April 16, 2012

Hepatitis B runs rampant in BC's large Asian community

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Dr. Eric Yoshida, Gastroenterologist at UBC (Erin Loxam, News1130)

Doctors urge early testing to prevent cirrhosis or liver cancer

Erin LoxamApr 16, 2012 12:51:44 PM

VANCOUVER (NEWS1130) - Hepatitis B (HBV) is proving to be a huge medical problem for the large Asian community in the Vancouver area. BC already has an estimated 60,000 patients and many others are undetected.

Many are diagnosed very late in the disease - once they already have cirrhosis or liver cancer.

Dr. Eric Yoshida, Gastroenterologist at UBC, says many people come to Canada, not even knowing they are a carrier of HBV.

"Around the world it's passed from mother to child. It is not because you scored drugs, it's not because you had affairs sexually, or things like that. You got it because you were born. End of story. There should be no stigma about Hepatitis B."

But he says there is. Trying to find someone among his patients with the disease to talk publicly about their experiences was nearly impossible.

HBV rates in Vancouver, Richmond and Surrey are approaching that of Asia and treatment is necessary to keep worse conditions at bay.

"We have these great anti-viral agents, which are only wonderful if people can actually take them. They cost a lot of money."

"If I tell my patients they need to go on these expensive drugs, I'm not telling them they need to go on these expensive drugs because I like writing prescriptions, or I'm supporting the pharmaceutical industry. I'm telling them they need these drugs because if they don't take these drugs, then I can't guarantee that something bad may not happen in the next five to 10 years," explains Dr. Yoshida.

Twenty-five per cent of people with HBV currently die from related diseases. Cirrhosis and liver cancer are huge strains on the BC healthcare system and could be avoided earlier on.

Doctors doing blood work need to order the test for HBV when looking for other problems in people in the Asian community.

Yoshida thinks things are better than they were 20 years ago, but they are still losing the battle against this deadly disease.

Yoshida and SUCCESS want more awareness and increased resources for early diagnosis, which is a simple blood test. He's also pushing for coverage for treatment from the BC Government.

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PRESS RELEASE

April 16, 2012, 9:01 a.m. EDT

NEWTON, Mass., Apr 16, 2012 (BUSINESS WIRE) -- Galectin Therapeutics, the leading developer of therapeutics that target galectin proteins to treat fibrosis and cancer, today announced that it will present at Digestive Disease Week May 19-22, 2012, in San Diego, CA. Peter G Traber, MD, President, CEO and CMO of Galectin, will present "Galectin Inhibition: a Promising New Strategy to Treat NASH and Liver Fibrosis" at the Product Theater on May 21, 2012, at 2 pm PT. Dr. Traber will discuss the role of galectins in the pathogenesis of non-alcoholic steatohepatitis (NASH), also known as fatty liver disease, and how the Company's galectin inhibitor compounds have been efficacious in preclinical models of disease. The broad effect of galectin inhibitors in preclinical models on all parameters of NASH liver injury, including fat deposition, liver cell death, inflammation and fibrosis makes this class of compounds particularly attractive drug candidates. In addition, Galectin Therapeutics will host Booth #3424 in Exhibit Hall E.

"We believe that our preclinical results suggest that galectin inhibition may be a robust and novel therapy for NASH and liver fibrosis, conditions for which there are no currently approved therapies," said Dr. Traber. "Presentation of our preclinical results at DDW provides exposure to the world's largest gathering of physicians and researchers in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery."

About NASH NASH is a common disease of the liver, affecting 9 to 15 million people in the United States and is characterized by the presence of fat in the liver along with inflammation and damage in people who drink little or no alcohol. Over time, patients with NASH can develop fibrosis, or scarring of the liver, that can lead to cirrhosis, a severe liver disease where transplantation is the only current treatment available. Galectin Therapeutics is developing drug candidates as an alternative to transplantation and lead candidates have reversed fibrosis in preclinical disease models.

About Galectin Therapeutics Galectin Therapeutics is developing promising carbohydrate-based therapies for the treatment of fibrotic liver disease and cancer based on the Company's unique understanding of galectin proteins, key mediators of biologic function. We are leveraging extensive scientific and development expertise as well as established relationships with external sources to achieve cost effective and efficient development. We are pursuing a clear development pathway to clinical enhancement and commercialization for our lead compounds in liver fibrosis and cancer. Additional information is available at www.galectintherapeutics.com .

