Treatment Discontinuation, Adherence, and Real-World Effectiveness Among Patients Treated with Harvoni (Ledipasvir/Sofosbuvir) in the United States

Treatment Discontinuation, Adherence, and Real-World Effectiveness Among Patients Treated with Ledipasvir/Sofosbuvir in the United States
Amy Puenpatom Michael Hull Jeffrey McPheeters Kay Schwebke

First Online: 04 July 2017

Received: 01 June 2017
DOI: 10.1007/s40121-017-0163-0

Full Text Article Online

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Abstract
Introduction
Ledipasvir/sofosbuvir (LDV/SOF) for hepatitis C virus (HCV) treatment provides an oral interferon-free treatment regimen with high rates of sustained virologic response (SVR). This study assessed treatment discontinuation, factors associated with treatment completion, and real-world effectiveness.

Methods
Patients with HCV treated with LDV/SOF between October 2014 and June 2015 and enrolled in a large US health plan were identified. Expected treatment duration was calculated based on IDSA/AASLD treatment guidelines and US labels using data for genotype, initial treatment regimen, baseline cirrhosis, and prior treatments. Logistic regression was used to identify factors associated with treatment completion, controlling for patient characteristics.

Results
The study included 1483 LDV/SOF patients. Mean age was 59.7 years, most were male (63.9%), had commercial insurance (51.9%), and were treatment-naïve (85.6%). Cirrhosis or end stage liver disease was present in 46.1%. Among patients with an expected 8-week treatment regimen, 49.4% were treated for longer. Most patients (99.8%) with expected 12-week treatment durations were adherent to the expected treatment duration. Treatment-experienced patients [odds ratio (OR) 0.124, p < 0.001] and those on Medicare (OR 0.382, p = 0.039) had lower odds of completing the expected treatment regimen, while males were more likely to complete treatment than females (OR 3.235, p = 0.003). SVR12 in patients treated with LDV/SOF was 89.4% (n = 76/85).

Conclusion
Half of patients eligible for an 8-week treatment regimen with LDV/SOF were treated longer, while most patients with a 12-week regimen were adherent to the expected treatment duration. Prior HCV treatment, female gender, and Medicare Advantage insurance were associated with lower odds of treatment completion. Overall SVR12 was 89.4%.
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Hepatitis C cases on the rise with millennials

Hepatitis C cases on the rise with millennials

By Sabra Stafford

The ongoing opioid crisis in the nation has created another consequence for healthcare providers as data reveals a growing number of hepatitis C infections among young adults.

New data released recently by the California Department of Public Health show an increase in newly reported hepatitis C cases among young adults in the state. Between 2007 and 2015, newly reported hepatitis C infections increased 55 percent among men 20-29 years of age and 37 percent among women in the same age group.

The rates are consistent with increases in hepatitis C across the country.

Continue reading....

Hepatitis B and C virus infection and diabetes mellitus: A cohort study

Recommended Reading
Improvement in Glycemic Control of Type2 Diabetes After Successful Treatment of Hepatitis C Virus
Diabetes Care Publish Ahead of Print, published online June 28, 2017
Hepatitis C virus (HCV)infection is associated with diabetes and may worsen glycemic control in patients with diabetes. We aimed to investigate whether eradication of HCV infection with direct-acting antiviral(DAAs) agents is associated with improved glycemic control in patients with diabetes.
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The above article link provided by Henry E. Chang via Twitter.
I highly suggest you follow Henry E. Chang on Twitter if you are interested in reading full text articles about the treatment and management of hepatitis C.

Hepatitis B and C virus infection and diabetes mellitus: A cohort study

Yun Soo Hong, Yoosoo Chang, Seungho Ryu, Miguel Cainzos-Achirica, Min-Jung Kwon, Yiyi Zhang, Yuni Choi, Jiin Ahn, Sanjay Rampal, Di Zhao, Roberto Pastor-Barriuso, Mariana Lazo, Hocheol Shin, Juhee Cho & Eliseo Guallar

