Friday, May 26, 2017

Do HCV DAAs Increase HCC Recurrence Risk or Not?

Published in Clinical Thought

Do HCV DAAs Increase HCC Recurrence Risk or Not?
Paul Y. Kwo, MD - 5/25/2017
More from this author
Does the administration of direct-acting antiviral (DAA) therapy increase a patient’s risk of hepatocellular carcinoma (HCC) recurrence?

Recent data presented at EASL 2017 from Reig and colleagues extended their previous findings of an unexpectedly high rate of HCC recurrence following previous complete response to resection, ablation, or transarterial chemoembolization in the DAA era. Of 77 patients who initiated DAA therapy after presumed control of HCC, confirmed by radiologic assessment, 24 (31.2%) developed recurrence of HCC. Most individuals were Child-Pugh A (86%) and BCLC 0/A stage (97%).
Continue reading....

MedPage Today
Published in AGA Reading Room      

New Hep C Treatment Not Linked to Liver Cancer
by Liz Highleyman
Contributing Writer, MedPage Today
5/25/2017
Contrary to some earlier research, most recent studies see no association between response to DAAs and HCC.

Most Researchers Find No Link
The Barcelona group stood alone among several other research groups presenting at the EASL meeting that did not see an increased risk of HCC after taking into account other factors including liver disease severity:
  • Etienne Audureau from Henri Mondor University Hospital in Paris reported that lack of SVR -- not the type of treatment -- was the strongest predictor of liver cancer in cirrhotic patients; older age, alcohol use, and impaired liver function also predicted HCC
  • Hamish Innes from Glasgow Caledonian University said that HCC risk following SVR was associated with baseline patient risk factors, but not DAA use; in a multivariate analysis, HCC risk was similar for patients treated with either DAAs or interferon
  • Dong Ji from the Hong Kong Humanity and Health Medical Center in Beijing reported no increase in HCC incidence among patients cured with DAAs compared with interferon
  • Masaaki Korenaga from Kohnodai Hospital in Japan said that SVR after treatment with sofosbuvir/ledipasvir (Harvoni) led to a reduction in HCC incidence, similar to the drop seen in patients cured with interferon
  • Vincenza Calvaruso from the University of Palermo in Sicily reported no increase in the development of new HCC among patients who achieved SVR with DAAs, compared with those cured with interferon
Continue reading.......

Recommended 
Liver Cancer After Treatment For Hepatitis C
A collection of research articles investigating the possible risk of developing liver cancer (hepatocellular carcinoma, or HCC) during and after direct-acting antiviral therapy in patients with hepatitis C. 

Healio - Two DAA regimens produce high SVR12 rates in HCV genotype 4

Top Story
Two DAA regimens produce high SVR12 rates in HCV genotype 4
May 26, 2017
Treatment with Technivie plus ribavirin or Harvoni plus ribavirin were effective in patients with hepatitis C genotype 4, according to a recently published study.

“Worldwide, an estimated 15 million people are infected with hepatitis C virus (HCV) genotype 4 (GT 4). Because there is only moderate response to interferon-based therapy in these patients, this infection has been considered more difficult to treat,” the researchers wrote. “Although scarcer than for GT 1 patients, data from clinical trials on the efficacy of direct-acting antiviral agents (DAAs) in GT 4 patients suggest that interferon-free regimens with DAAs have the potential to achieve high rates of sustained virologic response (SVR) in GT 4 patients.”

Reference
Real-World Effectiveness and Safety of Oral Combination Antiviral Therapy for Hepatitis C Virus Genotype 4 Infection

Current therapy for chronic hepatitis C: The role of direct-acting antivirals.


Antiviral Res. 2017 Jun;142:83-122. doi: 10.1016/j.antiviral.2017.02.014. Epub 2017 Feb 24.

Current therapy for chronic hepatitis C: The role of direct-acting antivirals.
Li G1, De Clercq E2.

Read Full Text Article

Abstract
One of the most exciting developments in antiviral research has been the discovery of the direct-acting antivirals (DAAs) that effectively cure chronic hepatitis C virus (HCV) infections. Based on more than 100 clinical trials and real-world studies, we provide a comprehensive overview of FDA-approved therapies and newly discovered anti-HCV agents with a special focus on drug efficacy, mechanisms of action, and safety. We show that HCV drug development has advanced in multiple aspects: (i) interferon-based regimens were replaced by interferon-free regimens; (ii) genotype-specific drugs evolved to drugs for all HCV genotypes; (iii) therapies based upon multiple pills per day were simplified to a single pill per day; (iv) drug potency increased from moderate (∼60%) to high (>90%) levels of sustained virologic responses; (v) treatment durations were shortened from 48 to 12 or 8 weeks; and (vi) therapies could be administered orally regardless of prior treatment history and cirrhotic status. However, despite these remarkable achievements made in HCV drug discovery, challenges remain in the management of difficult-to-treat patients.

