Sticker Shock and the Price of New Therapies for Hepatitis C: Is it worth it?

Provided by NATAP

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"Thus, although DAA therapy may be $1000 a pill, SVR is arguably priceless......if these individuals fail to be linked to a provider willing to administer HCV therapy, or if HCV therapy is out of reach due to barriers such as cost, the potential health care burden in the long run is even higher......expensive for society.21 It is difficult, however, to justify an intervention simply by a price tag. Some treatments may be equally effective but toxicity and complexity may make one a much better value......Cost is important, but effective safe therapy is paramount."

Hepatology Feb 3 2014

Nancy S. Reau, MD, Donald M. Jensen, MD

The Center for Liver Disease
The Section of Gastroenterology, Hepatology and Nutrition
The University of Chicago Medicine

This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process which may lead to
differences between this version and the Version of Record.

The new era of antiviral therapy for hepatitis C holds great promise to finally reign in a public health nightmare, but at what expense? It has been estimated that a 12 week course of therapy could cost in excess of $84,000. Much has been written in the lay press regarding the price of these newer therapies which has led to concerns about the ability of our health care system to effectively implement and deliver these treatments to those in greatest need.1Can we justify these costs? To better understand this, it is necessary frame the discussion in the context of the economic burden of chronic liver disease against the retail cost of therapy. Product price also reflects drug development and productions expense; however this is very difficult to access.

What is success and what is it worth? According to Oxford dictionary, success is the accomplishment of an aim or purpose.2 In medicine, success can be hard to define. However, when it comes to hepatitis C therapy, sustained viral response (SVR) is a well-established surrogate for treatment success, and has been equated with a cure. Not only is SVR durable, with a less than 1% chance for late relapse, SVR has been associated with lower rates of liver cancer, cirrhosis, transplant and all-cause mortality. It leads to improved quality of life, lower risk of metabolic complications such as insulin resistance, improves glycemic control in those that are diabetic and recovers neurocognitive function. It is difficult to argue this is not success- both for the patient as well as society. How much is this worth? What is the price of prevention?

HCV is generally asymptomatic (and thus not a significant economic burden) until advanced liver disease occurs. This was confirmed by a recent study that compared the economic burden for U.S. patients with chronic hepatitis C, stratified by severity of liver disease, in a large private health insurance claims database from 2003 to 2010. The database included claims for all prescription medications and all medical services submitted for payment. Researchers examined claims from 53,796 patients with chronic hepatitis C: 41,858 (78%) without cirrhosis, 3,718 (7%) with compensated cirrhosis, and 8,220 (15%) with end-stage liver disease. Overall, the annual health care costs were estimated to be $24,176 for patients with chronic hepatitis C infection. However, when examined by disease stage, advanced disease consumed a substantially larger proportion of the total. Average annual costs were $17,277 for patients with no cirrhosis, $22,752 among patients with well-compensated cirrhosis, and $59,995 among patients with end-stage liver disease - most of which was driven by inpatient care.3 Patients with compensated cirrhosis may live for over a decade, accruing (by this model) over $270,000 in expense prior to developing end-stage liver disease. When HCV disease progresses to decompensated cirrhosis, transplant offers the best long-term prognosis, but this is not cheap. According to the United Network for Organ Sharing (UNOS)' Transplant Living Web site, the estimated U.S. average of billed charges per liver transplant in 2011 was $577,100.4, 5

Despite the risk of progression to advanced disease, most patients remain untreated. Based on two large US cohorts (Chronic Hepatitis Cohort Study: CHeCS and the National Health and Nutrition Examination Survey: NHANES) analyzed by the Division of Viral Hepatitis at the Centers for Disease Control and Prevention (CDC) only 13-18% of individuals chronically infected with HCV receive treatment.6 Other studies support this abysmal treatment uptake. In another recent interrogation of a large healthcare payer database showed that only 10.9% of 57,084 HCV infected patients have received HCV therapy.7

It is possible that many of these patients are simply waiting for better treatment options. A common quandary is when to begin therapy. Traditionally, it is felt that a cirrhotic patient has the most to gain from viral eradication, as SVR is associated with a lower risk of hepatic decompensation, liver cancer and need for transplantation.8,9 Yet, at least with 2011 triple therapy, patients with cirrhosis are more likely to experience treatment-related side effects, early termination, and are least likely to attain SVR.10 This experience is likely to improve with newer therapies. Alternatively, treating all patients with minimal fibrosis could prevent progression to advanced disease. This subset has a high probability of cure; yet, these patients are also least likely to develop HCV induced complications in the immediate future and some may never develop advanced disease. Predicting disease progression would be ideal, and baseline factors do contribute to the risk of disease progression. However, the absence of these factors cannot guarantee disease stability.

Still, it is well recognized that SVR can mitigate disease complications and, theoretically, the cost of end stage liver disease. Traditional interferon-based therapy has never been inexpensive. HCV therapy has evolved from standard interferon-alfa for 24 weeks, which offered a 6% SVR rate and would cost less than 20 thousand dollars today, to peginterferon and ribavirin (PEG/RBV) for 48 weeks, with SVR rates increasing to 40-60%11, but also with doubled the price. With the approval in 2011 of HCV protease inhibitor direct-acting antivirals (DAA), efficacy improved, but the cost increased substantially to over 70 thousand dollars. Still, this price tag is out of context. When the total cost of therapy to achieve SVR is considered, including management of complications, the price of treatment actually increases to $172,889 to $188,859 per SVR.11,12 The treatment cost per SVR may therefore be the most reasonable way to estimate the total cost impact of a new therapy. Those patients who relapse (become HCV negative but the disease recurs once treatment is discontinued) therefore cost the most - as they experience the longest duration of therapy for the least return.

The next wave of therapy (simeprevir and sofsbuvir) has again increased treatment efficacy, but the price tag is daunting. These agents shorten therapy and are much more tolerable, but are only approved in combination with PEG and RBV for genotype 1. They are expected to accumulate some additional cost driven by side effects but monitoring and management of adverse events will likely be attenuated. Sofosbuvir is also available as an all oral therapy in combination along with RBV for genotype 2 and 3, and those genotype 1 that are interferon intolerant. But the longer duration necessary for many will further increase the treatment cost.

Is this cost exorbitant?

The price of medical care in the United States has never been a bargain. According to the World Health Organization (WHO), total health care spending in the U.S. was 17.9% of its GDP in 2011, the highest in the world 14 Of each dollar spent on health care in the United States, 31% goes to hospital care, 21% goes to physician/clinical services, and only 10% to pharmaceuticals.15 Still prescription drug prices are higher in the U.S. than anywhere else in the world, and the pharmaceutical industry remains a highly profitable business.16 Manufacturing costs do not drive drug prices, as the cost of producing a drug exclusive of development) is relatively low. Companies typically price a medication based on development costs and demand, but largely demand. The logic is circular in that the escalated cost helps offset drug development and clinical trials. Investing in drug development ultimately saves money by saving lives and preventing hospitalizations.17

Although HCV treatment induces a fair amount of sticker shock, other approved medications are equally costly. HIV therapy averages 2000-5000 dollars a month, and given that it is a lifelong treatment, lifetime drug costs are more than one-half million dollars.18 Several other drugs, including treatment for multiple sclerosis and anti-neoplastic agents, “cost more than a car”. However, the majority of these high-end agents are used for niche indications such as rare enzyme defects (Gaucher Disease) or uncommon conditions such as Hunter Syndrome and paroxysmal nocturnal hemoglobinuria.19

So how can appropriate costs be determined? The cost-effectiveness of an intervention can be calculated by applying a well-being scale, where a unit of health status expresses the output of a health intervention in the number of years and the health-related “quality of life” produced by a treatment.20 Understanding both cost-effectiveness, as well as impact on the quality of life, is imperative for health policy and cost containment. Although this measure has not been performed for current HCV therapy, evaluation of other medical and surgical procedures suggest that very cost-effectiveinterventions typically include those procedures costing less than $20,000; those ranging from $20,000 to $100,000 are moderately cost-effective; and interventions costing more than $100,000 are possibly cost-effective, but expensive for society.21 It is difficult, however, to justify an intervention simply by a price tag. Some treatments may be equally effective but toxicity and complexity may make one a much better value.

Can we negotiate a better price? Although consumers have little ability to impact drug prices, drug companies do negotiate with payers and pharmacy benefit plans. Medicaid also negotiates lower prices, which is then offset by the manufacturer by increasing retail prices. Although other federal agencies can bargain with drug companies, by design Medicare is not permitted to negotiate prices.22 In addition, Medicare participants often assume some out of pocket expense. Other payers receive rebates from companies, effectively lowering the price of the medication. Rebates are not reported, but they are one factor that explains the difference between a company’s gross sales and net sales. There is no standardization for rebates, but the average size is approximately 30% of gross sales. Naturally, rebates are larger for drugs close to patent expiration or those with more significant competition.23

Most consumers are fortunate if their insurer negotiates a better price for them, and then, based on their plan, provides coverage for the medication with affordable co-pays and premiums. For consumers without insurance, or those who cannot afford their portion of the charges, assistance programs and co-pay coupon programs often exist.[(www.MySupportPath.com)]

Still, it remains unanswered if the new agents are worth their price. In some conditions, first line therapy may be a less effective agent that is escalated to a superior but more expensive therapy if it fails to control the disease. When treating viral hepatitis, this strategy is irresponsible. As described above, patients who relapse or fail a course acquire the most cost. They pay for a full course of therapy and experience all of the side effects, but fail to clear the infection. Although we have learned to use interferon and ribavirin effectively, these agents have side effects that can be life threatening. Failing therapy may also make future treatment more difficult, either through possible viral resistance or lack of approved treatment options. Cost is important, but effective safe therapy is paramount.

