High adherence to all-oral directly acting antiviral HCV therapy among an inner-city patient population in a phase 2a study

Petersen, Tess; Townsend, Kerry; Gordon, Lori A.; Sidharthan, Sreetha; Silk, Rachel; Nelson, Amy; Gross, Chloe; Calderón, Mónica; Proschan, Michael A.; Osinusi, Anu; Polis, Michael A.; Masur, Henry; Kottilil, Shyam; Kohli, Anita

doi:10.1007/s12072-015-9680-7

Cited by 61 publications

(81 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further research suggests that while adherence to DAA regimens is high overall, it diminishes with longer treatment courses, particularly between weeks 8 and 12, among people with hepatitis C genotype 1 and people coinfected with hepatitis C and HIV 20,21. Older patients with a high number of comorbidities are also more likely to be nonadherent 22.…”

Section: Medication Adherence In a Chronic Disease Settingmentioning

confidence: 99%

The Australasian Hepatology Association consensus guidelines for the provision of adherence support to patients with hepatitis C on direct acting antivirals

Richmond¹,

Sheppard‐Law²,

Mason³

et al. 2016

PPA

View full text Add to dashboard Cite

BackgroundHepatitis C is a blood-borne virus primarily spread through sharing of drug-injecting equipment. Approximately 150 million people worldwide and 230,000 Australians are living with chronic hepatitis C infection. In March 2016, the Australian government began subsidizing direct acting antivirals (DAAs) for the treatment of hepatitis C, which are highly effective (95% cure rate) and have few side effects. However, there is limited evidence to inform the provision of adherence support to people with hepatitis C on DAAs including the level of medication adherence required to achieve a cure.MethodologyIn February 2016, a steering committee comprising four authors convened an expert panel consisting of six hepatology nurses, a hepatologist, a pharmacist, a consumer with hepatitis C and treatment experience, and a consumer advocate. The expert panel focused on the following criteria: barriers and enablers to DAA adherence; assessment and monitoring of DAA adherence; components of a patient-centered approach to DAA adherence; patients that may require additional adherence support; and interventions to support DAA adherence. The resultant guidelines underwent three rounds of consultation with the expert panel, Australasian Hepatology Association (AHA) members (n=12), and key stakeholders (n=7) in June 2016. Feedback was considered by the steering committee and incorporated if consensus was achieved.ResultsTwenty-four guidelines emerged from the evidence synthesis and expert panel discussion. The guidelines focus on the pretreatment assessment and education, assessment of treatment readiness, and monitoring of medication adherence. The guidelines are embedded in a patient-centered approach which highlights that all patients are at risk of nonadherence. The guidelines recommend implementing interventions focused on identifying patients’ memory triggers and hooks; use of nonconfrontational and nonjudgmental language by health professionals; and objectively monitoring adherence.ConclusionThese are the first guidelines to support patients and health professionals in the delivery of clinical care by identifying practical adherence support interventions for patients taking DAAs.

show abstract

Section: Medication Adherence In a Chronic Disease Settingmentioning

confidence: 99%

The Australasian Hepatology Association consensus guidelines for the provision of adherence support to patients with hepatitis C on direct acting antivirals

Richmond¹,

Sheppard‐Law²,

Mason³

et al. 2016

PPA

View full text Add to dashboard Cite

show abstract

“…Previous analyses of DAA regimens have demonstrated high adherence to treatment in the overall chronic HCV‐infected patient population, including those who were on opioid substitution therapy (OST) and people who use drugs (≥95% and ≥90% respectively). Some studies have suggested that adherence to DAA therapy decreases with increased treatment duration . In a pooled analysis of 4825 chronic HCV‐infected patients from 13 trials receiving 8‐24 weeks of HCV antiviral therapy, a longer treatment duration was associated with a lower likelihood of adherence (odds ratio [OR]: 0.98 for each additional week; P = .002) .…”

Section: Introductionmentioning

confidence: 99%

Adherence to pan‐genotypic glecaprevir/pibrentasvir and efficacy in HCV‐infected patients: A pooled analysis of clinical trials