Forward Looking Statements This press release contains, in addition to historical information, forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements relate to future events or future financial performance, and use words such as "may," "estimate," "could," "expect" and others. They are based on our current expectations and are subject to factors and uncertainties which could cause actual results to differ materially from those described in the statements. Factors that could cause our actual performance to differ materially from those discussed in the forward-looking statements include, among others: incurrence of operating losses since our inception, uncertainty as to adequate financing of our operations, extensive and costly regulatory oversight that could restrict or prevent product commercialization, inability to achieve commercial product acceptance, inability to protect our intellectual property, dependence on strategic partnerships, product competition, and others stated in risk factors contained in our SEC filings. We cannot assure that we have identified all risks or that others may emerge which we do not anticipate. You should not place undue reliance on forward-looking statements. Although subsequent events may cause our views to change, we disclaim any obligation to update forward-looking statements.

SOURCE: Galectin Therapeutics

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Project Walks Primary Care Providers Through Toughest Cases

By: SHERRY BOSCHERT, Family Practice News Digital Network

On 5 p.m. on the day before Thanksgiving, Dr. Alan Caroe, a general practitioner in Las Cruces, N.M., had to decide whether to prescribe an opiate medication to "a very smooth individual from out of town who had a story that was just barely plausible."

Dr. Caroe felt he had insufficient expertise in opioid management, an area that’s complex and difficult and fraught with risk but also an opportunity to help patients in chronic pain, he said in an interview. He needed a quick consultation, but who would answer the phone on that day, at that hour?

Experts at the chronic pain and headache clinic at Project ECHO (Extension for Community Healthcare Outcomes), that’s who. They walked him through the complex issues in the case, which led him to retract an opiate prescription that he initially had phoned into a pharmacy for this patient.


Real-time consultations are only a part of Project ECHO, an award-winning program based at the University of New Mexico in Albuquerque. In addition, the program provides weekly videoconferences, not only to discuss cases but also to educate and mentor community physicians to take on frontline management of chronic diseases in their geographic areas.

The aim is to act as a multiplier, and to expand the health system’s capacity to manage common, chronic, but complex diseases, Dr. Sanjeev Arora explained in a presentation at the annual meeting of the American Academy of Pain Medicine. New Mexico’s 1.8 million people are spread across 121,000 square miles, and 32 of the state’s 33 counties are listed as medically underserved areas.

Project ECHO began with a focus on improving the care of patients with hepatitis C, and its success has spawned Project ECHO programs for asthma, rheumatology, HIV infection, cardiac risk reduction, chronic pain management, geriatrics, palliative care, substance abuse, prevention of teenage suicide, high-risk pregnancy, childhood obesity, child psychiatry, psychotherapy, antibiotic stewardship, and ethics consultation. More than 400 clinical sites can now connect with Project ECHO.

The Project ECHO model has been cloned by the University of Washington in Seattle, the U.S. Veterans Health Administration, the U.S. Department of Defense, and the country of India, among other entities. The focus is not just on helping rural areas; the University of Chicago’s project works with urban physicians in the community to improve the care of black patients with difficult-to-treat hypertension, whose numbers would overwhelm the limited number of specialists.

When the project’s director, Dr. Arora, a gastroenterologist and hepatologist, founded Project ECHO in 2002, an estimated 28,000 people in the state had hepatitis C, and patients faced an 8-month waiting list to be seen at Dr. Arora’s specialty clinic, which often required traveling long distances. The project has conducted more than 500 "telehealth clinics" on hepatitis C, and has helped get more than 5,000 patients into hepatitis C treatment who previously had no access to care, said Dr. Arora, a professor of medicine at the University of New Mexico.

"We want to transform the nature of what primary care looks like in the United States," he said.

The quality of care these patients are getting in the community rivals the quality at the university, and minorities’ access to care is expanding, a prospective study of 407 patients found. A sustained viral response to treatment for hepatitis C was achieved in 58% of patients managed at the university and by 58% of patients managed by primary care physicians at rural and prison sites who participated in Project ECHO (N. Engl. J. Med. 2011;364:2199-2207). Response rates to different subtypes of hepatitis C also did not differ significantly between the two groups.

 Patients who received care at the Project ECHO community sites, however, were significantly more likely to be racial/ethnic minorities (68%), compared with the university’s patients (49%), he said. The cure rate at community sites was significantly higher than cure rates reported in previous community-based studies of hepatitis C treatment, which hovered around 20%, he added. This may be a result of Project ECHO’s emphasis on best-practices protocols and other attributes.

"Project ECHO has brought so much balance. We’ve reduced variation in prescribing" practices for pain medications, for example, Dr. Joanna G. Katzman said in a separate presentation at the meeting. "The degree to which people have evolved blows my mind."

Dr. Katzman, director of Project ECHO’s chronic pain and headache clinic and a neurologist at the University of New Mexico, said that her weekly videoconference typically starts at noon so that primary care physicians can join in during their lunch break. Participants get free CME credits.

