Real life experience with direct-acting antivirals agents against hepatitis C infection in elderly patients

doi:10.1016/j.jcv.2017.01.003

Journal of Clinical Virology

Volume 88, March 2017, Pages 58-61

https://doi.org/10.1016/j.jcv.2017.01.003 Get rights and content

Highlights

•
Efficacy and safety of different DAAs have opened the possibility to treat many special populations as elderly patients.
•
Most of elderly patients are on chronic medications (86.7%). An adjustment was needed for 35.8% of patients.
•
This study identifies ribavirin and protein inhibitor based regimen as the most likely drugs to cause adverse events.
•
Two patients were diagnosed with hepatocellular carcinoma during treatment.
•
ITT analyses showed a sustained virological response of 88.3%. No associated factor was linked to treatment failure.

Abstract

Background

New direct-acting antivirals agents (DAAs) are very safe and well tolerated.

Objectives

The purpose of this study is to analyse the efficacy and safety of DAAs in elderly patients, who have co-morbidities and are on chronic medications.

Study design

All HCV-infected patients over 65 years old in clinical follow-up at two Hospitals in Spain who initiated anti-HCV therapy were included (August 2012–October 2015).

Results

A total of 120 HCV mono-infected patients were recorded. Mean age of patients was 72.6 ± 7.4 years. There were 53.3% women and GT1b was the most frequent (83.3%); 64.2% had cirrhosis and 42.5% were treatment experienced. Ombitasvir + Paritaprevir/r ± Dasabuvir ± Ribavirin (RBV) and sofosbuvir/ledipasvir ± RBV were the most frequently used regimens. Weight-adjusted dosing of RBV was included in 61.7% and 43.6% of them required a dose reduction. Most of the patients (86.7%) had concomitant chronic medication and in 35.8% adjustment was necessary. Adverse events (AE) were seen in 65% of the patients; more frequent when a protease inhibitor (PI) was being used. The sustained virological response (SVR12) per ITT was 88.3%. Only 3 patients discontinued treatment and 2 patients died.

Conclusions

High rates of SVR12 (88.3%) were observed among elderly patients with DAAs-based regimens. The presence of AE was frequent (65%). The majority of these patients (86.7%) had concomitant medication that required adjustment in 1/3 of them. These findings highlight the high rates of response to DAAs in the elderly HCV-population. However, special caution must be taken when using RBV and a PI.

Graphical abstract

High rates of SVR12 (88.3%) were observed among elderly patients with DAAs-based regimens. The majority of these patients (86.7%) had concomitant medication that required adjustment in 1/3 of them. The presence of adverse event was frequent (65%) during HCV treatment, more frequent when a protein inhibitor or ribavirin was part of the regimen. Adverse events and modification of chronic medications make these patients a special population, where we had to exercise more care.

Section snippets

Backgorund

Hepatitis C Virus infection (HCV) continues to be a major public health problem affecting 130–150 million people globally [1]. The prevalence of chronic hepatitis C virus (CHC) infection in Spain is estimated around 2.5%–2.9%, and it increases with age [2], [3], [4], [5]. Most studies have consistently found that age and age onset of infection are major factors influencing the degree of fibrosis. In patients over 50-years-old, the rate of progression of fibrosis accelerates, regardless of the

Objectives

In this context, the purpose of this study is to analyse the efficacy and safety of different anti HCV treatments including DAAs in a real-life cohort of elderly patients.

Study design

This is an observational prospective study including all CHC infected patients over 65 years old who received HCV treatment based on DAAs at two hospitals in the Northwest Spain between August 2012 and October 2015.

The study protocol was reviewed and approved by a Medical Ethics Committee and this publication is in accordance with the community standards. All the study participants were informed before the study inclusion.

All demographic, virological, clinical, laboratory, liver fibrosis

Results

A total of 120 CHC monoinfected patients were included. Main demographic and virological characteristics are described in Table 1. Mean age of patients was 72.6 ± 7.4 years, there were 53.3% women, 100% were caucasian and GT1b was the most frequent (83.3%). 64.2% had cirrhosis.

The specific treatment combinations and the AE related to the study medication are depicted in Table 2. Briefly, 3D/2D ± RBV and SOF/LDV ± RBV were the most frequently used regimens. The duration of HCV treatment was in the

Discussion

This study evaluates the safety and efficacy of different DAAs based therapies among mono-infected CHC elderly patients in clinical follow-up in Spain. The SVR12 per ITT was 88.3%. Although the number of elderly patients in our cohort treated with the different new regimens, it does not allow us to conclude which are the most tolerated regimens.

