with donepezil may be better in improving cognition than when combined with rivastigmine. No significant difference was noted in terms of activities of daily living (ADL) and instrumental-ADL. Neuropsychiatric Inventory and Geriatric Depression Scale-short form scores appeared to be lower in the combination treatment versus monotherapy. The adverse events of combined treatment were self-limiting and included occasional excitability, gastric intolerance, and headache.
CONCLUSION
Limited evidence from pooled data of two observational studies suggests that CC used in adjunct with AChEIs in the treatment of AD was well-tolerated and showed improvement in cognition, mood, and behavioral symptoms compared to treating with AChEIs alone.
Topics: Alzheimer Disease; Case-Control Studies; Cognition; Cytidine Diphosphate Choline; Drug Therapy, Combination; Humans; Nootropic Agents; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32538854
DOI: 10.3233/JAD-200378 -
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 -
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 -
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