The project’s interdisciplinary team of experts and remote participants spend the first half-hour reviewing and discussing three or four cases that have been faxed in by remote participants, followed by 25-30 minutes of didactic presentations. A second hour covers more cases, for those who can stay on. Once a month, the videoconference includes a skills demonstration, such as a trigger point examination or a procedure. Community physicians who miss the live videoconference can watch a video of it later.

"It’s the best use of lunchtime that you can consider," said Dr. Caroe, the generalist in Las Cruces.

Since starting in 2009, Project ECHO’s chronic pain and headache clinic sessions have attracted 474 participants in 168 locations in multiple states, averaging more than six sessions per attendee. In all, 42% are physicians, 23% are nurses or physician assistants, and 35% are others including pharmacists and chiropractors.

Physician assistant Debra Newman worked for several years as a community health extension agent at a rural clinic in Espanola, N.M., with part of her salary paid by the clinic and part by Project ECHO. She managed hundreds of patients who were referred to her for everything from simple low back pain to fibromyalgia, rheumatoid arthritis, and failed back surgery syndrome.

"After sitting in on Project ECHO for years, I could manage many of these patients on my own," said Ms. Newman, now of Christus St. Vincent Regional Medical Center in Santa Fe, N.M. As a P.A., she could practice independently if a supervising physician was within 100 miles – but, she said, she still took complex cases to the teleconference for consultations.

Project ECHO is funded by grants from state and federal government sources and the Robert Wood Johnson Foundation. Large health care systems are cloning the model because they see that it’s a cost-effective way to provide specialty services to more patients without transferring them to specialty care, Dr. Arora said.

"It isn’t expensive if you think that you’re training someone out there to replace you," Dr. Rollin M. Gallagher said in a separate presentation at the meeting. Project ECHO inspired the creation of the similarly-modeled Veterans Affairs SCAN (Specialty Care Access Network), said Dr. Gallagher, deputy national program director for pain management in the Veterans Health Administration and director for pain policy and primary care research at Penn Pain Medicine at the University of Pennsylvania, Philadelphia.



Dr. Ilene R. Robeck runs what she calls a "poor man’s Project ECHO" that provides pain management education, mentoring, and consultations primarily to physicians at three Veterans Affairs medical centers in Florida. "As much as I thought [Project ECHO] was a fantastic program, the resources needed were really higher than the resources I had," she said in an interview.

Funded by a federal grant through September 2013, her project offers a weekly telephone audioconference and immediate access to expert consultations by phone – initiatives that stress the education of participants as much as individual case consultations.

"The results have been overwhelmingly positive," with close to 100 health care providers now calling in from VA facilities around the country each week, said Dr. Robeck of Bay Pines (Fla.) Veterans Affairs Healthcare System.

When Dr. Caroe first heard about Project ECHO, he listened to the weekly conferences by phone because the Internet connection for videoconferencing was too slow where he was practicing in Chaparral, N.M. He now videoconferences each week on a faster connection at his current practice in Las Cruces.

The nearest pain specialists are in Albuquerque (about 260 miles away and too far for many patients to travel for routine visits) or in El Paso, Tex. Crossing state lines for care can create problems with insurance.

He has no doubt that the skills he has gained through Project ECHO have benefited his patients. One 49-year-old female engineer had suffered nearly a lifetime of terrible migraine headaches. Prior to Project ECHO’s didactic and clinical presentations, Dr. Caroe had never heard of premenstrual migraine, and the patient had never noticed that her headaches regularly got worse 2 days before the start of her menstrual period.

"She went from monthly hell" to treatment with a low-dose, short-term estrogen patch to get her through her 4-day period of risk, he said. When she came in for a follow-up visit recently, she told him, "You changed my life."

Dr. Arora has received research funding from Genentech, Gilead, Pharmasset, Tibotec, Vertex, and ZymoGenetics. The other people interviewed for this story reported having no financial disclosures.

Heroin vaccine won't 'cure' what ails addicts

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For nearly 40 years scientists have been working on vaccines against all kinds of addictions, including nicotine, marijuana and alcohol. (Illustration by Wes Bausmith / Los Angeles Times)

Even if it proves effective, it can't cure the underlying factors that make people prone to drug use, including poverty, violence and lack of opportunity.

April 15, 2012 | By Angela Garcia

My aunt Marion is in the hospital dying of liver and kidney failure, the result of her 20-year struggle with heroin use. I was told of her imminent death the same day news broke about a vaccine against the drug. "Breakthrough heroin vaccine could render drug 'useless' in addicts," one headline read. "Scientists create vaccine against heroin high," proclaimed another.