doi:10.1038/s41598-017-04206-6

Received: 02 February 2017
Accepted: 10 May 2017
Published online:04 2017

Link
Full Text

Abstract
The role of hepatitis virus infection in glucose homeostasis is uncertain. We examined the associations between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the development of diabetes in a cohort (N = 439,708) of asymptomatic participants in health screening examinations. In cross-sectional analyses, the multivariable-adjusted odds ratio for prevalent diabetes comparing hepatitis B surface antigen (HBsAg) (+) to HBsAg (−) participants was 1.17 (95% CI 1.06–1.31; P = 0.003). The corresponding odds ratio comparing hepatitis C antibodies (HCV Ab) (+) to HCV Ab (−) participants was 1.43 (95% CI 1.01–2.02, P = 0.043). In prospective analyses, the multivariable-adjusted hazard ratio for incident diabetes comparing HBsAg (+) to HbsAg (−) participants was 1.23 (95% CI 1.08–1.41; P = 0.007). The number of incident cases of diabetes among HCV Ab (+) participants (10 cases) was too small to reliably estimate the prospective association between HCV infection and diabetes. In this large population at low risk of diabetes, HBV and HCV infections were associated with diabetes prevalence and HBV infection with the risk of incident diabetes. Our studies add evidence suggesting that diabetes is an additional metabolic complication of HBV and HCV infection.

Introduction
Chronic viral hepatic infections are a major threat to public health worldwide. Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) are the leading causes of cirrhosis and hepatocellular carcinoma, two conditions with increasing mortality and burden of disease especially in the developing countries1, 2. As the liver has a key role in glucose metabolism and adequate liver function is essential to maintain glucose homeostasis3, 4, diabetes may be a complication of end-stage liver disease, especially in patients with chronic HCV infection4,5,6,7. Since diabetes is another major concern in public health, it is very important to establish if chronic viral hepatitis is associated with an increased risk of diabetes prior to the development of end-stage liver disease.

The association between positive serology for hepatitis B surface antigen (HBsAg) and incident diabetes has been studied in only a few longitudinal studies^{5, 8, 9}, that found no significant associations. Cross-sectional studies have also shown no association between positive serology for HBsAg and diabetes^{10, 11}, although the number of participants in these studies was small and they had varying degrees of HBV-related liver disease. On the other hand, the presence of HCV antibodies (HCV Ab) appears to increase the risk of both incident and prevalent diabetes^{6, 7, 10,11,12,13,14}, although many of these studies were not prospective^{6, 7, 11, 14}, had small sample sizes^{7, 12, 13}, or included cases with liver cirrhosis which, by itself, can increase the risk of diabetes¹⁴. We thus examined the prospective association between HBsAg (+) or HCV Ab (+) and incident diabetes in a large cohort of asymptomatic subjects who participated in health screening examinations. In addition to the prospective associations, we also evaluated the cross-sectional associations of hepatitis virus infection and prevalent diabetes at baseline for comparability with previous studies.

Full Text Available Online
Nature's scientific reports

http://www.nature.com/articles/s41598-017-04206-6?WT.feed_name=subjects_immunology

Australian NSP Survey National Data Report - Nationally initiation of HCV treatment increased in 2016

Australian NSP Survey National Data Report 2012 – 2016

Download The Survey

Description 

The Australian Needle and Syringe Program Survey (ANSPS) provides serial point prevalence estimates of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) antibodies and sexual and injecting risk behaviour among people who inject drugs (PWID) in Australia. Conducted annually over a one-two week period in October, all clients attending participating needle and syringe program (NSP) services are invited to complete a brief, anonymous questionnaire and to provide a capillary blood sample for HIV and HCV antibody testing.

This report presents national and state/territory data for the period 2012 to 2016.

Key findings 

• In 2016, 50 Australian Needle and Syringe Programs (NSPs) participated in the ANSPS and 2,210 NSP attendees completed the survey. The response rate was 41%.
• Over the period 2012 to 2016, the median age of survey respondents increased from 38 years to 42 years, with a concurrent decrease in the proportion of young injectors (aged <25 years) from 7% in 2012 to 4% in 2016.
• HIV antibody prevalence remained low and stable nationally, ranging from 1.2% to 2.1% over the period 2012 to 2016
• Hepatitis C virus (HCV) antibody prevalence was stable over the period 2012 to 2016, ranging from 51% to 57%.
• Nationally, the proportion of respondents who reported recent (last 12 months) initiation of HCV treatment was low and stable at 1-3% between 2011-2015, but increased significantly to 22% in 2016, with substantial increases observed in all jurisdictions.

Source

https://kirby.unsw.edu.au/report/australian-nsp-survey-national-data-report-2012-2016

Sustained response to direct-acting HCV antivirals tied to lower HCC risk

Sustained response to direct-acting HCV antivirals tied to lower HCC risk

July 3, 2017

By Marilynn Larkin
NEW YORK (Reuters Health) - A sustained virologic response to direct-acting antiviral treatment of hepatitis C (HCV) is associated with a “considerable” reduction in the risk of hepatocellular carcinoma (HCC), researchers say.