Highlights
• HCV genotype-specific drugs evolve to pan-genotypic drugs.
• Drug potency increases from moderate (∼60%) to high (>90%) levels of sustained virologic response.
• Treatment durations are shortened from a 48-week to 12-week or 8-week period.
• HCV therapies based upon multiple pills per day are simplified to a single pill per day.
• HCV therapies are administered orally regardless of prior treatment history and cirrhotic status.
Links

Article link provided by Henry E. Chang.
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.

Of Interest
Hepatitis C Treatment: What to Expect in 2017
Sift through an index of current articles covering FDA approved and investigational regimens to treat the hepatitis C virus.  

Sofosbuvir-Daclatasvir-Simeprevir Plus Ribavirin in Direct-Acting Antiviral–Experienced Patients With Hepatitis C

Clin Infect Dis (2017) 64 (11): 1615-1618.
DOI:

Sofosbuvir-Daclatasvir-Simeprevir Plus Ribavirin in Direct-Acting Antiviral–Experienced Patients With Hepatitis C
Christophe Hézode Slim Fourati Stéphane Chevaliez Giovanna Scoazec Alexandre Soulier Anne Varaut Murielle François Isaac Ruiz Françoise Roudot-Thoraval Ariane Mallat Jean-Michel Pawlotsky

Abstract

We assessed the broadly used, off-label combination of sofosbuvir, daclatasvir, simeprevir, and ribavirin in direct-acting antiviral–experienced patients, as recommended in current guidelines despite scarce data. After 24 weeks’ treatment, sustained virological response 12 weeks after the end of treatment was achieved in 6 patients (60%). Two cirrhotic patients relapsed and 2 discontinued treatment due to serious adverse events.

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Full Text Article
Article link provided by Henry E. Chang.
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.

Healio Highlights from DDW - New data on liver disease diagnosis and treatment

Digestive Disease Week
May 6, 2017 - May 9, 2017

Healio brings you the highlights from Digestive Disease Week. Refer back to this page often for the latest news from DDW, perspectives and interviews with leading researchers and clinicians, and to review archives of past meetings.

Hepatology highlights from DDW include microbiome, LT, HBV
May 26, 2017
Among the presentations at this year’s Digestive Disease Week, physician experts and clinical professionals discussed new data on liver disease diagnosis and treatment, including topics such as gut microbiota, liver transplantation, fatty liver disease and viral hepatitis, as well as advances in the world of telemedicine and unique approaches in patient management.


New Hep C Treatment Not Linked to Liver Cancer

Summary Of  Available Data:

New Hep C Treatment Not Linked to Liver Cancer
by Liz Highleyman
Contributing Writer, MedPage Today

Contrary to some earlier research, most recent studies see no association between response to DAAs and HCC

Most Researchers Find No Link
The Barcelona group stood alone among several other research groups presenting at the EASL meeting that did not see an increased risk of HCC after taking into account other factors including liver disease severity:
  • Etienne Audureau from Henri Mondor University Hospital in Paris reported that lack of SVR -- not the type of treatment -- was the strongest predictor of liver cancer in cirrhotic patients; older age, alcohol use, and impaired liver function also predicted HCC
  • Hamish Innes from Glasgow Caledonian University said that HCC risk following SVR was associated with baseline patient risk factors, but not DAA use; in a multivariate analysis, HCC risk was similar for patients treated with either DAAs or interferon
  • Dong Ji from the Hong Kong Humanity and Health Medical Center in Beijing reported no increase in HCC incidence among patients cured with DAAs compared with interferon
  • Masaaki Korenaga from Kohnodai Hospital in Japan said that SVR after treatment with sofosbuvir/ledipasvir (Harvoni) led to a reduction in HCC incidence, similar to the drop seen in patients cured with interferon
  • Vincenza Calvaruso from the University of Palermo in Sicily reported no increase in the development of new HCC among patients who achieved SVR with DAAs, compared with those cured with interferon

Recommended Links
Liver Cancer After Treatment For Hepatitis C
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. 


Push for generic drugs in India

Push for generic drugs in India
Even as India’s National Pharmaceutical Pricing Authority (NPPA) has fixed the prices of 31 more drug formulations, in yet another crackdown on prices, India's premier policy formulating agency Niti Aayog has proposed a change in the manner the government should identify drugs to be brought under price control....