HCV therapy is most effective if there is adequate treatment uptake, but several barriers exist in addition to the price tag. Patients and providers do not want interferon-based therapy. Until an all-oral-option is widely available, access to physicians willing to treat HCV will be a barrier. Even if a doctor is interested in prescribing interferon, the inevitable availability of all-oral options is widely publicized and patients will be resistant to starting older stigmatized treatments. The primary consumer of HCV therapy will shift as birth cohort screening increases HCV recognition. Most baby boomers will be insured through Medicare, which is financed through U.S. Treasury trust funds, payroll taxes, income taxes and funds authorized by congress (again tax dollars) .24 HCV is also more prevalent in lower socioeconomic groups which are either uninsured or insured through Medicaid- also a tax burden. The University of Alabama recently undertook a massive screening project in their emergency room. Here HCV testing was offered to all birth cohort ER customers who were unaware of their HCV status. After the first 1287 subjects, they found a 12% prevalence of positive anti-HCV of which 72.5% were HCV RNA positive. They also found that the prevalence was much higher in those either uninsured or insured with public/Medicaid (17% for each). Those with Medicare had an 11% prevalence where as those privately insured had only a 4% prevalence. They hope to screen over 7000 individuals and identify over 800 with positive HCV antibody.25 It is easy to see how this will be a financial burden on our health care system. But if these individuals fail to be linked to a provider willing to administer HCV therapy, or if HCV therapy is out of reach due to barriers such as cost, the potential health care burden in the long run is even higher.

Thus, although DAA therapy may be $1000 a pill, SVR is arguably priceless.

Source

Gender Differences in the Quality of Life of Patients with Liver Cirrhosis Related to Hepatitis C after Liver Transplantation

Blood Purification

Vol. 36, No. 3-4, 2013
Issue release date: January 2014

Free Access

Blood Purif 2013;36:231-236
(DOI:10.1159/000356362)

Bianco T.^d · Cillo U.^b · Amodio P.^c · Zanus G.^b · Salari A.^d · Neri D.^b ·Bombonato G.^c · Schiff S.^c · Baggio G.^a · Ronco C.^{e, f} · Brocca A.^{e, f} · Soni S.^f ·Minazzato L.^d

^aStudy Center of National Health and Gender Medicine, Padua Operating Unit, ^bUnit of Hepatobiliary Surgery, ^cDepartment of Clinical and Experimental Medicine, and^dAntalgic Therapy, Institute of Anesthesiology and Reanimation, University of Padua, Padua, ^eDepartment of Nephrology, Dialysis and Transplantation, San Bortolo Hospital, and ^fInternational Renal Research Institute Vicenza (IRRIV), Vicenza, Italy

Key Words Gender differences  Hepatitis C  Liver transplantation  Pain perception Quality of life  SF-36

Abstract

Background: Hepatitis C virus (HCV) infection frequently leads to chronic liver disease, which adversely affects the quality of life (QoL) of the patient. The gender of the patient may be an important variable in the way severity of the disease is perceived. The aim of our study is to evaluate the effect of the gender variable on QoL in HCV-positive patients.Methods: This study included a total of 52 patients (26 men and 26 women) whocompleted a 1-year follow-up after liver transplantation. QoL was assessed using the SF-36 questionnaire. Results: Male subjects have significantly higher scores on physical role functioning, bodily pain and physical activity compared with females. Females have a better QoL compared to males with regard to the emotional state and mental health.Conclusions: These results show a significant effect of the gender variable on QoL in HCV patients.

© 2013 S. Karger AG, Basel

Introduction

The diagnosis of chronic liver disease has important implications on the patient's life, as it often marks the beginning of frequent medical checkups and treatment. It also involves the formalities related to enrolment into the liver transplant waiting list. In addition to the clinical effects of the liver disease, the psychological stress related to the continuous monitoring and assessments can affect health-related quality of life (HRQoL).

The World Health Organization (WHO) refers to ‘quality of life' as an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns [1]. In this sense, the HRQoL is defined as the set of physical, mental and social diseases assessed by somatic symptoms, psychological status and social interactions from the perspective of the patient, regardless of their medical condition. The international scientific community is increasingly interested in the QoL concept, particularly for the patients with chronic diseases. QoL studies can involve many different factors, ranging from the evaluation of the different effects of different diseases on daily activities and the identification of problems specific to each disease, to evaluate the effectiveness of different treatments and the specific factors that, in addition to patient compliance, determine treatment effectiveness.

In recent years, there have been numerous investigations on the QoL in patients with liver disease related to health, with particular attention to hepatitis C virus (HCV) positivity. This increased interest is justified by the significant spread of HCV in the world's population. In fact, the WHO estimated that worldwide there are about 140 million people affected by HCV, which corresponds to 2.2% of the global population. In Italy, about 2% of the general population is infected with HCV with a gradient that increases from north to south and the islands and with age (60% of patients with hepatitis) [2].

Even in the absence of overt liver disease, chronic HCV compromises HRQoL, with a negative impact on both mental health and physical well-being of the patient [3,4]. In fact, the vast majority of HCV patients present with nonspecific symptoms, such as fatigue, irritability, general malaise, abdominal pain, joint pain and headache [5]. In most cases, medical intervention is not required, however, physical and emotional health of the patient is affected. This in turn leads to inferior HRQoL for HCV patients [6]. Even if the patient is not aware of the seriousness of the disease, his psychological state is altered [7].

QoL in Patients with Liver Disease

Several studies seem to confirm a direct adverse effect of chronic HCV on HRQoL. Some recent reviews illustrate actual prospects of research in the field of QoL in patients with chronic liver disease. In a study from Britain, 72 unselected, consecutive patients with chronic HCV were compared with 30 consecutive patients with chronic hepatitis B infection and HBsAg positivity [4]. Patients with evidence of cirrhosis were excluded. SF-36 scores were markedly reduced in patients with chronic HCV infection, indicating that these patients perceived themselves as unwell and they reported a significant reduction in their QoL. Other researchers have shown that a significant percentage of HCV patients suffer from fatigue [8,9,10,11]. In one of the largest studies from France, Poynard et al. [12] reported that among 1,614 patients with HCV, 53% reported fatigue at their initial visit and the fatigue was severe in 17% of these patients. This study also found that fatigue was independently associated with female gender, age >50 years, cirrhosis, depression and purpura. In another study, HCV patients unaware of their HCV serostatus scored significantly worse in 3 parameters of general health, vitality and mental health [13]. Those aware of their serostatus did not differ demographically, clinically, virologically or serologically from those who were unaware, nor was there a link between QoL scores and objective measures of ill health. Numerous observations suggest that HCV may exert a direct effect on HRQoL through unknown mechanisms [14,15,16]. One possibility is that HCV may act within the central nervous system, since replicating viruses have been found within the nervous system tissue. Moreover, neuropsychiatric symptoms like fatigue, malaise, depression and cognitive impairment are among the most common complaints of patients with chronic hepatitis C and occur independently of liver disease or treatment status.

Importance of the Gender Variable

Over the past 30 years, medicine has reached incredible goals, including the description of the human genome, the ability to intervene at the beginning and end of life, the application of newest technologies for betterment of the patients, to name only a few. The achievements in many fields of medicine are based on evidence connected with guidelines. However, female gender has been inadequately represented in many of the epidemiological studies, which limits meaningful statistical analysis in many disorders.

The ‘woman question' emerged in 1991 when Bernadine Healy, the first female director of the National Institute of American Public Health, wrote a famous editorial in the New England Journal of Medicine [17]. She coined the term ‘Yentl syndrome' to highlight the gender-based disparities in the treatment and outcome of coronary artery disease in the intensive care unit (Yentl was a heroine of a Jewish story where a girl shaved her hair and disguised herself as a boy to enter religious training). Women in the intensive care unit were subjected to less diagnostic and therapeutic procedures than men and fewer invasive procedures such as cardiac catheterization and coronary artery bypass surgery [18,19]. Moreover, large prevention trials in patients with myocardial infarction did not include women at all. A clear discrimination by the cardiologists against the female patient was aptly emphasized. This editorial stirred basic researchers and clinicians around the world and was followed by a series of publications and studies designed to examine gender differences in various aspects of cardiovascular disease.

Another cornerstone of gender medicine was the Fourth World Conference on Women held in Peking in 1995, where the conviction to apply the principle of gender equality in all activities, including those for health, was considered a basic human right.