Dr. Fasiha Kanwal of Baylor College of Medicine in Houston, Texas and colleagues analyzed data on 22,500 HCV patients (mean age 62) from 129 Veterans Health Administration hospitals who filled more than one prescription of sofosbuvir, simeprevir, ledipasvir, a combination of paritaprevir/ritonavir or ombitasvir and dasabuvir, and daclatasvir in 2015...
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Recommended Reading
Updated data investigating the possible risk of developing liver cancer (hepatocellular carcinoma, or HCC) during and after direct-acting antiviral therapy in patients with hepatitis C.

Liver Cancer After Treatment For Hepatitis C
​Research demonstrates that while SVR markedly reduced liver-related complications and liver cancer, some long-term risk for liver cancer remained in those who were cured of Hepatitis C. But after direct-acting antiviral therapy does the risk of developing liver cancer increase?

Hepatitis C Therapies Perform Well in Challenging Patients

Medscape Coverage from
Digestive Disease Week (DDW) 2017

Hepatitis C Therapies Perform Well in Challenging Patients
William F. Balistreri, MD

At this year's Digestive Disease Week, several studies looked into the nuances of treating hepatitis C virus (HCV)infection. Of particular interest were new data regarding difficult-to-treat groups and the validation of shorter, simpler regimens

Glecaprevir and PibrentasvirIn several phase 2 and 3 clinical trials, patients who received the pangenotypic direct-acting antivirals (DAAs) glecaprevir (GLE) and pibrentasvir (PIB) achieved sustained virologic response (SVR) rates of 92%-100% across all six major HCV genotypes...

Sofosbuvir/Velpatasvir/Voxilaprevir
A pangenotypic combination of sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) was designed to inhibit three distinct HCV targets: the NS5B polymerase, the NS5A protein, and NS3/4A protease, respectively.

Flamm and colleagues^[3] presented cumulative data from 1056 patients with and without compensated cirrhosis who were infected with HCV genotype 1-6 and treated with the once-daily fixed-dose combination tablet of SOF/VEL/VOX in phase 3 studies....

Continue reading....

Free registration required

Weekend Reading: July Hep C Newsletters & Rebuttal over Cochrane Review of DAAs

July Hep C Newsletters & Headlines
Welcome folks, here is this months index of wonderful newsletters filled with invaluable information about viral hepatitis.

In The News
It's always great when the media is alive with news about HCV, right? Well, maybe not in this case. The HCV community was blindsided last month when an article with a somewhat "clickbait" headline was released by The Guardian.

The Article
The Guardian reported on a systematic review published by the Cochrane Collaboration that suggested achieving SVR (cure) for patients using hepatitis C direct-acting antivirals (DAAs) doesn't correlate with any long term benefits.

So what's the good news? Thanks to social media both the Guardian article and Cochrane review was highly debated on Twitter, organized nicely by Henry E. Chang.

The Rebuttal - It Started On Twitter

Tweeted by Henry E. Chang

Reactions from Hepatitis C Community on a Recent Cochrane Review of DAAs
Cochrane Review Group's fallacious conclusions are missing real issue of access to effective and highly curative therapy for chronic HCV infection. Irresponsible reporting by news media of the results risks even more harm than the original review.
Begin here....

A special thanks to Henry E. Chang for sending us to each rebuttal and all ongoing media coverage.

The Real News

The European Association for the Study of the Liver (EASL) published a response to the Cochrane Systematic Review, as did the Lancet on June 22, and more recently in the July issue of the Lancet. The American Association for the Study of Liver Diseases (AASLD) and Infectious Diseases Society of America (IDSA) put out this statement. In Australia a joint Position Statement was released by Australian Health Organisations urging medical professionals and patients not to be influenced by the report. In addition Hepatitis C Trust responded with concern over media coverage, citing the Guardian article. Published under letters on 13 June 2017, the Guardian published: Hepatitis C antiviral drugs are effective, with this subtitle, The Cochrane analysis casting doubt on this life-saving therapy is flawed and may deter patients from seeking it, say clinicians and scientists. Lucinda K. Porter, explained Cochrane’s findings in an easy to read article: Horrendous Hepatitis Headlines.  Published over at MD Blog at the end of June experts elaborate on improvement of underlying fibrosis to extrahepatic manifestations following SVR, here is the article: The Cochrane Review Conclusion for Hepatitis C DAA Therapies is Wrong.