While the Indian government is strongly backing generic drugs, a report from an international research team has found that the use of the generic versions of direct-acting antiviral (DAA) drugs that are available in India to treat hepatitis C virus (HCV) infection are not only cost effective, but actually save lifetime costs for treating infected patients in India....

The report states that the upfront costs of DAA are offset by the avoidance of costs incurred to treat late-stage disease....
Continue reading....

Related Articles On This Blog
HCV generics

Biologic Psoriasis Treatment Tied to Reactivation of Chronic HBV

Biologic Psoriasis Treatment Tied to Reactivation of Chronic HBV
By Reuters Staff

NEW YORK (Reuters Health) - Psoriasis patients with chronic hepatitis B virus (HBV) infection who are treated with biologic therapies are at increased risk of viral reactivation, new research shows.

But reactivation risk was minimal for patients who tested seropositive for HBV core antibody only or hepatitis C virus (HCV), Dr. Lev Pavlovsky of Rabin Medical Center Beilinson Hospital in Petach Tikva, Israel, and colleagues found.

Biologics available in Israel do not cause direct hepatic or renal toxicity, so they are an “appealing” option for patients with viral hepatitis, the researchers note in their report, online May 9 in the Journal of the American Academy of Dermatology. However, the researchers add, there have been reports of HBV reactivation in patients on biologic therapies for other illnesses.

To investigate the safety of biologics in patients testing positive for HBV or HCV, the researchers looked at clinical and laboratory data for 30 patients on biologic therapy, including four with HCV infection, 17 with past HBV infection, eight with isolated core antibody, and one patient with chronic HBV. During follow-up, which lasted an average of nearly five years, none of the patients developed hepatitis or viral reactivation.

The investigators also analyzed 49 studies found by systematic review of the literature. The studies included 312 patients followed for a mean 30.9 months. Yearly rates of viral reactivation were 0.32% in patients seropositive for core antibody, 2.42% in patients with HCV infection, and 13.92% in patients with chronic HBV infection.

One limitation of the study is that the review included heterogeneous studies of different biologic treatments, the researchers note.

“Our study indicates that low-risk patients without hepatitis who are seropositive for HBV core antibody only or HCV infection have minimal risk or no additive risk, respectively, for viral reactivation. Consequently, antiviral prophylaxis seems unnecessary,” Dr. Pavlovsky and colleagues write.

“In contrast, chronic carriers of HBV have about a 14% risk for yearly viral reactivation. These patients need to be carefully evaluated for the risk-benefit ratio of biologic therapy and receive antiviral prophylaxis,” they add.

Dr. Pavlovsky was not available for an interview by press time.

SOURCE: http://bit.ly/2qHZN9s

J Am Acad Dermatol 2017.

Thursday, May 25, 2017

Safe space for illegal drug consumption in Baltimore would save $6 million a year

Safe space for illegal drug consumption in Baltimore would save $6 million a year

Supervised facilities would also save lives, prevent infections and hospitalizations

Johns Hopkins University Bloomberg School of Public Health

A new cost-benefit analysis conducted by the Johns Hopkins Bloomberg School of Public Health and others suggests that $6 million in costs related to the opioid epidemic could be saved each year if a single "safe consumption" space for illicit drug users were opened in Baltimore.

It would also reduce overdose deaths, HIV and hepatitis C infections, overdose-related ambulance calls and hospitalizations - and bring scores of people into treatment, they found.

Carefully monitored "safe consumption" spaces, which are not legal in the United States but have been used in dozens of cities around the world, provide a clean indoor environment in which people can use their own drugs with medical personnel on hand to reverse overdoses should they occur. These facilities serve as access points to substance use disorder treatment and other vital social services for drug users, such as medical care and housing.

The authors of the study, published this month in the Harm Reduction Journal, say that the findings add economic evidence to the body of research that already links such spaces to a reduction in fatal drug overdoses and an increase in people seeking treatment. "Safe consumption" spaces are especially critical right now: Last year, the United States hit a record for the number of people who have died from drug overdose, and fentanyl, a more dangerous and powerful drug than heroin, is increasingly being added to heroin in places like Baltimore.

"No one has ever died from an overdose in a safe consumption space," says the study's senior author, Susan G. Sherman, PhD, MPH, a professor in the Department of Health, Behavior and Society at the Bloomberg School. "Thousands of lives have been saved. There are lots of doors people can walk through when they are addicted to drugs. We want them to walk through a door that may eventually lead to successful treatment - and keep them alive until they are ready for that."

Says Amos Irwin, MA, the study's lead author and program director at the Law Enforcement Action Partnership in Washington, D.C.: "Today, thousands of Baltimoreans are risking their lives to inject drugs instead of seeking treatment. We estimate that more than 100 new people would enter treatment every year if the city had a supervised injection facility. Bringing these people into a safe space actually helps reduce drug use, not increase it."