In 2002, the WHO established the Department for Gender and Women's Health to recognize the differences in disease burden and treatment between men and women. In 1999, the Italian Ministry for Equal Opportunities formally established a new group with the aim of working on gender disparities in medicine through a project entitled ‘A measure of health to a woman'. In 2001, a report on women's health was presented to the parliament and in 2003 a ‘Guide to women's health' was published. In Italy, the attention to the gender variable is now supported by the National Center for Health and Gender Medicine. The Center aims to gather information, impart training and encourage research in all fields of medicine. It also aims to network all Italian centers interested in these issues.

With regard to QoL in patients with chronic liver disease, the gender variable is not systematically studied so far. The aim of the present study is to assess the effect of the gender variable on the subjective evaluation of QoL in patients with chronic HCV infection.

Patients and Methods

SF-36 Questionnaire

SF-36 is the best-known, patient-oriented questionnaire for the assessment of one's general health condition. This test is the short form of the Medical Outcome Study questionnaire, which was developed by John Ware (the principal investigator) and his colleagues in the 1980s and was subject to successive modifications by researchers from various medical specialties [20]. The SF-36 is a generic instrument that proposes to evaluate the QoL from the patient's point of view. It is made up of 36 items divided into 8 scales (table 1) whose purpose is to evaluate the various aspects related to the patient's health and thereby furnish a global assessment of the patient's mental and physical well-being. To each question, a rough score is assigned; this initial score is further elaborated to furnish a final ranking only after evaluation of all answers given. The final response is given and the relationship between specific answers is evaluated to determine the score on each scale. Scoring on each scale is from 1 to 100, with higher values being indicative of a better-perceived QoL relative to one's health status (fig. 1). Scoring and standard deviations will vary from scale to scale and are also dependent on age. Its validity is recognized by the international community.

Patients

This study included a total of 52 patients (26 men and 26 women) who completed a 1-year follow-up after liver transplantation. The HRQoL was assessed using the SF-36 questionnaire. The scores in the various domains of the questionnaire were compared using Student's t test. Analyses were performed using the statistical software SPSS 11.0.

Results

Male subjects have significantly higher scores on physical role functioning (daily activities or work is less impaired by physical health than in females), bodily pain (minor limitations due to pain) and physical activity (fewer constraints on the execution of physical activity in general) compared with females. On the other hand, females have a better QoL compared to males with regard to emotional role functioning (less impaired at emotional level) and mental health (self-satisfied and better mood stability).

Discussion

The way to deal with a disease and recovery will vary from person to person but there are gender differences that are often overlooked or incorrectly addressed. The significant difference between males and females with respect to ‘bodily pain' may be explained by the effects of various hormones on the body. Current research shows that estrogen would increase nervous system activity; this effect manifests itself in the increased transmission of pain stimuli and pain sensitivity of women. Conversely, testosterone has an analgesic effect and can reduce pain sensitivity in men [21]. Many previous studies dealing with behavioral responses evoked by nociceptive stimuli have demonstrated an increased sensitivity of females [22].

In our study, male patients scored higher in the category of ‘physical functioning' and ‘physical role functioning', which are the parameters related to physical activity and perceived limitations. The female patients scored less in both parameters, suggesting impaired QoL. This may partly be explained by the effect of ‘fatigue' in the posttransplant period. In an elegant cross-sectional study, van den Berg-Emons et al. [23] investigated the incidence, etiology, severity and factors of influence of fatigue in liver transplant recipients and concluded that the female gender perceives fatigue with greater severity.

In addition, sociocultural factors have to be considered. In fact, recent studies highlight the issue of gender difference in pain perception. It has been observed that for the same objective disease women report more pain than men [24]. These observations emphasize the fact that QoL assessment in liver transplant patients should not only include the clinical and biological condition of the patient but also psychosocial and cultural aspects. In this regard, it is also interesting to note that although female patients score less in the parameters ‘physical functioning' and ‘physical role functioning', they score better in the parameters of ‘emotional role functioning' and ‘mental health'. This highlights a better ability of females to manage stress and psychoemotional demands in the posttransplant setting. This could indicate differences in the ability of coping with stress between males and females of the study population.

Studies in the experience of pain in patriarchal ideology have highlighted ‘the central role of etiologic and coping strategies (‘being a good mother' to the female gender), suggesting that the patient needs pain to give meaning to their symptoms. It also helps to avoid negative feelings of despair and isolation. In this study, both males and females reported the common belief that a woman is better able to cope with painful events. This belief is also supported by the importance of the maternal role in women (experience of childbirth, breastfeeding, primary involvement in child rearing and emotional aspects of children) and explanations relating to the increased use of emotional expressiveness and the likelihood of seeking help and support of females. Recent studies have demonstrated sex differences in response to painful situations in teenagers and adolescents. It has been observed that males would mostly use distracting behavior while females make greater use of social support and positive self statements [25].

Studies on coping styles in the course of chronic diseases have shown that being active, thinking positively and expressing emotions positively correlated with significantly higher levels of functioning, with more positive scores in the clinical measures of disease and higher levels of psychological adjustment. The ability to adequately manage the transplant event and its consequences may foster greater satisfaction and improve QoL and HRQoL. In this sense, the gender differences in the QoL questionnaire identified in this study can help to direct attention to the most problematic and often neglected aspect for a patient undergoing a liver transplant by directing care and interventions in the posttransplant period in relation to an important variable such as gender.

Conclusion

HCV confers an inferior QoL to the patients. This effect is perceived by males and females in different ways.

References

Source

Hepatitis C: How might the new AASLD/IDSA recommendation impact the category?

Provided by Zitter Health

Lee Goldberg, Director, Syndicated Research, Zitter Health Insights

FEBRUARY 5, 2014

The HCV category is certainly dynamic enough, with numerous agents poised for approval in the next 18 to 24 months. Still, the release last Wednesday of the AASLD/IDSA Recommendations for Testing, Managing, and Treating Hepatitis Cadded another variable for payers and manufacturers to consider before determining their strategies. The recommendations were both confirmatory and surprising and it remains to be seen how payers will ultimately integrate them into management.

The Recommendations fully endorse new oral agents as the standard of care, advocating sofosbuvir first among treatment-naïve, genotype 1 patients who are eligible for interferon, followed by a simeprevir-based regimen as an alternative. The panel made a comparable recommendation for genotype 4 patients, then endorsed sofosbuvir for treatment of patients with genotypes 2 and 3, per label. Endorsements for telaprevir and boceprevir-based regimens were withdrawn as being “markedly inferior to the preferred and alternative regimens.”

However, not all endorsements followed the obvious path, namely those for patients intolerant to interferon. Labeling for sofosbuvir permits usage “in combination with ribavirin for 24 weeks . . . for CHC patients with genotype 1 infection who are interferon ineligible.” Nonetheless, the AASLD/IDSA made its primary treatment an off-label regimen of sofosbuvir plus simeprevir in combination for treatment-naïve, interferon-ineligible genotype 1 patients. It’s a safe assumption the panelists were impressed with the 90%-plus SVR rates achieved in the ongoing phase 2 COSMOS study, but it’s less clear payers will hold the same opinion.

Early research from the Hepatitis C Impact Monitor, a multi-stakeholder view of this rapidly changing area, published by Zitter Health Insights, indicates a majority of payers (52%) hold the guidelines as meaningfully or significantly influential on their determination of utilization management of the HCV category.  By itself that finding would indicate positive coverage of the sofosbuvir/simeprevir pairing.  But an even larger majority of the same payer sample, this time 80%, indicated they’re more unlikely than likely to cover those drugs in combination.  But that was before the guidelines were released.

To begin developing an understanding of how payers and doctors expect to change their behavior as events occur, we asked four pharmacy directors from national payers (in aggregate representing approximately 25 million commercial lives) how they anticipate their organizations will react.  While it’s still early for many to have determined final policies, reactions were evenly split.  One participant commented, “We try to support evidence based guidelines, but, the evidence is not there to support use at phase 2.  We’ll need more evidence development.” However, another pharmacy director was more resigned, commenting, “We won’t have a choice.  There’s no way to combat the recommendation.”
Combat may be a strong word, but may not be far from an accurate description because physicians appear on board. Prior to publication nearly a majority (47%) of specialists were more likely than unlikely to prescribe the combination. We expect those figures to increase because seventy-three percent of them grant the guidelines meaningful or significant influence in their prescribing decisions.

Perhaps beneficially for pharmacy directors, the conundrum about off-label sofosbuvir/simeprevir coverage comes with an expiration date. The AASLD/IDSA includes the caveat that “This regimen should be considered only in those patients who require immediate treatment, because it is anticipated that safer and more effective IFN-free regimens will be available by 2015.”  Which means payers will have new guidelines to digest upon the approval of Gilead’s sofosbuvir/ledipasvir, or of AbbVie’s triple therapy, or of Boehringer’s faldaprevir/deleobuvir. In the interim, payers will weigh the nature of Phase 2 results against the imprimatur of the AASLD.  Each of the four pharmacy directors we spoke with on Monday indicated their organization is currently reviewing the Recommendations document but hadn’t yet made a final policy determination.  Zitter’s Hepatitis C Impact Monitor will continue to examine the changing HCV landscape, providing timely, deep insights into non-clinical factors that influence agent access and adoption.

Source

Hepatitis C treatment shifts as new drugs emerge

Kim Painter, Special for USA TODAY 6:29 p.m. EST January 29, 2014

Treatment for liver-damaging virus is changing fast. Experts release new guidelines.