This study identifies RBV and PI as the most likely drugs to cause AE. In this cohort, when a PI is part of the regimen, AE were three times more

Conflicts of interest

All authors declare no conflicts of interest.

Funding

This work was supported in part by grants from Fondo de Investigación Sanitaria (CPII14/00014, PI10/02166, PI13/02266, CM15/00233) and Fundación Profesor Novoa Santos, A Coruña.

Ethical approval

Acknowledgments

We would like to thank Biobank of A Coruña (SERGAS) for providing us the technical, ethical and legal advice necessary for the development of our research. We also thank the collaboration of Josefina Baliñas (HIV and Viral Hepatitis Unit, Complejo Hospitalario Universitario A Coruña).

References (19)

J.I. Esteban et al.
The changing epidemiology of hepatitis C virus infection in Europe
J. Hepatol.
(2008)
A.L. Mindikoglu et al.
Hepatitis C in the elderly: epidemiology, natural history and treatment
Clin. Gastroenterol. Hepatol.
(2009)
M. Buti et al.
Estimating the impact of hepatitis C virus therapy on future liver-related morbidity, mortality and costs related to chronic hepatitis C
J. Hepatol.
(2005 May)
World Health Organitation
Hepatitis C
(2016)
B. Hajarizadeh et al.
Epidemiology and natural history of HCV infection
Nat. Rev. Gastroenterol. Hepatol.
(2013)
S. Riestra et al.
Prevalence of hepatitis C virus infection in the general population of northern Spain
Eur. J. Gastroenterol. Hepatol.
(2001)
A. Mena et al.
Seroprevalence of HCV and HIV infections by year of birth in Spain: impact of US CDC and USPSTF recommendations for HCV and HIV testing
PLoS One
(2014)
A. Suárez et al.
The prevalence of hepatitis A, B and C viral markers in the population of Gijón between 26 and 65 years old
Gastroenterol. Hepatol.
(1997)
World Health Organisation, Sixty-seventh World Health Assembly. Viral hepatitis: WHA 67.6. Geneva, Switzerland, 24 May...

There are more references available in the full text version of this article.

Cited by (25)