In the weeks following the Cochrane review, Sony Salzman from MedPage Today wrote about the show of support from the medical community and advocates; Hep C Experts Condemn Cochrane Review Dissing Direct Antivirals. Here is an excerpt:

Research demonstrates that while SVR markedly reduced liver-related complications and liver cancer, some long-term risk for liver cancer remained in those who were cured of Hepatitis C. But after direct-acting antiviral therapy does the risk of developing liver cancer increase?

Continue reading...

More Recent Commentary:
HIV and ID Observations
July 19th, 2017
Mystifying Cochrane Library Review on HCV Therapy Elicits Strong Response from IDSA
Last month, The Cochrane Review published a controversial paper on HCV therapy that left many ID doctors and hepatologists rather perplexed.
After reviewing 138 randomized clinical trials using directly acting, non-interferon based therapies, they came to the following conclusions:

• The use of sustained virologic response (“SVR”) — or “cure”, if you want to use plain English — as a valid endpoint for clinical outcomes is questionable.
• There is insufficient evidence that treatment with DAA-based regimens improves clinical outcome.
• The studies reviewed were at high risk of bias, so tended to overestimate benefits and minimize harm.
• More randomized clinical trials are needed.

Anyone — clinician, researcher, or patient — who has experienced the miraculous advances in HCV therapy that started in 2014 could easily be scratching their heads at these conclusions.
The FDA might be surprised as well, since they have allowed permanent clearance of HCV RNA as an appropriate surrogate marker of the effectiveness of HCV therapy.
Fortunately, we now have a focused, persuasive response by the IDSA, just published in Clinical Infectious Diseases; Download PDF here....
Continue reading.......

HCV NEXT

IDSA, AASLD critical of Cochrane review of HCV drugs
July 26, 2017
The IDSA and AASLD wrote a joint response, which was published in Clinical Infectious Diseases, to the Cochrane review that concluded that direct-acting antiviral (DAA) drugs have not been shown to reduce risks for HCV-related morbidity or all-cause mortality. The review also claimed that prior trials have underestimated DAA adverse effects.
Continue reading....

Australia - Podcast

The Cochrane Collaboration assessment of hepatitis C drug trials comes under review from our resident hep C expert Carla Treloar, while Annie Madden digs deeper into the drug decriminalisation debate as the World Health Organisation and the United Nations wade into the debate.



Now lets move on to those great July newsletters.

New On The Blog July 25:
Hepatitis Updates: Research and News From Around The Web

Welcome to a mix of research, blog updates and news about hepatitis C you may have missed over the last week.

The New York City Hepatitis C Task Force

The New York City Hepatitis C Task Force is a city-wide network of service providers and advocates concerned with hepatitis C and related issues. The groups come together to learn, share information and resources, network, and identify hepatitis C related needs in the community. Committees form to work on projects in order to meet needs identified by the community.

July Updates
Email Campaign Archive

HCV Action

HCV Action brings together hepatitis C health professionals from across the patient pathway with the pharmaceutical industry and patient representatives to share expertise and good practice.

HCV Action e-update

05 Jul 2017

Weekly Bull

HepCBC is a non-profit organization run by and for people infected and affected by hepatitis C. Our mission is to provide education, prevention and support to those living with HCV.

Latest Issue: Weekly Bull

HCV Advocate
The HCV Advocate newsletter is a valuable resource designed to provide the hepatitis C community with monthly updates on events, clinical research, and education.

July Issue

International Liver Conference – Part 3 – Third Time’s the Charm – This is our final coverage in the HCV Advocate newsletter.

Begin here....

Hep Magazine

Hep is an award-winning print and online brand for people living with and affected by viral hepatitis. Offering unparalleled editorial excellence since 2010, Hep and Hep Magazine are the go-to source for educational and social support for people living with hepatitis.

Hep Summer 2017 - Special Issue

Excellent Treatments, Still Room for Improvement

An analysis of forty-two clinical trials of all the approved direct acting antiviral HCV regimens.

Begin here..

GI & Hepatology News

Over 17,000 gastroenterologists and hepatologists rely on GI & Hepatology News every month to cover the world of medicine with breaking news, on-site medical meeting coverage, and expert perspectives both in print and online. The official newspaper of the AGA Institute was launched in partnership with IMNG in January 2007.