Sofosbuvir, with the brand name Sovaldi, is among new medications changing the treatment of hepatitis C.(Photo: Gilead Sciences Inc.)

John Billeris has tried and failed four grueling rounds of treatment for his chronic hepatitis C infection over the past 15 years. He is not convinced that his fifth try — with what he jokingly calls "magic medicine" — will be the charm. But he says the three-drug regimen he started on Christmas is definitely easier to take.

"I saw the doctor a couple of weeks ago… and I told him this (stuff) is not working because I don't feel anything," says the 59-year-old semi-retired real estate agent from Oyster Bay, N.Y. Since then, Billeris says, he's developed a familiar "anemic feeling," but still nothing like the persistent flu-like symptoms he has endured in the past.

That's because Billeris' new treatment does not include one drug that, until now, has been essential for patients like him: interferon, a medication known for causing fevers, headaches, fatigue, mood swings and other unpleasant and sometimes dangerous side effects. It does include two drugs approved by the Food and Drug Administration in late 2013, sofosbuvir from Gilead Sciences, Inc., and simeprevir from Janssen Therapeutics.

Those medications, and others the FDA is expected to consider soon, are part of what experts are calling a revolution in treatment for 3 million people in the USA chronically infected with hepatitis C, the nation's leading cause of liver cancer and liver transplants.

Changes in treatment are coming so fast that several medical groups on Wednesday took an unusual step: posting preliminary online treatment guidelines that will evolve as more medications become available.

Those medications could soon eliminate the need for interferon injections for most patients. They also are expected to make treatment faster, easier and more effective than older regimens, which last at least six months and succeed about 75% of the time, experts say.

"The ideal would be a single pill once a day, for eight or 12 weeks, with success rates of greater than 90%," says Donald Jensen, a liver disease specialist from the University of Chicago and co-chair of the committee behind the guidelines posted at HCVguidelines.org by the American Association for the Study of Liver Diseases, the Infectious Diseases Society of America and the International Antiviral Society-USA.

While single-pill therapies are not yet available and the FDA has not yet approved an interferon-free regimen for the majority of patients, the experts say doctors can combine drugs on the market to get faster, easier, more effective treatment for many patients who need care now. In some cases, that will mean using combinations not explicitly approved by the FDA — including the interferon-free cocktail Billeris is using. The guidelines say it is an option for hepatitis C patients with genotype 1 (the most common strain) who can't tolerate interferon or have certain conditions, including depression.

The guidelines don't carry the same weight as those that go through formal reviews to be published in medical journals, "but we are saying that if these were our patients, this is how we would handle them," says committee co-chair David Thomas, a liver specialist at Johns Hopkins School of Medicine, Baltimore.

The guidelines will be "enormously valuable" in convincing more insurers to cover the very expensive emerging treatments, says Douglas Dieterich, a liver specialist at Mount Sinai Hospital, New York. He says some have been refusing to pay for the combination of sofosbuvir, which costs $84,000 for 12 weeks, and simeprevir, which costs $66,000 for 12 weeks, according to manufacturers.

The prices for the new drugs, especially, sofosbuvir, at $1,000 a pill, also have drawn criticism from patient advocates who say high prices will limit access in the USA and worldwide.

"Gilead is exploiting the fact that this is essentially a cure for a deadly disease," says Michael Weinstein, president of the AIDS Healthcare Foundation.

Gilead believes the price of sofosbuvir "is fair, based on the value it represents" to patients, company president John Milligan said in a statement. Most private insurers are covering the drug in FDA-approved combinations, he says, and the company is working with Medicaid and Medicare to set terms for access under those plans. The company also has an assistance plan for uninsured patients and those who need help with co-pays.

The new expert guidelines "are not designed to address cost," Jensen says. "Our recommendations are based on what we think is best for patients."

The new guidelines also do not say which patients doctors should treat now and which patients can wait — a crucial issue since hepatitis C can cause varying degrees of harm and take decades to cause symptoms. A future version will address that issue, Thomas says.

Many people don't even know they have the infection. But the federal Centers for Disease Control and Prevention says it is so common among Baby Boomers that everyone born between 1945 and 1965 should be tested. The virus spreads through shared needles, birth and, sometimes, sex. About 5% of people with chronic infections eventually die of cancer or cirrhosis, the CDC says.

Getting tested is especially crucial now, Thomas says. "All the major advances in treatment are insignificant if a person doesn't even know they have the infection."

Of course, those advances in treatment still need to pass the test of real-world use — a test that some previous medical advances have failed. Billeris, for one, says, "I'm not optimistic — but I am hopeful."

Source

Some receive unnecessary prioritization for liver transplantation, says Penn Medicine study

PUBLIC RELEASE DATE: 5-Feb-2014

Contact: Lee-Ann Landis Donegan
leeann.donegan@uphs.upenn.edu
215-349-5660
University of Pennsylvania School of Medicine

Findings could influence process for allocation of scarce organ resources

(PHILADELPHIA) – Patients waiting for liver transplants who develop hepatopulmonary syndrome (HPS), a lung disorder associated with end-stage liver disease, are eligible to move up on the wait list. In a new paper published in Gastroenterology, however, Penn Medicine researchers argue the so-called "exception points" given to these patients award some HPS patients unnecessary priority over others on the list, which includes about 17,000 patients.

The current U.S. transplant allocation system prioritizes patients based on medical urgency using the Model for End Stage Liver Disease (MELD) score, which takes into account the expected three-month survival due to end-stage liver disease, but does not consider other, unrelated medical complications. As a result, a system that allows wait-list candidates with certain conditions, HPS among them, to be eligible for exception points to increase their waitlist priority has been developed.

"To examine the impact of HPS MELD exception points on outcomes, we examined the relationship between patients' blood oxygen levels and outcomes in a national cohort of patients who received HPS exception points, and compared survival in HPS vs. non-HPS patients," says David Goldberg, MD, MSCE, instructor of Medicine at the Perelman School of Medicine of the University of Pennsylvania and lead author on the study.

HPS is found in approximately 20 percent of patients awaiting liver transplant and is associated with a worse health-related quality of life. The condition is known to double the risk of death among patients evaluated for liver transplantation.

The Penn researchers looked at data from February 2002, the date the exception point program commenced, to December 2012. During this time, 973 patients on the liver transplant list received HPS exception points. While post-transplant survival was similar in HPS vs. non-HPS patients, post-transplant survival in HPS patients varied based on the severity of pre-transplant oxygen saturation levels.

The team found that patients with the poorest oxygen saturation levels (lower than 44 mm Hg) had a significantly lower three-year post-transplant patient survival rate.

Comparatively, significantly more non-HPS waitlisted patients, who did not receive exception points, died on the waitlist or within 90 days of waitlist removal, while a great proportion of HPS waitlist candidates were transplanted (73 percent vs. 43 percent). In addition, the study showed that only 49 percent of HPS transplant recipients had clear evidence of clinical indications for transplantation aside from HPS, as compared with 89 percent of non-HPS transplant recipients.

The findings refute recent reports and demonstrate an association between pre-transplant oxygen levels and post-transplant mortality, suggesting that the criteria for doling out exception points be adjusted based on patients' oxygenation, and suggesting an over-prioritization of all HPS patients in the current system.

This study represents the largest analysis of liver transplant waitlist candidates with HPS to date.

"These data, we hope, can provide some guidance to UNOS, as the exception point policy comes under revision," says Goldberg. "As organs are a scarce resource, we want to make it easier for the patients in the most urgent need to be prioritized as such, according to evidence-based criteria."

###

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 16 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $398 million awarded in the 2012 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2012, Penn Medicine provided $827 million to benefit our community.

Source

Can-Fite Submitted Phase II Study Protocol with CF102 to Treat Patients with Advanced Liver Cancer

PRESS RELEASE February 6, 2014, 7:06 a.m. ET

CF102 has Orphan Drug Designation from U.S. FDA

Global Liver Cancer Drug Market is Expected to Exceed $2 Billion by 2015

PETACH TIKVA, Israel, Feb. 6, 2014 /PRNewswire/ -- Can-Fite BioPharma (TASE: CFBI), (OTC: CANFY), a biotechnology company with a pipeline of proprietary small molecule drugs that address inflammatory and cancer diseases, announced today that a Phase II study protocol for the treatment of advanced liver cancer with its CF102 drug candidate has been submitted.

The company plans to conduct the Phase II study in Israel, Europe and the US and will include 78 subjects (less than what has been reported previously since the company is treating a patient population with a more advanced disease) with second-line treatment of advanced hepatocellular carcinoma with Child-Pugh Class B cirrhosis. The study will investigate the efficacy and safety of CF102 vs. placebo. The protocol has been submitted to the ethics committee in Israel and the company intends to follow up with European and US submissions shortly. The study protocol was developed with the assistance of Dr. Keith Stuart, MD, Chairman, Department of Hematology and Oncology Professor of Medicine, Tufts University School of Medicine a well-known internationally expert in Liver Cancer.

The US Food and Drug Administration (FDA) has granted Orphan Drug designation for CF102, for the treatment of hepatocellular carcinoma.

According to Global Industry Analysts, the global liver cancer drug market is expected to exceed $2 billion by 2015.