For their study, the researchers looked at the costs of operating a safe consumption space in Vancouver, the only one in North America. Then they estimated the impact on several health outcomes, based on Baltimore data.

They determined that running a 1,000-square-foot, 13-booth space in Baltimore for 18 hours a day would cost $1.8 million a year. Insite, the Vancouver facility, serves about 2,100 unique individuals a month, who perform roughly 180,000 injections per year in a space the same size.

Based on research done at Insite, they estimate that a Baltimore facility would generate $7.8 million in annual savings, preventing four HIV infections, 21 hepatitis C infections, 374 days in the hospital for skin and soft-tissue infections, six overdose deaths, 108 overdose-related ambulance calls, 78 emergency room visits and 27 overdose-related hospitalizations.

At the same time, an estimated 121 additional people would enter treatment.

"Six million dollars is a lot of money for one facility to save," Irwin says. "It is almost a third of Baltimore City's entire budget for HIV, sexually-transmitted infections and substance abuse treatment and prevention."

A bill allowing safe consumption spaces failed in the Maryland General Assembly this year. Last month, the Massachusetts Medical Society recommended opening safe consumption spaces in that state. These supervised injection facilities are a widely used public health intervention in 11 countries, mostly in Europe.

Sherman says many drug users in Baltimore are injecting on the streets or in abandoned houses, exposing them to possible violence, arrest and overdose death. Safe consumption spaces would provide clinical supervision and a clean environment, and they allow health professionals to connect drug users to critical health services. Such spaces maintain a strict prohibition on drug sharing or selling. These programs are not condoning illicit behavior, she says. They are meeting people where they are and connecting them with lifesaving resources.

The researchers did not estimate how many safe consumption spaces would be needed to service Baltimore's drug using population.

"We know what doesn't work when it comes to the so-called 'War on Drugs' in the United States because we have an opioid epidemic that is only getting worse," Sherman says. "The stakes are even higher now with so much heroin and other drugs adulterated with fentanyl. You can keep doing what you are doing or you can try something that has been proven by evidence and is considered usual care in a dozen nations."

"Mitigating the heroin crisis in Baltimore, MD, USA: a cost-benefit analysis of a hypothetical supervised injection facility" was written by Amos Irwin, Ehsan Jozaghi, Brian W. Weir, Sean T. Allen, Andrew Lindsay and Susan G. Sherman. Other collaborating institutions include the Criminal Justice Policy Foundation and the University of British Columbia.

The research was supported by grants from the National Institutes of Health's National Institute of Allergy and Infectious Diseases (P30AI094189) and the National Institute on Drug Abuse (T32DA007292) as well as Amherst College, the Criminal Justice Policy Foundation, the Law Enforcement Action Partnership and the Canadian Institutes of Health Research Postdoctoral Fellowship.

Evidence-based recommendations on the management of extrahepatic manifestations of chronic hepatitis C virus infection

In Case You Missed It

Journal of Hepatology
June 2017
Volume 66, Issue 6, Pages 1282–1299

Evidence-based recommendations on the management of extrahepatic manifestations of chronic hepatitis C virus infection
Manuel Ramos-Casals, Anna Linda Zignego, Clodoveo Ferri, Pilar Brito-Zerón, Soledad Retamozo, Milvia Casato, Peter Lamprecht, Alessandra Mangia, David Saadoun, Athanasios G. Tzioufas, Zobair M. Younossi, Patrice Cacoub on behalf of the International Study Group of Extrahepatic


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Introduction
The hepatitis C virus (HCV), a linear, single-stranded RNA virus identified in 1989, is a hepatotropic virus that causes liver cirrhosis and hepatocellular cancer and is a global health problem. It is recognized as one of the hepatic viruses most often associated with the development of extrahepatic manifestations (EHMs), which can be classified according to the principal underlying etiopathogenic process (autoimmune, inflammatory, metabolic or neoplastic) [1]. HCV infected patients with extrahepatic involvement require a multidisciplinary approach and a complex therapeutic management.

In the 1990s, various authors described the association between HCV infection with organ damage beyond the liver and a heterogeneous group of extrahepatic conditions including pulmonary fibrosis, cutaneous vasculitis, glomerulonephritis, Mooren ulcer, porphyria cutanea tarda and lichen planus, among others [[2], [3], [4]]. However, it is currently accepted that there is a weak association with some of these features [[1], [5]], and that cryoglobulinemic vasculitis (CV) is the key extrahepatic disease related to chronic HCV infection. There is growing interest in the association with both systemic and organ-specific autoimmune diseases and with the development of neoplastic haematologic processes due to the specific lymphotropism of HCV [[1], [6], [7]].

