Evaluation of the Safety Profile of Direct-Acting Antivirals on Patients with Hepatitis C Virus: A Pharmacovigilance Study

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Abstract

Background

Hepatitis C virus (HCV) is the primary contributor to chronic hepatic diseases. A rapid change in the situation took place with the advent of oral direct-acting antivirals (DAAs). However, a comprehensive review of the adverse event (AE) profile of the DAAs is lacking. This cross-sectional study aimed to analyze the reported Adverse Drug Reactions (ADRs) with DAA treatment using data from VigiBase, the WHO Individual Case Safety Report (ICSR) database.

Methods

All ICSRs reported to VigiBase with sofosbuvir (SOF), daclatasvir (DCV), sofosbuvir /ledipasvir (SOF/LDV) and ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) in Egypt were extracted. Descriptive analysis was performed to summarize patients’ and reactions’ characteristics. Information components (ICs) and proportional reporting ratios (PRRs) for all reported ADRs were calculated to identify signals of disproportionate reporting. Logistic regression analysis was performed to identify the DAAs association with serious events of concern while adjusting for age, gender, pre-existing cirrhosis, and ribavirin use.

Results

Out of 2925 reports, 1131 (38.6%) were serious. The most commonly reported reactions; anaemia (21.3%), HCV relapse (14.5%) and headache (14%). For the disproportionality signals; HCV relapse was reported with SOF/DCV (IC 3.65, 95% CrI 3.47–3.79) and SOF/RBV (IC 3.69, 95% CrI 3.37–3.92), while anaemia (IC 2.85, 95% CrI 2.26–3.27) and renal impairment (IC 2.12, 95% CrI 0.7–3.03) were reported with OBV/PTV/r.

Conclusion

The highest severity index and seriousness were reported with SOF/RBV regimen. A significant association was found for OBV/PTV/r with renal impairment and anaemia although being the superior regimen in terms of efficacy. The study findings call for further population-based studies for clinical validation.

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Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Theo Vos, Stephen S Lim, Cristiana Abbafati … (2023)

Summary Background In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and development investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding Bill & Melinda Gates Foundation.

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Sofosbuvir and ribavirin in HCV genotypes 2 and 3.

Stefan Zeuzem, Geoffrey M Dusheiko, Riina Salupere … (2014)

In clinical trials, treatment with a combination of the nucleotide polymerase inhibitor sofosbuvir and the antiviral drug ribavirin was associated with high response rates among patients with hepatitis C virus (HCV) genotype 2 infection, with lower response rates among patients with HCV genotype 3 infection. We conducted a study involving patients with HCV genotype 2 or 3 infection, some of whom had undergone previous treatment with an interferon-based regimen. We randomly assigned 91 patients with HCV genotype 2 infection and 328 with HCV genotype 3 infection, in a 4:1 ratio, to receive sofosbuvir-ribavirin or placebo for 12 weeks. On the basis of emerging data from phase 3 trials indicating that patients with HCV genotype 3 infection had higher response rates when they were treated for 16 weeks, as compared with 12 weeks, the study was unblinded, treatment for all patients with genotype 3 infection was extended to 24 weeks, the placebo group was terminated, and the goals of the study were redefined to be descriptive and not include hypothesis testing. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. Of the 419 patients who were enrolled and treated, 21% had cirrhosis and 58% had received previous interferon-based treatment. The criterion for a sustained virologic response was met in 68 of 73 patients (93%; 95% confidence interval [CI], 85 to 98) with HCV genotype 2 infection who were treated for 12 weeks and in 213 of 250 patients (85%; 95% CI, 80 to 89) with HCV genotype 3 infection who were treated for 24 weeks. Among patients with HCV genotype 3 infection, response rates were 91% and 68% among those without and those with cirrhosis, respectively. The most common adverse events were headache, fatigue, and pruritus. Therapy with sofosbuvir-ribavirin for 12 weeks in patients with HCV genotype 2 infection and for 24 weeks in patients with HCV genotype 3 infection resulted in high rates of sustained virologic response. (Funded by Gilead Sciences; VALENCE ClinicalTrials.gov number, NCT01682720.).

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Screening and Treatment Program to Eliminate Hepatitis C in Egypt

Imam Waked, Gamal Esmat, Aisha Elsharkawy … (2020)

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Author and article information

Contributors

Mai G. El-Marakby:

ORCID: http://orcid.org/0000-0001-8241-5223

mai.gamal21@pharma.asu.edu.eg

Mohamed H. Solayman: mohamed_solayman@pharma.asu.edu.eg

Nagwa A. Sabri:

ORCID: http://orcid.org/0000-0002-2611-4853

nagwa.sabri@pharma.asu.edu.eg

Journal

Journal ID (nlm-ta): Ther Innov Regul Sci

Journal ID (iso-abbrev): Ther Innov Regul Sci

Title: Therapeutic Innovation & Regulatory Science

Publisher: Springer International Publishing (Cham )

ISSN (Print): 2168-4790

ISSN (Electronic): 2168-4804

Publication date (Electronic): 25 May 2023

Publication date PMC-release: 25 May 2023

Publication date (Print): 2023

Volume: 57

Issue: 5

Pages: 997-1007

Affiliations

GRID grid.7269.a, ISNI 0000 0004 0621 1570, Clinical Pharmacy Department, Faculty of Pharmacy, , Ain Shams University, ; Cairo, Egypt

Author information

Mai G. El-Marakby http://orcid.org/0000-0001-8241-5223

Nagwa A. Sabri http://orcid.org/0000-0002-2611-4853

Article

Publisher ID: 537

DOI: 10.1007/s43441-023-00537-x

PMC ID: 10400676

PubMed ID: 37227588

SO-VID: e3152ea3-b6ae-4d93-a2a5-dc698365ba31

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 19 December 2022

Date accepted : 5 May 2023

Funding

Funded by: Ain Shams University

Open Access :

Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB).

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Keywords: direct-acting antiviral,hepatitis c virus,pharmacovigilance,adverse reaction,vigibase

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Keywords: direct-acting antiviral, hepatitis c virus, pharmacovigilance, adverse reaction, vigibase

Evaluation of the Safety Profile of Direct-Acting Antivirals on Patients with Hepatitis C Virus: A Pharmacovigilance Study

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Most cited references 35

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Sofosbuvir and ribavirin in HCV genotypes 2 and 3.

Screening and Treatment Program to Eliminate Hepatitis C in Egypt

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