The company reported earlier that data from the Phase I/II study was published recently in The Oncologist, one of the leading journals in this field, and was presented at the 18th World Congress on Advances in Oncology. The company reported that the Phase 1/II study data demonstrated that the trial objectives were successfully achieved, demonstrating a very favorable safety profile for CF102 in a patient population with hepatocellular carcinoma and Child-Pugh cirrhosis classes A and B. In addition, the median overall survival time was very encouraging given that most patients were treated in the second-line setting and some were Child-Pugh Class B. Another finding indicated that the A3 adenosine receptor, which is the target of CF102, can serve as a biomarker to predict the patients' reaction to treatment with CF102. Interestingly, one of the patients included in the Phase 1/II study has been treated for 4 years with CF102 and is continuing to be treated, with CF102.

About CF102

CF102 is a small orally bioavailable drug which binds with high affinity and selectivity to the A3 adenosine receptor. The latter is highly expressed in tumor cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug. In our pre-clinical and clinical studies, CF102 induces a robust anti-tumor effect via de-regulation of the Wnt signaling pathway, resulting in apoptosis of liver cancer cells.

About Can-Fite BioPharma Ltd.

Can-Fite BioPharma Ltd is an Israeli public company, the ordinary shares of which are traded on the Tel Aviv Stock Exchange (the "TASE") (TASE: CFBI). Level II American Depository Receipts of the Company currently trade on the NYSE MKT (NYSE MKT: CANF). Can-Fite, which commenced business activity in 2000, was founded by Pnina Fishman, Ph.D., researcher in the Rabin Medical Center, and Ilan Cohn Ph.D., patent attorney and senior partner at Reinhold Cohn Patent Attorneys in Israel. Dr. Fishman serves as the Chief Executive Officer of Can-Fite. Dr. Fishman founded Can-Fite on the basis of her scientific findings, and Can-Fite is focused on the development of small molecule orally bioavailable drugs, in particular, ligands that bind to the A3 adenosine receptor. Such drugs mediate anti-inflammatory and anti-cancer effects and the A3AR is developed as a biological predictive marker. Can-Fite's lead drug candidate, CF101, is in clinical development for the treatment of autoimmune inflammatory diseases including Rheumatoid Arthritis and Psoriasis. Can-Fite's CF102 drug candidate is being developed for the treatment of liver diseases and CF602 is being developed for the treatment of inflammation and sexual dysfunction. To date, more than 1000 patients have participated in clinical trials conducted by Can-Fite. Can-Fite previously spun off it's activity in the ophthalmic field to OphthaliX Inc., in which it holds 82%, and is currently listed on the U.S. Over-the-Counter Markets (OTCQB: OPLI).

Contact:

IRTH Communications, LLC

Robert Haag

canfy@irthcommunications.com

Forward-Looking Statements

This press release contains forward-looking statements, about Can-Fite's expectations, beliefs or intentions regarding, among other things, its product development efforts, business, financial condition, results of operations, strategies or prospects. In addition, from time to time, Can-Fite or its representatives have made or may make forward-looking statements, orally or in writing. Forward-looking statements can be identified by the use of forward-looking words such as "believe," "expect," "intend," "plan," "may," "should" or "anticipate" or their negatives or other variations of these words or other comparable words or by the fact that these statements do not relate strictly to historical or current matters. These forward-looking statements may be included in, but are not limited to, various filings made by Can-Fite with the U.S. Securities and Exchange Commission (the "SEC"), press releases or oral statements made by or with the approval of one of Can-Fite's authorized executive officers. Forward-looking statements relate to anticipated or expected events, activities, trends or results as of the date they are made. Because forward-looking statements relate to matters that have not yet occurred, these statements are inherently subject to risks and uncertainties that could cause Can-Fite's actual results to differ materially from any future results expressed or implied by the forward-looking statements. Many factors could cause Can-Fite's actual activities or results to differ materially from the activities and results anticipated in such forward-looking statements, including, but not limited to, the factors summarized in Can-Fite's filings with the SEC and in its periodic filings with the TASE. In addition, Can-Fite operates in an industry sector where securities values are highly volatile and may be influenced by economic and other factors beyond its control. Can-Fite does not undertake any obligation to publicly update these forward-looking statements, whether as a result of new information, future events or otherwise.

SOURCE Can-Fite BioPharma

/Web site: http://www.canfite.com/

Source

Gilead to license hepatitis C drug to lower-cost manufacturers in India

Thu Feb 6, 2014 4:28am IST

(Reuters) - Gilead Sciences plans to license its breakthrough hepatitis C drug Sovaldi to a number of Indian generic pharmaceutical manufacturers, allowing for lower-priced sales of the medication in that developing nation, according to the company.

Although prices for the drug have not been set, company spokesman Nick Francis said in an emailed statement on Wednesday that Gilead aims to establish "tiered pricing."

For example, the price discussed for 24 weeks of Sovaldi therapy would run about $2,500 for certain patients at public hospitals, community clinics and non-governmental agencies in India, the Hindu Business Line reported earlier this week.

"Providing treatment in resource-limited settings presents complex challenges, and we will work with partners in multiple sectors around the world to ensure our access program reaches as many patients as possible," Francis said.

Gilead said final details of the program in India will be announced in coming months. The company has a similar program in place for lower-cost versions of its HIV/AIDS drugs.

In the United States, where Sovaldi was approved by regulators in December, the drug costs $84,000 for 12 weeks of therapy or $1,000 for a daily pill.

The Foster City, California-based company has said the price is fair because the treatment offers a potential cure for the liver-destroying virus without injections of interferon, which can cause severe side effects that compromise patient outcomes.

Prices in Europe are also lower than in the United States. The cost for treatment in the United Kingdom is about $57,000 while the price in Germany is around $66,000, the company has said.

Analysts have estimated that the drug will eventually generate billions of dollars in annual sales. Sanford Bernstein has forecast sales this year alone of $6.7 billion.

But some have questioned whether that is achievable. Many patients including those in the United States, where more than half of hepatitis C patients are estimated to rely on public funding, could have difficulty securing reimbursement for such a high-priced drug.

Other companies including Johnson & Johnson, AbbVie and Merck & Co are also working to develop new hepatitis C treatments with some in advanced stages of clinical studies.

Gilead, which reported 2013 earnings on Tuesday, declined to include an estimate for hepatitis C sales in its 2014 sales forecast, saying only that Sovaldi sales so far have been strong and broadly based.

Sales of Sovaldi in the last three weeks of 2013 totaled more than $139 million.

The World Health Organization estimates that about three percent of the world's population has been infected with the hepatitis C virus and that more than 170 million chronic carriers are at risk of developing liver cirrhosis, liver cancer or both.

Shares of Gilead fell $3.87, or nearly five percent, to close at $78.15 in Nasdaq trading on Wednesday. Over the past two years, the stock has nearly tripled.

(Reporting By Deena Beasley; Editing by Diane Craft)

Source

Patient-important benefits of clearing the hepatitis C virus through treatment: a simulation model

Journal of Hepatology

Article in Press

Hamish Innes, David Goldberg, Geoffrey Dusheiko, Peter Hayes, Peter R. Mills, John F. Dillon, Esther Aspinall, Stephen T. Barclay,Sharon J. Hutchinson

Received 7 August 2013; received in revised form 20 January 2014; accepted 27 January 2014. published online 06 February 2014.
Accepted Manuscript

Abstract

Background & Aims

Given an appreciable risk of adverse-effects, current therapies for chronic hepatitis C virus (HCV) infection pose a dilemma to patients. We explored, via simulation modelling, patient-important benefits of attaining a Sustained Viral Response (SVR).

Methods

We created the HCV Individualised Treatment-decision model (the HIT-model) to simulate, on a per patient basis, the lifetime course of HCV-related liver disease according to two distinct scenarios: (i) SVR attained, and (ii) SVR not attained. Then, for each model subject, the course of liver disease under these alternative scenarios was compared. The benefit of SVR was considered in terms of two patient-important outcomes: (1) The percent-probability that SVR confers additional life-years; and (2) The percent-probability that SVR confers additional healthy life-years, where “healthy” refers to years spent in compensated disease states (i.e. the avoidance of liver failure).

Results

The benefit of SVR varied strikingly. It was lowest for patients aged 60 years with initially mild fibrosis; 1.6% (95% CI: 0.8-2.7) and 2.9% (95% CI: 1.5-4.7) probability of gaining life-years and healthy life-years, respectively. Whereas it was highest for patients with initially compensated cirrhosis aged 30 years; 57.9% (95%CI: 46.0-69.0) and 67.1% (95%CI: 54.1-78.2) probability of gaining life-years and healthy life-years, respectively.

Conclusions

For older patients with less advanced liver fibrosis, SVR is less likely to confer benefit when measured in terms of averting liver failure and premature death. These data have important implications. Foremost, it may inform the contemporary patient dilemma of immediate treatment with existing therapies (that have poor adverse effect profiles) versus awaiting future regimens that promise better tolerability.