Currently, there are no international recommendations on the therapeutic management of HCV infected patients with EHMs. The first therapeutic approaches were based on immunosuppressive therapies mirroring the regimens used in non-HCV vasculitides [8]. The introduction of the first antiviral therapies combination (interferon [IFN] alpha and ribavirin [RBV]) clearly improved survival rates[9]. However, this therapeutic approach had limited virological efficacy (eradication <50% for HCV genotype 1), often required several months of therapy and had high rates of intolerance [10]. Direct-acting antiviral (DAA) therapies have recently emerged as a striking therapeutic approach for HCV infection, with a short treatment duration, minimal side effects and efficacy approaching 100% [[11], [12], [13], [14]]. These new drugs are providing the opportunity to effectively cure chronic HCV infection and reduce the burden caused by both the hepatic and extrahepatic complications of HCV, thereby offering hope for a dramatic change in patient outcomes. The objective of this international multidisciplinary consensus is to provide the first set of recommendations on a homogeneous therapeutic approach to HCV infected patients with extrahepatic involvement in the new DAA era.

Continue reading online - Full-Text

Wednesday, May 24, 2017

Indonesian buyers club helps people obtain generic hepatitis C treatment

Indonesian buyers club helps people obtain generic hepatitis C treatment

Liz Highleyman
Published: 24 May 2017
A community-led buyers club in Indonesia has helped more than 100 people get generic direct-acting antiviral (DAA) drugs to treat hepatitis C and is seeing a high cure rate, according to a presentation at the 25th International Harm Reduction Conference (HR17) last week in Montréal.

An estimated 3 million people in Indonesia are living with hepatitis C virus (HCV), according to Sindi Putri of the Indonesia AIDS Coalition (IAC). The number of people who inject drugs is estimated at nearly 106,000, of whom 77% are thought to have hepatitis C. Co-infection with HIV and HCV is common in this population.
Continue Reading

NAM aidsmap
Conference news: HR17
The 25th International Harm Reduction Conference (HR17) was held in Montréal, Canada from 14-17 May.

Related Articles On This Blog
HCV generics

Prevalence and economic burden of extrahepatic manifestations of hepatitis C virus are underestimated but can be improved with therapy

Version of Record online: 23 MAY 2017
DOI: 10.1002/hep4.1049

Prevalence and economic burden of extrahepatic manifestations of hepatitis C virus are underestimated but can be improved with therapy
Nancy Reau1,*, Francis Vekeman2, Eric Wu2, Yanjun Bao3 andYuri Sanchez Gonzalez

Links

Abstract
Despite guideline recommendations, access to hepatitis C virus (HCV) treatment is frequently restricted, with some payers approving therapy for only those with advanced disease or cirrhosis. However, delaying potentially curative treatment until the development of advanced liver disease may have costly consequences in terms of both hepatic complications and extrahepatic manifestations (EHMs) of HCV. Using a large claims database from the United States, we measured the risks and medical costs of 20 EHMs and investigated the role of treatment in different stages of liver fibrosis for mitigating the clinical and economic burden of these EHMs. After adjusting for potential confounders, including comorbid liver disease, patients with HCV had a significantly higher risk for any EHM (adjusted odds ratio, 2.23; P < 0.05) and higher EHM-related annual medical costs (adjusted medical cost difference, $6,458; P < 0.05) compared to matched patients without HCV. HCV treatment can offset the higher medical costs in patients with HCV by saving ∼$25,000 in all-cause medical costs per patient per year, with a large proportion attributable to savings in EHM-related medical costs (adjusted cost difference $12,773, P < 0.05). Finally, additional EHM-related medical costs could be saved by initiating HCV therapy in early stage fibrosis as opposed to late-stage fibrosis (adjusted medical cost difference, $10,409; P < 0.05). Conclusion: The clinical and economic burden of EHMs is substantial and can be reduced through viral eradication, especially if treatment is initiated early and not delayed until fibrosis advances. Considering that the wholesale acquisition cost of a 12-week course of therapy ranges from $55,000 to $147,000, the results of the current study suggest the cost of these treatments could be offset within 3 to 6 years by savings in all-cause medical costs. (Hepatology Communications 2017)
Continue to full text article.....

Recommended Reading
A nice collection of review articles on the extrahepatic manifestations of HCV
Published in the March 2017 issue of Journal of Advanced Research

Full Text Articles
Article link provided by Henry E. Chang.
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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.