Identification and management of contraindicated drug–drug interactions through pharmaceutical care programs: Experience in direct-acting antivirals therapy
2022, Journal of the Formosan Medical Association
To investigate the impact of pharmaceutical care programs for the management of contraindicated drug–drug interactions (DDIs) in direct-acting antivirals (DAAs) therapy.
A prospective observational study was performed at Dalin Tzu Chi Hospital between January 2018 and December 2019. Pharmacists screened DDIs for all hepatitis C patients before DAA therapy. The study outcome included the frequency of contraindicated DDIs, acceptance rate, and cost avoidance of the pharmaceutical care program.
A total of 1053 patients were enrolled in the study, with a mean age of 67.1 ± 11.9 years. Most patients received therapy with sofosbuvir/ledipasvir (37.1%; n = 391), elbasvir/grazoprevir (23.8%; n = 251), or glecaprevir/pibrentasvir (21.1%; n = 222). A total of 796 (75.6%) patients received at least one co-medication, with the average number of co-medications being 5.2 per patient (SD: 4.4/patient). In total, 1356 DDIs were identified, with the average DDIs per patient of 1.3 (SD: 1.7). For patients with contraindicated DDIs (2%, n = 102), statins and amiodarone were the most common co-medications. Physicians often accepted pharmacists’ recommendations (acceptance rate of 72.5%) or withheld co-medication to avoid severe adverse drug events (ADEs). The estimated cost avoidance of preventable ADEs was USD 14,033 for contraindicated DDIs with pharmaceutical care programs.
The implementation of pharmaceutical care programs in DAA therapy provides a favorable outcome and substantial cost avoidance.
Importance of adherence to treatment with direct-acting antivirals in hepatitis C
2019, Gastroenterologia y Hepatologia
Con la aparición de los antivirales de acción directa (AAD) y la implantación del Plan Estratégico Nacional, el espectro de pacientes con criterios de tratamiento se ha ampliado hasta abarcar la totalidad de estos. Ha habido una evolución en el perfil del paciente, que en su mayoría actualmente son pacientes no tratados previamente, con una menor conciencia de la enfermedad, polimedicados, y en muchos casos se trata de pacientes en terapia sustitutiva de opiáceos, usuarios activos de drogas o con comorbilidad psiquiátrica. Se hace una revisión de los factores más importantes que determinan el grado de adherencia, entre los que cabe destacar la complejidad farmacoterapéutica, los efectos adversos de los AAD, los factores demográficos (edad, etnia, sexo, nivel educacional, estado civil) y los psicosociales (creencias, motivación sobre la terapia y actitud negativa sobre esta), así como la relación médico-paciente, el conocimiento/conciencia de la enfermedad y, finalmente, las comorbilidades y el abuso de drogas u otras sustancias como el alcohol.
Información sobre el suplemento: este artículo forma parte del suplemento titulado “El valor de la simplicidad en el tratamiento de la hepatitis C”, que ha sido patrocinado por Gilead.
© 2019 Elsevier España, S.L.U. Todos los derechos reservados.
The introduction of direct-acting antivirals (DAA) and the implementation of the National Strategic Plan has extended the spectrum of patients suitable for treatment to include practically all affected individuals. There has been a change in patient profile. Most patients are previously untreated, with lesser awareness of the disease, and taking polymedication, and are often under treatment with opioid replacement therapy, are active drug users or have psychiatric comorbidities. This article reviews the most important factors determining the degree of treatment adherence, in particular, drug therapy complexity, the adverse effects of DAA, demographic factors (age, ethnic group, sex, educational level, marital status) and psychosocial factors (beliefs, motivation to take therapy and negative attitude to therapy), as well as the doctor-patient relationship, knowledge/awareness of the disease, and finally comorbidities and drug abuse or abuse of other substances such as alcohol.
Supplement information: This article is part of a supplement entitled “The value of simplicity in hepatitis C treatment”, which is sponsored by Gilead.
© 2019 Elsevier España, S.L.U. All rights reserved.
Efficacy and Pharmacokinetics of Glecaprevir and Pibrentasvir With Concurrent Use of Acid-Reducing Agents in Patients With Chronic HCV Infection
2019, Clinical Gastroenterology and Hepatology
Proton pump inhibitors (PPIs) are commonly prescribed to treat acid-related disorders. Some direct-acting antiviral regimens for chronic hepatitis C virus (HCV) infection have reduced efficacy in patients taking concomitant acid-reducing agents, including PPIs, due to interactions between drugs. We analyzed data from 9 multicenter, phase 2 and 3 trials to determine the efficacy and pharmacokinetics of an HCV therapeutic regimen comprising glecaprevir and pibrentasvir (glecaprevir/pibrentasvir) in patients taking concomitant acid-reducing agents.
We analyzed data from 2369 patients infected with HCV genotypes 1–6 and compensated liver disease treated with an all-oral regimen of glecaprevir/pibrentasvir for 8–16 weeks. We compared efficacy and pharmacokinetics among patients receiving at least 1 dose of an acid-reducing agent (a PPI, an H2 blocker, or antacid). High-dose PPI was defined as daily dose greater than 20 mg omeprazole dose equivalent. The objectives were to evaluate rate of sustained virologic response 12 weeks post-treatment (SVR12) and to assess steady-state glecaprevir and pibrentasvir exposures in patients on acid-reducing agents.
Of the 401 patients (17%) who reported use of acid-reducing agents, 263 took PPIs (11%; 109 patients took a high-dose PPI and 154 patients took a low-dose PPI). Rates of SVR12 were 97.0% among patients who used acid-reducing agents and 97.5% among those not using acid-reducing agents (P = .6). An SVR12 was achieved in 96.3% taking a high-dose PPI and 97.4% taking a low-dose PPI, with no virologic failures in those receiving a high-dose PPI (P = .7). Glecaprevir, but not pibrentasvir, bioavailability was affected; its exposure decreased by 41% in patients taking a high-dose PPI.