View all newsletters, here.

Hepatitis B and C Public Policy Association

The Association’s Newsletter covers clinical, epidemiological and policy developments in the field of HBV and HCV.

June Issue

British Liver Trust
The British Liver Trust is the leading UK liver disease charity for adults – we provide information and support; increase awareness of how liver disease can be prevented and promote early diagnosis; fund and champion research and campaign for better services.

Latest Newsletter

At the moment three quarters of people are diagnosed with liver disease in a hospital setting when they already have cirrhosis – which can be too late. Love Your Liver aims to change this by raising awareness of the risk factors of liver disease and improving early diagnosis...
Begin here..

NNAAPC-HCV

The National Native American AIDS Prevention Center (NNAAPC), located in Denver, Colorado, was incorporated in 1987 by a network of concerned Native people who advocated and promoted the need for HCV/HIV/AIDS prevention education created by and for Native communities.  NNAAPC has also worked in the area of Hepatitis C since 1995 and is continuing to develop prevention activities and efforts to fight this “silent epidemic” in Native communities.

Eliminating Hepatitis C in American Indian and Alaskan Native Communities: Focus on Price of Medications

Begin here...

Healthy You

For Your Viewing Pleasure
The Liver - Super Foods & Supplements and Patient Friendly Video On Managing Medications With Liver Disease & Cirrhosis

NIH News in Health

Check out the July issue of NIH News in Health, the monthly newsletter bringing you practical health news and tips based on the latest NIH research.

Struggling to Sleep?

Most people who have breathing pauses while asleep, or sleep apnea, don’t realize it. It can leave you tired and put your health at risk.

Free eBooks on Health

Looking for free eBooks about the brain, stroke, low back pain, dementia, or other health topics? These and many other topics are available in formats that work with eBook readers, tablets, and smart phones.
Begin here...

ACP Internist

Current Issue

July/August 2017

Prediabetes: What can doctors call it?

Internists know to screen patients for diabetes, but may be unsure how to manage patients whose blood glucose levels are higher than normal but fall below the cutoff of the disease.

Begin here...

New Online

Clinical Liver Disease (CLD) just launched; Pangenotypic regimens and the next generation hepatitis C virus therapy a multimedia overview of: Three new antiviral therapies for viral hepatitis C  anticipated in the next several months: GP, glecaprevir (protease inhibitor [PI])/pibrentasvir (NS5A inhibitor); SOF/VEL/VOX, sofosbuvir (NS5B inhibitor)/velpatasvir (NS5A)/voxilaprevir (NS3); and MK3, grazoprevir (NS3) + MK-3682 (NS5B) + NS5A inhibitor (elbasvir or Ruzasvir). 
Begin here...

Enjoy the holiday weekend!

Tina

Evaluating a Collaborative Approach to Improve Prior Authorization Efficiency in the Treatment of Hepatitis C Virus

Evaluating a Collaborative Approach to Improve Prior Authorization Efficiency in the Treatment of Hepatitis C Virus

Dunn, Emily E. PharmD; Vranek, Kathryn PharmD; Hynicka, Lauren M. PharmD, BCPS; Gripshover, Janet CRNP; Potosky, Darryn MD; Mattingly, T. Joseph II PharmD,

MBAQuality Management in Health Care: July/September 2017 - Volume 26 - Issue 3 - p 136–139 doi: 10.1097/QMH.0000000000000137

Objective: A team-based approach to obtaining prior authorization approval was implemented utilizing a specialty pharmacy, a clinic-based pharmacy technician specialist, and a registered nurse to work with providers to obtain approval for medications for hepatitis C virus (HCV) infection.

The objective of this study was to evaluate the time to approval for prescribed treatment of HCV infection.

Methods: A retrospective observational study was conducted including patients treated for HCV infection by clinic providers who received at least 1 oral direct-acting antiviral HCV medication. Patients were divided into 2 groups, based on whether they were treated before or after the implementation of the team-based approach. Student t tests were used to compare average wait times before and after the intervention.

Results: The sample included 180 patients, 68 treated before the intervention and 112 patients who initiated therapy after. All patients sampled required prior authorization approval by a third-party payer to begin therapy. There was a statistically significant reduction (P = .02) in average wait time in the postintervention group (15.6 ± 12.1 days) once adjusted using dates of approval.

Conclusions: Pharmacy collaboration may provide increases in efficiency in provider prior authorization practices and reduced wait time for patients to begin treatment.

Continue to full text article online