U.S. FDA Accepts for Priority Review Bristol-Myers Squibb’s Application for Opdivo (nivolumab) in Previously Treated Hepatocellular Carcinoma

U.S. Food and Drug Administration Accepts for Priority Review Bristol-Myers Squibb’s Application for Opdivo (nivolumab) in Previously Treated Hepatocellular Carcinoma

May 24, 2017 11:15 AM Eastern Daylight Time
PRINCETON, N.J.--()--Bristol-Myers Squibb Company (NYSE:BMY) today announced that the U.S. Food and Drug Administration (FDA) accepted a supplemental Biologics License Application (sBLA) that seeks to extend the use of Opdivo (nivolumab) to patients with hepatocellular carcinoma (HCC) after prior sorafenib therapy. The FDA granted the application priority review and previously granted Opdivo orphan-drug designation for the treatment of HCC. The FDA action date is September 24, 2017.

“We believe the FDA acceptance of our application for Opdivo with priority review status is an important recognition of the significant unmet need for patients with HCC, which is often diagnosed in the advanced stage when treatment options are limited,” said Ian M. Waxman, M.D., development lead, Gastrointestinal Cancers, Bristol-Myers Squibb. “We are committed to exploring new treatment options for these patients and look forward to working with the FDA to potentially extend the use of Opdivo as a treatment option in this setting.
  
The submission was based on data from the Phase 1/2 CheckMate -040 study investigating Opdivo in advanced HCC patients with and without hepatitis B virus or hepatitis C virus infections. Data from this study were recently published in The Lancet and will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2017 during a poster discussion session on June 3, 2017 from 4:45–6:00 PM CDT in Hall D2.

Source - http://www.businesswire.com/news/home/20170524005865/en/U.S.-Food-Drug-Administration-Accepts-Priority-Review

Indian generic version of Sofosbuvir - China captures 12 smugglers

China captures 12 smugglers of Indian pharmaceuticals
Source: Xinhua| 2017-05-24 18:48:38|Editor: ying
CHANGCHUN, May 24 (Xinhua) -- Chinese police have detained 12 people for smuggling and selling Indian-made treatments for hepatitis C and cancer, authorities said Wednesday.

Customs in Changchun, the capital city of China's Jilin Province, obtained information in November 2016 that five online stores may have smuggled Indian-made medications and sold them in China at a high price, according to Xu Zhaosha of Changchun customs
Continue reading....

Of Interest
The controversy over expensive new drugs for hepatitis C
Link to research and news articles addressing the high cost of hepatitis C drugs; insurance restrictions - private insurers/Medicaid - and availability of generic versions/India, Egypt and other lower-income countries or through online "buyers clubs"

Interferon-free treatments in patients with hepatitis C genotype 1-4 infections in a real-world setting

. 2017 May 6; 8(2): 137–146.
Published online 2017 May 6. doi:  10.4292/wjgpt.v8.i2.137

Interferon-free treatments in patients with hepatitis C genotype 1-4 infections in a real-world setting
Huascar Ramos, Pedro Linares, Ester Badia, Isabel Martín, Judith Gómez, Carolina Almohalla, Francisco Jorquera, Sara Calvo, Isidro García, Pilar Conde, Begoña Álvarez, Guillermo Karpman, Sara Lorenzo, Visitación Gozalo, Mónica Vásquez, Diana Joao, Marina de Benito, Lourdes Ruiz, Felipe Jiménez, Federico Sáez-Royuela, and Asociación Castellano y Leonesa de Hepatología (ACyLHE)

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Abstract
AIM
To investigated the real-world effectiveness and safety of various regimens of interferon-free treatments in patients infected with hepatitis C virus (HCV).

METHODS
We performed an observational study to analyze different antiviral treatments administered to 462 HCV-infected patients, of which 56.7% had liver cirrhosis. HCV RNA after 4 wk of treatment and at 12 wk after treatment sustained virologic response (SVR) as well as serious adverse events (SAEs) was analyzed first for the whole cohort and then separately in patients who met or did not meet the inclusion criteria of a clinical trial (CT-met and CT-unmet, respectively).

RESULTS
The most frequently prescribed treatment was simeprevir/sofosbuvir (36.4%), followed by sofosbuvir/ledipasvir (24.9%) and ombitasvir/paritaprevir/ritonavir (r)/dasabuvir (19.9%). Ribavirin (RBV) was administered in 198 patients (42.9%). SVRs occurred in 437/462 patients (94.6%). The SVRs ranged between 93.3% and 100% for genotypes 1-4. SVRs were achieved in 96.2% patients in the CT-met group vs 91.9% patients in the CT-unmet group (P = 0.049). Undetectable HCV RNA at week 4 occurred in 72.9% of the patients. In the univariate analysis, the factors associated with SVRs were lower liver stiffness, absence of cirrhosis, higher platelet count, higher albumin levels, no RBV dose reduction, undetectable HCV RNA at week 4 and CT-met group. In the multivariate analysis, only albumin was an independent predictor of treatment failure (P = 0.04). Eleven patients (2.4%) developed SAEs; 5.2% and 0.7% of the patients in the CT-unmet and CT-met groups, respectively (P = 0.003).