Abbreviations: HCV, Hepatitis C Virus, SVR, Sustained Viral Response, HIT model, Hepatitis-C Individual-based Treatment-decision model,HCC, Hepatocellular Carcinoma, NSS, Number need to attain SVR, NNT, Number needed to treat, SA, Sensitivity Analysis

Keywords: Hepatitis C, Chronic Hepatitis C, Patient-centred, Patient-important outcomes, Markov model, Simulation model, Antiviral treatment,Adverse effects, Risk-benefit ratio

Source

The Relationship of Hepatitis C Virus Infection with Diabetes in the United States Population

Hepatology

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Original

Constance E. Ruhl M.D., Ph.D.^1,*, Andy Menke Ph.D.¹, Catherine C. Cowie Ph.D.²,  James E. Everhart M.D., M.P.H.²

DOI: 10.1002/hep.27047

Copyright © 2014 American Association for the Study of Liver Diseases

Publication History
Accepted manuscript online: 5 FEB 2014 10:25AM EST
Manuscript Accepted: 31 JAN 2014
Manuscript Revised: 5 DEC 2013
Manuscript Received: 20 SEP 2013

Keywords: insulin resistance; alanine aminotransferase;  gamma glutamyltransferase;  National Health and Nutrition Examination Survey;  epidemiology

ABSTRACT

An association of hepatitis C virus (HCV) infection with diabetes has been reported in many studies, but few have been population-based and applied standard criteria for diabetes diagnosis. We examined this relationship using recent population-based data from the U.S. National Health and Nutrition Examination Survey. 15,128 adult participants in the 1999-2010 surveys had data on diabetes status and serum HCV antibody (anti-HCV) or HCV RNA. Using American Diabetes Association criteria, diabetes was defined as a health care provider diagnosis, serum hemoglobin A_1C (A1C) ≥6.5%, or fasting plasma glucose (FPG) ≥126 mg/dL; pre-diabetes as A1C 5.7%-<6.5% or FPG 100-<126 mg/dL; and normal glucose as A1C <5.7% and FPG <100 mg/dL. Odds ratios (OR) for diabetes and pre-diabetes, comparing persons with HCV infection to those without, were adjusted for demographics, BMI, C-reactive protein, smoking, drinking, and blood transfusion before 1992. Among participants without diabetes, we compared mean insulin resistance, estimated using homeostasis model assessment (HOMA-IR), by HCV status. The overall prevalence of anti-HCV+ was 1.7%, of HCV RNA+, 1.1%, of diabetes, 10.5%, and of pre-diabetes, 32.8%. The prevalence of diabetes and pre-diabetes did not differ by HCV status. In multivariate-adjusted analysis, diabetes remained unassociated with anti-HCV (OR=1.0, 95% confidence interval (CI), 0.6-1.7) or with HCV RNA (OR=1.1, 95% CI, 0.6-1.9). In contrast, elevated alanine aminotransferase and gamma glutamyltransferase activities were associated with diabetes regardless of HCV status. HOMA-IR was not associated with HCV markers in unadjusted or multivariate-adjusted analyses (p>0.05). Conclusion. In the U.S. population, HCV was not associated with diabetes, or with insulin resistance among persons with normal glucose. Previously reported relationships of HCV with diabetes were possibly attributable to the effect of elevated liver enzymes. (Hepatology 2014;)

Source

Injection behaviors among injection drug users in treatment: The role of hepatitis C awareness - Does HCV+ Awareness Among IDUs Reduce Needle Sharing

Provided by NATAP

Download the PDF here

Does HCV+ Awareness Among IDUs Reduce Needle Sharing? This study found NO - ."In adjusted analysis (Table 2), recent syringe/needle sharing was more likely among those who reported they were HCV-positive compared with those who were HCV negative/unaware (aOR 2.37 [95% CI 1.15, 4.88]), and among IDUs obtaining needles from the street, using any opioids, marijuana, or injected crack cocaine; sharing was less likely among males and participants with some college education......More HCV-positive IDUs reported recent syringe/needle sharing compared with those with HCV negative/unknown status (44.6% vs. 38.5%, p = .131), though this was not statistically significant"

from Jules: with the advent & revolution of new HCV oral & interferon-free therapy it will be important to provide education to at-risk patients about the risks for-re-infection with HCV. It is important to provide treatment to IDUs as persons but also for society. All too often now treatment for IDUs is withheld for a number of reasons including because IDUs are at risk for continuing risky behavior, sharing unclean needles & getting re-infected. Instead treatment for IDUs should be viewed as important for the patient, for prevention, ad for society & treatment should be viewed as an opportunity to provide education about preventing re-infection, why & how the patient should not be re-infected. Often this means addressing the patient's risky behavior, which could be sharing used/unclean syringes for the IDU or continued risky sexual & drug behavior for MSM. In recent studies in NYC & in London re-infection was cited among MSM due to continued unsafe drug & sex behavior, in fact re-infection was reported to occur 2-3 times after successful treatment for some individuals. In recent studies re-infection among IDUs has been found often. With treatment & cure of HCV comes a responsibility that these at-risk individuals, IDUs or a history of IDU, are educated not to be re-infected. Resources are scarce and should not be wasted particularly in the developing & undeveloped world but also in Europe, the USA & the Western world, its possible that retreatment may be denied by government or payers.

High incidence of hepatitis C virus reinfection within a cohort of injecting drug users - (10/13/13)

HCV Reinfection - (10/11/13)

HCV superinfection and reinfection - Review - (10/10/13)

HCV reinfection incidence and treatment outcome among HIV-positive MSM in London - (06/17/13)

---------------------------

Injection behaviors among injection drug users in treatment: The role of hepatitis C awareness

Highlights

->38.5% of 244 IDUs seeking treatment reported sharing needles/syringes. ->Only 46.9% of IDUs always used a sterile needle/syringe. ->37.7% of IDUs reported being HCV positive. ->HCV awareness was associated with increased risky injection behaviors. ->New HCV prevention interventions are needed for IDUs seeking treatment.

"one's belief about one's HCV status is conceptually more closely related to injection behaviors than biologically confirmed HCV status......IDUs may adopt more of a fatalistic attitude toward risky injection practices. Indeed, a recent synthesis of qualitative studies of HCV risk among IDUs identified risk ubiquity as a common theme, supporting a perception of HCV as "a risk accepted rather than avoided.....The observed multivariable association between knowledge of HCV status and syringe/needle sharing may reflect overall greater drug use severity among those who become HCV-infected rather than a causal pathway toward increased risky behaviors. Regardless, the association highlights the role of HCV awareness as a marker for IDUs in particular need of harm reduction interventions.....The observed association between HCV-awareness and increased needle/syringe sharing may reflect a complex cluster of characteristics among HCV-aware IDUs in this cross-sectional study. Our data support that HCV awareness is likely a marker for IDUs with greater addiction severity (e.g., increased heroin injection and methadone maintenance among HCV-aware), addiction duration (older age among HCV-aware), and increased opportunities for HCV testing (e.g., increased needle exchange program use among HCV-aware, many of which offer HCV testing)."

"Risky injection practices persist among IDUs, with rates in the current study consistent with those of other recent studies (Booth et al., 2011 and Centers for Disease Control and Prevention, 2009) and may partially explain persistently high HCV incidence among IDUs.......In adjusted analysis (Table 2), recent syringe/needle sharing was more likely among those who reported they were HCV-positive compared with those who were HCV negative/unaware (aOR 2.37 [95% CI 1.15, 4.88]), and among IDUs obtaining needles from the street, using any opioids, marijuana, or injected crack cocaine; sharing was less likely among males and participants with some college education......More HCV-positive IDUs reported recent syringe/needle sharing compared with those with HCV negative/unknown status (44.6% vs. 38.5%, p = .131), though this was not statistically significant......The majority of IDUs in the present study obtained needles from safe sources, including pharmacies and syringe exchange programs, as corroborated in surveys of IDUs in other U.S. cities with policies that increase availability of sterile needles and syringes......Despite this, fewer than half of IDUs reported always using a clean needle or consistently cleaning needles, indicating that needle re-use and lack of needle cleaning are common. Even among the minority of IDUs reporting consistent needle cleaning, sterilization techniques other than use of bleach were frequently employed, suggesting that renewed efforts are needed to promote harm reduction techniques among IDUs.......Participants who reported they were HCV positive differed in several important behaviors compared with their counterparts. HCV positive IDUs more frequently exhibited harm reduction behaviors such as obtaining needles from a syringe exchange program, cleaning needles with bleach, and avoiding drinking alcohol to intoxication, suggesting that awareness of HCV status may confer increased adoption of some protective behaviors. HCV positive IDUs, however, were also more likely to inject heroin and, in multivariable analysis, to share needles."

"This finding contrasts with a sero-survey of street-recruited IDUs in Denver from 1998 to 1999, where those with a previous HCV positive test reported less receptive syringe/needle sharing, sharing of drug paraphernalia, and safer injecting practices compared with those with unknown status who tested HCV-positive during the study (Kwiatkowski et al., 2002). It is possible that in populations where higher proportions of IDUs are aware they are HCV-positive, IDUs may adopt more of a fatalistic attitude toward risky injection practices. Indeed, a recent synthesis of qualitative studies of HCV risk among IDUs identified risk ubiquity as a common theme, supporting a perception of HCV as "a risk accepted rather than avoided" (Rhodes, Singer, Bourgois, Friedman, & Strathdee, 2005). This is consistent with findings from a multicenter study of Swedish IDUs, in which 74% of those HCV-aware shared needles compared with 68% of those with unknown status (Norden et al., 2009)."