In an analysis of data from 9 clinical trials, we observed a high rate of SVR12 (approximately 97%) among patients treated with glecaprevir/pibrentasvir for HCV infection—even among patients taking concomitant ARA or high-dose PPI. This was despite decreased glecaprevir exposures in patients when on high-dose PPIs. ClinicalTrials.gov numbers, NCT02243280 (SURVEYOR-I), NCT02243293 (SURVEYOR-II), NCT02604017 (ENDURANCE-1), NCT02640482 (ENDURANCE-2), NCT02640157 (ENDURANCE-3), NCT02636595 (ENDURANCE-4), NCT02642432 (EXPEDITION-1), NCT02651194 (EXPEDITION-4), NCT02446717 (MAGELLAN-I).
Effects of age on treatment of chronic hepatitis C with direct acting antivirals
2019, Annals of Hepatology
Citation Excerpt :
As expected, the proportion of patients with comorbidities and taking concomitant medications increased with age. The number of medications taken probably also increased as in other studies8,11,18 making the risk of clinically significant drug-drug interactions more frequent in older patients.8,18 In observational studies, the treated patients are obviously selected, even if there is no imposed limit on age.
Data on the efficacy and tolerance of interferon-free treatment in chronic hepatitis C (CHC) in elderly patients are limited in phase II-III trials.
A prospective cohort of adult patients with CHC treated in French general hospitals.
Data from 1,123 patients, distributed into four age groups, were analyzed. Of these, 278 were > 64 years old (fourth quartile) and 133 were > 73 years old (tenth decile). Elderly patients weighed less, were more frequently treatment-experienced women infected with genotype 1b or 2, while they less frequently had genotype 3 or HIV coinfection, but had more frequent comorbidities and drug consumption. Half of the patients had cirrhosis, whatever their ages. The main treatment regimens were sofosbuvir/ledipasvir (37.8%), sofosbuvir/daclatasvir (31.8%), sofosbuvir/simeprevir (16.9%), sofosbuvir/ribavirin (7.8%); ribavirin was given to 24% of patients. The overall sustained virological response (SVR) rate was 91.0 % (95% CI: 89.292.5%) with no difference according to age. Logistic regression of the independent predictors of SVR were albumin, hepatocellular carcinoma and treatment regimen, but not age. The rate of severe adverse events (66 in 59/1062 [5.6%] patients) tended to be greater in patients older than 64 years of age (21/261,8.1%), but the only independent predictors of SAE by logistic regression were cirrhosis and baseline hemoglobin. Patient-reported overall tolerance was excellent in all age groups, and patient-reported fatigue decreased during and after treatment, independent of age.
The high efficacy and tolerance of interferon-free regimens is confirmed in elderly patients in real-life conditions.
The elderly and direct antiviral agents: Constraint or challenge?
2017, Digestive and Liver Disease
Citation Excerpt :
Conversely, lower levels of efficacy were found by Conti et al. [12], probably due to the large presence of advanced cirrhotic patients in their study population. As expected, moreover, a lower SVR-12 rate was demonstrated in patients aged >60 years treated with a SIM/IFN-based regimen [13]. In addition to the mere achievement of SVR, other important aspects should be considered when evaluating the outcome of DAAs treatment in elderly.
Direct antiviral agents (DAAs) for chronic hepatitis C showed great effectiveness and good safety profile. So far, few data are available about their use in elderly subjects.
To assess management, safety and outcome of DAAs treatments in the elderly.
This retrospective, single-centre study enrolled all patients aged ≥65 years, compared by age (group A: 65–74 years, group B: ≥75 years), who completed DAAs between February 2015–November 2016. Variables potentially associated to adverse events (AEs) were analyzed. Sustained virological response (SVR) was evaluated at 12-weeks follow-up.
DAAs were administered to 221 patients aged ≥65 years (males: 112; group A: 130, group B: 91). Prescribed regimens were: sofosbuvir-based: 44 patients (19.9%), simeprevir-based: 25 (15%), ledipasvir-based: 49 (22.2%), daclatasvir-based: 12 (5.4%), paritaprevir/ritonavir + ombitasvir ± dasabuvir: 91 (41.2%). Ribavirin was used in 121 patients. In 58 subjects co-medications were adjusted due to drug interactions. At least one AE occurred in 130 patients, including 13 SAEs, mainly in older subjects (p = 0.04). Female sex (p = 0.04), liver stiffness (p = 0.023), use of simeprevir (p = 0.03) and ribavirin (p = 0.009) were associated with AEs. SVR-12 was achieved in 96,9% of subjects.
A careful baseline evaluation and a strict monitoring allow to optimise management and outcome of DAAs in elderly.
Efficacy and safety of direct-acting antiviral therapy for hepatitis C virus in elderly patients (≥65 years old): A systematic review and meta-analysis
2022, Journal of Viral Hepatitis

View all citing articles on Scopus

View full text

Short communicationReal life experience with direct-acting antivirals agents against hepatitis C infection in elderly patients

Highlights

Abstract

Background

Objectives

Study design

Results

Conclusions

Graphical abstract

Section snippets

Backgorund

Objectives

Study design

Results

Discussion

Conflicts of interest

Funding

Ethical approval

Acknowledgments

J. Hepatol.

Clin. Gastroenterol. Hepatol.

J. Hepatol.

Hepatitis C

Epidemiology and natural history of HCV infection

Nat. Rev. Gastroenterol. Hepatol.

Prevalence of hepatitis C virus infection in the general population of northern Spain

Eur. J. Gastroenterol. Hepatol.

Seroprevalence of HCV and HIV infections by year of birth in Spain: impact of US CDC and USPSTF recommendations for HCV and HIV testing

PLoS One

The prevalence of hepatitis A, B and C viral markers in the population of Gijón between 26 and 65 years old

Gastroenterol. Hepatol.

Short communication
Real life experience with direct-acting antivirals agents against hepatitis C infection in elderly patients