CONCLUSION
A high proportion of patients with HCV infection achieved SVRs. For patients who did not meet the CT criteria, treatment regimens must be optimized.

Keywords: Hepatitis C virus infection, Genotype 1-4, Real world treatment, Direct-acting antiviral agents

Core tip: Our study analyzes the hepatitis C virus (HCV) most common genotypes treatment and all the possible combinations with direct-acting antiviral agents which are nowadays available in our country. We have found sustained virological response rates up to 90%, even in genotypes 1 and 3. The current study analyzes HCV RNA after 4 wk of treatment and 12 and 24 wk after the end of the treatment, as well as the adverse events. We analyze, separately, the patients who meet or do not meet the inclusion criteria of a clinical trial, finding that in this last group the response is lower.


DISCUSSION ONLY
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Our real-world study is representative of monoinfected, non-transplanted patients and the treatment regimens available in Spain in 2015. Because the decision to treat and the choice of treatment were entirely at the discretion of the treating physician and randomization was not possible, this study could not directly compare the effectiveness and safety of the treatment regimens.

In the general cohort, the global efficacy was high (94.6% SVR) and the results were similar to those achieved in the CTs, although almost 60% of the patients had received previous HCV antiviral treatment and more than half had liver cirrhosis.

We found that 0.4% of the subjects who achieved a SVR at week 12 subsequently relapsed at week 24 (did not achieve SVR24), and this percentage was a similar to or even lower than those found in other studies[16,17]. Therefore, this finding confirmed previous results in a real-world setting and showed good concordance between SVRs at week 12 and week 24 based on different new AAD-based regimens, including those with shorter durations and/or with drugs with lower barriers to resistance. However, in our opinion, to definitively determine a “cure” in every patient in clinical practice, a SVR must be confirmed at week 24.

Until now, few real-world setting studies have included results that consider the most frequent genotypes (1 to 4). The most significant study is the US retrospective analysis of data from 17487 patients with genotypes 1 to 4 from the Veterans Affairs (VA) National Healthcare System[18], in which a global SVR of 90.7% was found, which was lower than that in our study. This difference may be linked to early discontinuation of treatment in 4.4% of patients with available SVR data[18].

In our study, albumin was the only independent predictor of a SVR. Other studies[14,18] have also shown that albumin and other variables associated with cirrhosis or worse liver function were related to a lower SVR, thus confirming these findings in a real-world setting and with a wide number of patients and supporting the results of CTs in which patients with a more advanced liver disease have a worse response to treatment.

Most real-world studies reported results in genotype 1 HCV patients[14,19,20]. The SVR rate in our study, which included 362 genotype 1 patients, was 94.5% of the overall genotype 1 patients, which was somewhat higher than previously reported rates (SVRs over 91%), although limited differences were observed among the different DAA combinations, treatment durations and use of RBV. SMV and SOF with or without RBV was the most used treatment in our genotype 1 patients, which was likely because it was the best combination available at the beginning of the study. This treatment was used in 149 of the total genotype 1 patients. Most of these patients had liver cirrhosis and were included in the CT-unmet group because the most severe patients were prioritized. However, these patients achieved a SVR of 93.3%. In other studies with thousands of patients with genotype 1 HCV treated with this regimen, the SVR rates were lower at between 75% and 84%[14,15,21]. The main cause of the differences between our cohort and the others was likely the lower rate of subtype 1a (31.2%) and Q80K variants in our genotype 1 patients. Although these variants were not analyzed in the current study, they appeared in only 2.7% of Spanish genotype 1 patients[22].

Other treatment combinations also showed high rates of SVR in our study; i.e., 95.0% with SOF/LDV and 94.5% with OBV/PTV/r/DSV. These rates were similar to the 92.9% or 92% SVR rates derived from the first regimen presented in two US VA National Healthcare System studies[18,19] and the 94.9% or 95.1% SVR rates achieved with the second regimen in other studies in clinical practice[18,20].