Author's CONCLUSIONS: This study highlights the need for broadly implemented HCV prevention interventions for all IDUs seeking addiction treatment, and suggests such interventions might particularly decrease transmission behaviors by those aware of their HCV infection and prevent HCV infection in those HCV-negative/unaware. Research which prospectively studies the effect of HCV testing and notification on risk behavior could help further clarify the association between HCV awareness and risk behaviors. Interventions that could improve services for IDUs include those that explicitly and repeatedly educate IDUs about safer injection practices and the treatability of HCV, and those that integrate HCV testing and treatment with addiction treatment services. As HCV screening and treatment options advance, community based treatment programs have a greater opportunity to play a central role in reducing HCV transmission and engaging HCV-infected IDUs in treatment.

-------------------------------

Injection behaviors among injection drug users in treatment: The role of hepatitis C awareness

Addictive Behaviors April 2012

P. Todd Korthuis a,, Daniel J. Feaster b, Zoilyn L. Gomez b, Moupali Das c,d, Susan Tross e, Katharina Wiest f, Antoine Douaihy g, Raul N. Mandler h, James L. Sorensen c, Grant Colfax d, Dennis McCarty a, Stephanie E. Cohen d, Patricia E. Penn i, Diane Lape a, Lisa R. Metsch b
a Department of Medicine and Department of Public Health and Preventive Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
b Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, 1425 Northwest 10th Ave, 3rd floor, Miami, FL 33136, USA c University of California, San Francisco, 1001 Potero Ave., San Francisco, CA 94110, USA
d San Francisco Department of Public Health, 356 7th St., San Francisco, CA 94103, USA
e HIV Center For Clinical and Behavioral Studies, NYS Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA
f CODA, 1027 East Burnside St., Portland, OR 97214, USA
g University of Pittsburgh School of Medicine, 3811 O'Hara St # 1059, Pittsburgh, PA 15213, USA
h National Institute on Drug Abuse, National Institutes of Health, 6001 Executive Blvd., Bethesda, MD 20892, USA
i La Frontera Arizona, 504 W. 29th St., Tucson, AZ 85713, USA

Abstract

Background

Injection drug use (IDU) is a primary vector for blood-borne infections. Awareness of Hepatitis C virus (HCV) infection status may affect risky injection behaviors. This study determines the prevalence of risky injection practices and examines associations between awareness of positive HCV status and risky injection behaviors.

Methods

We surveyed individuals seeking treatment for substance use at 12 community treatment programs as part of a national HIV screening trial conducted within the National Drug Abuse Treatment Clinical Trials Network. Participants reported socio-demographic characteristics, substance use, risk behaviors, and HCV status. We used multivariable logistic regression to test associations between participant characteristics and syringe/needle sharing.

Results

The 1281 participants included 244 (19.0%) individuals who reported injecting drugs in the past 6 months and 37.7% of IDUs reported being HCV positive. During the six months preceding baseline assessment, the majority of IDUs reported obtaining sterile syringes from pharmacies (51.6%) or syringe exchange programs (25.0%), but fewer than half of IDUs always used a sterile syringe (46.9%). More than one-third (38.5%) shared syringe/needles with another injector in the past 6 months. Awareness of positive HCV vs. negative/unknown status was associated with increased recent syringe/needle sharing (aOR 2.37, 95% CI 1.15, 4.88) in multivariable analysis.

Conclusions

Risky injection behaviors remain prevalent and awareness of HCV infection was associated with increased risky injection behaviors. New approaches are needed to broadly implement HCV prevention interventions for IDUs seeking addiction treatment.

1. Introduction

Injection drug use (IDU) is the primary driver for Hepatitis C virus (HCV) transmission, accounting for the majority of chronic HCV infections in the U.S. (Alter, 1999 and Armstrong et al., 2006). Across multiple U.S. studies, 35-65% of current IDUs report risky injection behaviors such as syringe/needle sharing (Bailey et al., 2007, Booth et al., 1998, Centers for Disease Control and Prevention, 2009 and Golub et al., 2007).

Knowledge of harboring a transmissible infection such as HCV may influence risky behaviors. Prior studies of the effects of HCV-infection awareness on risky behaviors demonstrate mixed results. In a serosurvey of out-of-treatment IDUs, those who reported awareness of HCV-infection engaged in fewer risky behaviors compared with those who were unaware (Kwiatkowski, Fortuin Corsi, & Booth, 2002). HCV-aware IDUs may also "sero-sort," or preferentially engage in risky injection behaviors with others they know to be similarly HCV-infected (Burt, Thiede, & Hagan, 2009). Other studies, however, suggest that HCV awareness is insufficient to change injection risk behaviors (Norden et al., 2009). Little is known about the influence of HCV awareness on IDUs engaged in substance use treatment-information that might improve HCV prevention services in addiction treatment settings.

The purpose of this analysis was to 1) assess the prevalence and correlates of drug use practices among patients presenting for addiction treatment and 2) compare risky behaviors in those reporting HCV-infection with those who reported negative or unknown HCV status.

2. Methods

2.1. Design and setting

The primary study was a National Drug Abuse Treatment Clinical Trials Network (CTN) trial comparing the effectiveness of strategies to increase HIV testing (Metsch et al., in press). Between January and May 2009, the trial randomized 1281 individuals receiving addiction treatment at 12 geographically diverse, community-based addiction treatment programs. After providing informed consent, participants completed an audio computer assisted self interview recording substance use behaviors.

2.2. Participants

Participants receiving addiction treatment were eligible for enrollment if they were 1) ³ 18 years old, 2) reported unknown or negative HIV status, and 3) had not been tested and received results for HIV within the last 12 months. The current analysis was restricted to the 244 participants who reported IDU in the six months preceding the study baseline assessment.

2.3. Measures

Participants were asked about injection risk behaviors over the prior six months using items from Project Inspire (Purcell et al., 2004) and the NIDA Risk Behavior Assessment survey (Needle et al., 1995) including source of syringes, needle cleaning practices, how they cleaned their needles, and recent syringe/needle sharing (the main dependent variable). Participants reported injection and non-injection drug use and drinking alcohol to intoxication in the past 6 months (Colfax et al., 2004).

The independent variable was self-reported HCV infection awareness. Patients were asked, "Have you ever been diagnosed with hepatitis C (yes, no, don't know)?" Because there was no difference in syringe/needle sharing between participants who reported they were HCV-negative and those who did not know their HCV status, we dichotomized this variable as HCV-positive vs.

HCV-negative/unknown. Covariates included age, gender, race/ethnicity, employment, education, court-mandated treatment, opioid replacement treatment, and whether or not the patient had been jailed in the last 6 months.

2.4. Analysis

Descriptive statistics characterized participant socio-demographics, and substance use behaviors. We assessed bivariate and multivariable associations between participant characteristics and any syringe/needle sharing using logistic regression. Variables were included in the multivariable logistic regression model if associated with syringe/needle sharing in univariate analyses (p < .20), or on the basis of a priori hypotheses. Potential interactions were assessed.

3. Results

3.1. Participant characteristics

Of 244 recent IDUs, 60.7% were men, 66.0% white, 14.3% Hispanic, and 10.2% Black race/ethnicity, with a mean age of 39.3 (SD = 11.0) years. Twenty percent were employed, 36.2% had attained at least some college education, 30.3% had been recently incarcerated, 20.1% were receiving court-mandated treatment and 46.7% opioid replacement therapy. Ninety-two IDU (37.7%) reported being positive for HCV, 55 (22.5%) HCV-negative, and 97 (39.8%) unknown HCV status. Compared with those who were HCV negative/unaware, HCV positive IDUs were older (45.3 vs. 35.6 years, p < .001), more likely to be women (52.2% vs. 31.6%, p = .001) or enrolled in opioid replacement programs (68.5% vs. 33.6%, p < .001) and less likely to be recently incarcerated (21.7% vs. 35.5%, p = .023).

The most commonly used substances were injected opioids (71.17%), drinking alcohol to intoxication (70.9%), non-injection opioids (66.4%), marijuana (48.8%), crack cocaine (45.1%), and cocaine (30.7%). The majority of IDUs (81.1%) injected more than one substance at a time. HCV positive IDUs were less likely to drink alcohol to intoxication (57.6% vs. 78.9%, p < .001) but more likely to inject heroin (68.5% vs. 55.3%, p = .041) compared with HCV negative/unaware.

3.2. Injection risk behaviors

More than one third (38.5%) of IDUs reported syringe/needles sharing in the past 6 months (Table 1). IDUs obtained needles mostly from pharmacies, syringe exchange programs, and diabetic supplies. Less than half always used a clean needle. Among IDUs who cleaned their needles, cleaning with bleach was the most common method, but many used more ineffective sterilization methods including soap and water. More HCV-positive IDUs reported recent syringe/needle sharing compared with those with HCV negative/unknown status (44.6% vs. 38.5%, p = .131), though this was not statistically significant. There was no difference in recent syringe/needle sharing between those who reported being HCV negative vs. unknown status (36.4% vs. 34.0%, p = .771). HCV positive IDUs more frequently obtained needles from a syringe exchange program and used bleach if they cleaned needles.