Brown

Welzel

Conway

et al. 2019

Liver International

View full text Add to dashboard Cite

Background & Aims Adequate adherence to hepatitis C virus (HCV) treatment is believed to be a key component of treatment success because non‐adherence can potentially result in treatment failure and the emergence of resistant viral variants. This analysis assessed factors associated with non‐adherence to glecaprevir/pibrentasvir (G/P) therapy and the impact of non‐adherence on sustained virological response at post‐treatment week 12 (SVR12) rates in HCV genotype (GT) 1‐6‐infected patients. Methods Adherence was calculated by pill counts at study visits during treatment, and defined as having a lowest treatment adherence of ≥80% and ≤120% at each study visit. Exploratory logistic regression modelling assessed predictors of non‐adherence to G/P therapy. SVR12 rates by treatment adherence were assessed in the intent‐to‐treat (ITT) population and modified ITT (mITT) population, which excludes non‐virological failures. Results Overall, 97% (2024/2091) of patients were adherent to G/P therapy at all consecutive study visits. Alcohol use was the only baseline characteristic independently associated with non‐adherence to G/P therapy (OR: 2.38; 95% CI: 1.13‐5.01; P = .022). In the mITT population, overall SVR12 rates were high both in patients who were adherent to G/P therapy and those who were not (99% [1983/2008] and 95% [58/61] respectively; P = .047). Corresponding SVR12 rates in the ITT population were 98% (1983/2024) and 87% (58/67) respectively. Conclusions Most patients adhered to G/P therapy. SVR12 rates were high both in patients who were adherent to G/P treatment and those who were not. Patient education on treatment adherence should remain an important part of HCV treatment. Clinical trials registration NCT02604017, NCT02640482, NCT02640157, NCT02636595, NCT02642432, NCT02651194, NCT02243293, NCT02446717.

show abstract

“…It has been suggested that the high SVR12 rates achieved with nucleotide‐based 3‐DAA regimens following a shortened treatment duration of 6 or 8 weeks may be partly ascribed to the more rapid first‐phase decline in HCV ribonucleic acid (RNA) observed when a third DAA was added . In addition to the high levels of therapeutic efficacy achieved with 2‐ or 3‐DAA regimens, the opportunity to provide patients with an effective shorter course of therapy could also have a favorable impact on affordability, adherence, and patient quality of life due to reduced side effects and decreased pill burden …”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, safety, and tolerability of the 2‐ and 3‐direct‐acting antiviral combination of AL‐335, odalasvir, and simeprevir in healthy subjects

Kakuda¹,

McClure²,

Westland³

et al. 2018

Pharmacology Res & Perspec

View full text Add to dashboard Cite

This Phase I, open‐label, two‐group, fixed‐sequence study evaluated the pharmacokinetics and safety of AL‐335, odalasvir, and simeprevir in healthy subjects. Group 1 (n = 16) received AL‐335 800 mg once daily (QD) (days 1‐3, 11‐13, and 21‐23), simeprevir 150 mg QD (days 4‐23), and odalasvir 150 mg (day 14) followed by 50 mg QD (days 15‐23). Group 2 (n = 16) received the same AL‐335 regimen as in Group 1 plus odalasvir 150 mg (day 4) followed by 50 mg QD (days 5‐23) and simeprevir 150 mg QD (days 14‐23). Blood samples were collected to determine plasma concentrations of AL‐335 (prodrug) and its metabolites, ALS‐022399 (monophosphate precursor) and ALS‐022227 (parent nucleoside), odalasvir, and simeprevir. Thirty‐two subjects were enrolled. Odalasvir and simeprevir given alone, or in combination, increased AL‐335 area under plasma concentration‐time curve over 24 hours (AUC 0‐24 h) 3‐, 4‐, and 7‐ to 8‐fold, respectively; ALS‐022399 AUC 0‐24 h increased 2‐, 2‐, and 3‐fold, respectively. Simeprevir had no effect on ALS‐022227 AUC 0‐24 h, whereas odalasvir with/without simeprevir increased ALS‐022227 AUC 0‐24 h 1.5‐fold. AL‐335 had no effect on odalasvir or simeprevir pharmacokinetics. Odalasvir and simeprevir AUC 0‐24 h increased 1.5‐ to 2‐fold for both drugs when coadministered irrespective of AL‐335 coadministration. Study medications were well tolerated with no serious adverse events. One subject prematurely discontinued study drugs (unrelated event). This study defined the preliminary pharmacokinetic and safety profiles of the combination of AL‐335, odalasvir, and simeprevir in healthy subjects. These data support the further evaluation of this combination for the treatment of chronic hepatitis C virus infection.

show abstract

High adherence to all-oral directly acting antiviral HCV therapy among an inner-city patient population in a phase 2a study

Cited by 61 publications

References 24 publications

The Australasian Hepatology Association consensus guidelines for the provision of adherence support to patients with hepatitis C on direct acting antivirals

The Australasian Hepatology Association consensus guidelines for the provision of adherence support to patients with hepatitis C on direct acting antivirals

Adherence to pan‐genotypic glecaprevir/pibrentasvir and efficacy in HCV‐infected patients: A pooled analysis of clinical trials

Pharmacokinetics, safety, and tolerability of the 2‐ and 3‐direct‐acting antiviral combination of AL‐335, odalasvir, and simeprevir in healthy subjects

Contact Info

Product

Resources

About