In our cohort, only eleven genotype 2 patients were treated, and all of them achieved a SVR regardless of the treatment regimen used. High rates of SVR with the combination SOF + RBV were more similar to those described in Asian CTs[23] than the SVR of 79.0% or 86.2% achieved in clinical practice in the two VA studies[14,18] or the SVR of 88.2% from the recent analysis of 321 genotype 2 HCV infected HCV-TARGET participants[24]. However, the low number of genotype 2 patients in our study indicate that several of the currently recommended combinations in clinical guidelines, such as SOF and DCV[25] should be favored because they presented 100% SVR rates in all patients.

Patients with HCV genotype 3 are at a higher risk of liver disease progression and hepatocellular carcinoma development[26,27]. However, compared with other HCV genotypes, DAA combinations have lower efficacy against genotype 3 in patients with liver cirrhosis in CTs.

In the current study, the global SVR in patients with genotype 3 HCV infection was 93.3%. In our cohort, 82.2% of patients with this genotype were treated with SOF and DCV, with a global SRV rate of 90.3%-91.9% in patients with liver cirrhosis and 100% without. In others studies in real-world settings, a global SVR of 60%-70% was achieved in genotype 3 infection with SOF plus RBV[18,28]. All these studies had remarkably low rates, which was likely related to the use of combinations that are currently not recommended because of their low efficacy[25].

Patients with HCV genotype 4 infection are poorly represented in pivotal CTs of second-generation DAAs[25] and in most real-world studies. In the VA study, a SVR of 87.6% with SOF and LDV and 96.4% with OBV and PTV/r was achieved in patients with this genotype[18]. In the current study, 44 patients who were HCV genotype 4-infected were treated and the SVR rate was 95% (100% with SOF and LDV, 92.3% with OBV and PTV/r and 94.7% with SMV and SOF).

The week 4 response data were available for almost all patients in the current study. We found that 72.9% of patients had an undetectable HCV RNA at week 4, similar to another analysis[19,29]. In this last real-world setting study, significant SVR rate reductions of 7.1% to 10.5% according to the addition of RBV or not, respectively, were observed in patients who did not have an undetectable HCV RNA at week 4 compared with those with undetectable HCV RNA at week 4, which was similar to the 6% observed in the current study[19]. The clinical implications of this finding on treatment decisions, such as potentially adding RBV or extending the treatment duration based on 4 wk of on-treatment HCV RNA, warrants further study.

Despite the real-world nature of our cohort, which included a higher proportion of elderly patients and many patients with liver cirrhosis, the safety and tolerability of all regimens were good. Discontinuation rates were low (< 1%), which is similar to that of CTs, and there were no deaths during treatment or follow up. In Backus et al[20] higher early discontinuation rates of 5.3% to 15.2% according to the treatment combination were found. In contrast, of the 802 patients in the genotype 1 group from the HCV-TARGET cohort treated with SMV and SOF, the rate of discontinuation for adverse events was only 2%[15].

In patients from the genotype 1 and genotype 3 groups from the HCV-TARGET cohort, the most commonly reported AEs were fatigue and headache, which is consistent with the results presented here[15,28]. However, anemia associated with RBV was less frequent in our study.

Overall, the reported rates of SAEs (2.4%) were similar to those reported in the pivotal CTs and lower than the 5.3% or the 7.3% described in other studies in “real-world”[15,28]. Again, in the three studies, the most frequent SAEs were the same decompensating events. However, in the current study, only seven of 262 cirrhotic patients experienced decompensation.

Because the real-world population is heterogeneous, it is important to investigate the treatment outcomes in patients excluded from CTs. Thus, we divided patients into two groups: Patients who met the requirements to take part in a CT and patients who did not meet these requirements. We found that the CT-unmet patients had lower rates of SVR and higher rates of SAEs, liver decompensation and treatment interruptions than the CT-met patients. Thus, in this group of patients, it might be advisable to conduct a more rigorous follow-up investigation to closely monitor tolerability and optimize treatment regimens.

This study has the usual limitations related to its observational, real-world design and electronic data collection. Resistance testing was not performed; thus, we were unable to assess the impact of this factor. The lack of randomization limited the ability to directly compare treatment groups, which is further compounded by the small number of patients in certain subgroups.

In conclusion, our study confirmed the efficacy and safety data reported in CTs in a cohort of patients with genotypes 1-4 and a wide range of basal characteristics, including a high proportion of patients with advanced fibrosis and treatment experience. Our results confirmed and occasionally improved upon the efficacy and safety results reported in other recently published real-world setting studies with a large number of patients[8,19], and these results are in sharp contrast to the lower SVR rates reported in certain early real-world studies on interferon-free therapy with second generation DAAs[14,15]. Moreover, our results indicate that treatment regimens should be optimized in patients that do not fulfill classical CT inclusion criteria because of their lower rates of SVR and higher rates of SAEs.