In adjusted analysis (Table 2), recent syringe/needle sharing was more likely among those who reported they were HCV-positive compared with those who were HCV negative/unaware (aOR 2.37 [95% CI 1.15, 4.88]), and among IDUs obtaining needles from the street, using any opioids, marijuana, or injected crack cocaine; sharing was less likely among males and participants with some college education.

4. Discussion

Risky injection practices persist among IDUs, with rates in the current study consistent with those of other recent studies (Booth et al., 2011 and Centers for Disease Control and Prevention, 2009) and may partially explain persistently high HCV incidence among IDUs (Mehta et al., 2011). In a survey of IDUs in 23 U.S. cities from 2005 to 2006, 31.8% of IDUs reported sharing needles (Centers for Disease Control & Prevention, 2009). Among IDUs enrolling in a behavioral intervention trial (2-session HIV/HCV counseling vs. therapeutic alliance vs. treatment as usual) at residential detoxification centers from 2004 to 2006, 61% reported sharing needles, works, or drug solution (Booth et al., 2011). More widespread adoption of interventions demonstrated to reduce risky injection practices, and development of new, more effective interventions, are urgently needed for patients enrolling in community-based treatment programs.

The majority of IDUs in the present study obtained needles from safe sources, including pharmacies and syringe exchange programs, as corroborated in surveys of IDUs in other U.S. cities with policies that increase availability of sterile needles and syringes (Golub et al., 2005 and Khoshnood et al., 2000) - policies that decrease HIV transmission and likely decrease HCV transmission, as well (Des Jarlais et al., 1996 and Des Jarlais et al., 2000). Despite this, fewer than half of IDUs reported always using a clean needle or consistently cleaning needles, indicating that needle re-use and lack of needle cleaning are common. Even among the minority of IDUs reporting consistent needle cleaning, sterilization techniques other than use of bleach were frequently employed, suggesting that renewed efforts are needed to promote harm reduction techniques among IDUs. Interventions that promote needle cleaning such as peer-based (Hawkins et al., 1999 and Rietmeijer et al., 1996), pharmacy-based (Romanelli, Smith, & Pomeroy, 2000), and provider-based (Carlson, Wang, Siegal, & Falck, 1998) interventions, continue to be relevant for IDUs engaged in community-based treatment. At the same time, renewed efforts to increase availability of clean syringe/needles are urgently needed to decrease HCV transmission.

Participants who reported they were HCV positive differed in several important behaviors compared with their counterparts. HCV positive IDUs more frequently exhibited harm reduction behaviors such as obtaining needles from a syringe exchange program, cleaning needles with bleach, and avoiding drinking alcohol to intoxication, suggesting that awareness of HCV status may confer increased adoption of some protective behaviors. HCV positive IDUs, however, were also more likely to inject heroin and, in multivariable analysis, to share needles. The observed association between HCV-awareness and increased needle/syringe sharing may reflect a complex cluster of characteristics among HCV-aware IDUs in this cross-sectional study. Our data support that HCV awareness is likely a marker for IDUs with greater addiction severity (e.g., increased heroin injection and methadone maintenance among HCV-aware), addiction duration (older age among HCV-aware), and increased opportunities for HCV testing (e.g., increased needle exchange program use among HCV-aware, many of which offer HCV testing).

This finding contrasts with a sero-survey of street-recruited IDUs in Denver from 1998 to 1999, where those with a previous HCV positive test reported less receptive syringe/needle sharing, sharing of drug paraphernalia, and safer injecting practices compared with those with unknown status who tested HCV-positive during the study (Kwiatkowski et al., 2002). It is possible that in populations where higher proportions of IDUs are aware they are HCV-positive, IDUs may adopt more of a fatalistic attitude toward risky injection practices. Indeed, a recent synthesis of qualitative studies of HCV risk among IDUs identified risk ubiquity as a common theme, supporting a perception of HCV as "a risk accepted rather than avoided" (Rhodes, Singer, Bourgois, Friedman, & Strathdee, 2005). This is consistent with findings from a multicenter study of Swedish IDUs, in which 74% of those HCV-aware shared needles compared with 68% of those with unknown status (Norden et al., 2009).

The current study confirms the importance of certain demographic and drug use characteristics previously associated with syringe/needle sharing including younger age, female gender, lower educational attainment, and use of opiates, and crack cocaine. While greater addiction severity is associated with riskier injection behaviors, the current study is among the first to identify an association between marijuana use and risky injection behaviors. Marijuana use in IDUs may be a marker of risk-taking personality or chronically decreased motivation to protect oneself, as hypothesized to explain similar findings in a study of Russian IDUs (Walley et al., 2008). Further research is required to assess the nature of this association.

This study has limitations. First, our study population was recruited from individuals seeking or actively engaged in treatment in community-based treatment programs. Findings may not be generalizable to IDUs in other settings. Second, HCV status was assessed by self-report and likely underestimates the actual prevalence of HCV. However, one's belief about one's HCV status is conceptually more closely related to injection behaviors than biologically confirmed HCV status. Third, we were unable to assess sero-sorting in the current study, so increased sharing among HCV may have been with other known HCV-positive IDU, as was observed in one prior study (Burt et al., 2009). Finally, the current study's cross-sectional design limits our ability to infer causality. The observed multivariable association between knowledge of HCV status and syringe/needle sharing may reflect overall greater drug use severity among those who become HCV-infected rather than a causal pathway toward increased risky behaviors. Regardless, the association highlights the role of HCV awareness as a marker for IDUs in particular need of harm reduction interventions.

5. Conclusions

This study highlights the need for broadly implemented HCV prevention interventions for all IDUs seeking addiction treatment, and suggests such interventions might particularly decrease transmission behaviors by those aware of their HCV infection and prevent HCV infection in those HCV-negative/unaware. Research which prospectively studies the effect of HCV testing and notification on risk behavior could help further clarify the association between HCV awareness and risk behaviors. Interventions that could improve services for IDUs include those that explicitly and repeatedly educate IDUs about safer injection practices and the treatability of HCV, and those that integrate HCV testing and treatment with addiction treatment services. As HCV screening and treatment options advance, community based treatment programs have a greater opportunity to play a central role in reducing HCV transmission and engaging HCV-infected IDUs in treatment.

Role of funding source

This work was supported by the National Institute on Drug Abuse which supported the design, distribution, collection and analysis of the clinical trial. The final version of the manuscript was reviewed and approved by the NIDA Clinical Trials Network publications committee.

Source

Patient Advocate Foundation Announces Co-Pay Relief (CPR) Support for Patients Living with Hepatitis C

The launch of the CPR Silo for Hepatitis C Patients Will Provide Financial Assistance to Patients in Need

HAMPTON, Va., Feb. 5, 2014 /PRNewswire-USNewswire/ -- Patient Advocate Foundation (PAF) announced today the expansion of its Co-Pay Relief (CPR) program with the opening of the Hepatitis C disease silo. Supported through a generous donation of5 million dollars, this CPR program silo providers financial support for pharmaceutical co-payments for insured patients who are facing financial distress and are unable to afford their costs associated with treatment for the virus. "Management of Hepatitis C is extremely challenging for patients as most need ongoing medication to reduce their chance of liver damage or liver cancer.  It is in these cases that a patient's survival and overall health can be jeopardized if he or she is unable to access pharmaceutical treatment and therapies required to control the virus," said Alan Balch, PhD,  CEO of PAF. "We are grateful for the significant support we have received for the Hepatitis C silo which allows us to expand our Co-Pay Relief Program in such a meaningful way."  The donation allows PAF to provide financial support to Hepatitis C patients ensuring their access to the treatments that can restore balance to their health and markedly improve their quality of life.  Qualified patients whose applications are approved, are eligible for up to $3,000 per year in copayment assistance through the program.

PAF is a pioneer in the field of copayment support programs, providing more than $190 million in financial assistance to more than 95,000 patients who would have been otherwise unable to afford their pharmaceutical co-payments since 2004. The program provides this support to insured patients who financially and medically qualify including those covered by government sponsored insurance programs such as Medicare, Medicaid or Tricare.  

For more information about PAF's Co-Pay Relief program and the options for assistance for Hepatitis C patients, visit http://www.copays.org/diseases/hepatitis-c or call 866-512-3861.

About the Patient Advocate Foundation (PAF) Co-Pay Relief Program (CPR)

The Co-Pay Relief Program, a division of Patient Advocate Foundation, provides direct financial support for pharmaceutical co-payments to insured patients who financially and medically qualify.

The program offers innovative technology tools for patients, providers and pharmacy representatives including 24 hour web based application portals, electronic signature, document upload and bar code fax routing capabilities, increasing the speed with which an approval can be granted and expenditure can be paid.  Keeping with Patient Advocate Foundation's emphasis on patient-centric service, the program also offers individualized assistance to all patients through trained, professional staff who personally guide them through the enrollment process. 

For more information or to contact Patient Advocate Foundation's Co-Pay Relief program visit www.copays.org or 1-866-512-3861

SOURCE Patient Advocate Foundation

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