Meanwhile, my aunt finds temporary relief in the ever more frequent administration of opiate pain medication — the very kind of drugs she used illegally.

The idea of an anti-addiction vaccine is not new. For nearly 40 years scientists have been working on vaccines against all kinds of addictions, including nicotine, marijuana and alcohol. There are even trials of vaccines to prevent obesity. None of the anti-addiction vaccines has yet received Food and Drug Administration approval, however, and most of the studies are still in their early stages.

The headlines trumpeting a heroin vaccine were based on a finding that the drug had proved to be effective on mice during trials in Mexico (a nation that could use some good news related to drugs). Scientists now plan to test the patented vaccine in humans. If all goes well, the vaccine could be available in five years — too late for my aunt but providing a glimmer of hope for the estimated 1 million heroin addicts in the United States. Perhaps.

Six years ago, when I was a doctoral student researching heroin addiction in northern New Mexico, I received an email from a scientist studying a possible vaccine against the drug's use. The study was in rat models, but early results were promising and suggested the likelihood of a therapeutic effect for humans. Aware of the devastating heroin epidemic in New Mexico, which had the highest rate of heroin-related deaths in the Unites States, and of my work trying to understand it, the scientist wanted to offer some hope. He wrote that he could imagine a time when heroin addiction, in New Mexico and around the world, would be a thing of the past. I wanted to believe him, but I was less optimistic.

As an anthropologist with personal ties to the problem of addiction, I have studied the social and historical influences of drug use, and that has made me skeptical about the idea of a vaccine. Entrenched poverty, social inequality and personal despair all promote drug use, and these things profoundly shape the unequal outcomes of the addicted. Where I lived and worked, illicit drugs were more available than mental health services, and heroin was often used as a "medicine" to relieve the suffering of everyday life.

On the afternoon of the scientist's email, I returned to the drug recovery clinic where I worked caring for patients undergoing heroin detox and described the idea of a vaccine against addiction to my colleagues. Jose, a drug counselor with a portrait of Jesus tattooed on his needle-scarred forearm, called it science fiction. Monica, the clinic's cook, doubted that such advances, if they actually materialized, would ever benefit the tecatos of northern New Mexico. She pointed out that the clinic could barely afford day-old tortillas, much less expensive new vaccines. We dismissed the idea and returned to addressing the day-to-day struggles of our heroin-addicted patients, many of them friends and family.

The development of an anti-addiction vaccine still faces major challenges. In the past, vaccines that were effective in animal models have proved ineffective in humans. This is partly because the molecules introduced into the blood to generate antibodies against the effects of the drug on the brain are incredibly tiny. The human immune system is vastly more complex than that of the animals used for testing, and it tends to simply ignore the vaccine. Scientists are working their way around this problem by attaching proteins and chemicals to the molecules to induce antibody production. Such anti-addiction "vaccine cocktails," as they are ironically called, reflect the growing perception that addiction is a biologically based disease of the brain, making the very idea of a vaccine against addiction plausible.

One problem, though, is that even the most effective anti-addiction vaccine can't cure the underlying factors that make people prone to using drugs, including poverty, violence and lack of opportunity. Rather, the vaccines are aimed at preventing a drug user from experiencing the pleasure associated with a particular drug. When a mouse no longer feels pleasure from a drug because of a vaccine, it doesn't have the option of turning to another pleasure-producing substance. But humans do. A vaccine against pleasure derived from one kind of drug use might well spawn other forms of pleasure-seeking, especially when the drugs were being used in an attempt to relieve suffering.

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PRESS RELEASE

April 16, 2012, 8:30 a.m. EDT

UnitedHealthcare is first health care company to partner with the AGA Digestive Health Outcomes Registry(R) to help advance high-quality, cost-effective medical best practices

MINNETONKA, Minn., Apr 16, 2012 (BUSINESS WIRE) -- --Technology platform from MedAssurant, Inc., to gather and analyze data

UnitedHealthcare and the American Gastroenterological Association (AGA) today announced a collaboration designed to improve patient care and outcomes in digestive disorders.

Through this collaboration, UnitedHealthcare will incorporate gastroenterologist (GI) physician data from the AGA Digestive Health Outcomes Registry(R) into its physician performance measurement programs that compare individual treatment practices with national treatment standards created by gastroenterologists. Data from the registry will support UnitedHealthcare's expanding portfolio of physician incentive programs that reward medical groups and physicians who demonstrate high-quality, cost-effective care.

Information obtained from this analysis will help UnitedHealthcare and the AGA promote best practices related to the care of patients with digestive disorders. The registry is certified by the Centers for Medicare & Medicaid Services (CMS), enabling practices to submit data on Medicare beneficiaries with hepatitis C to the CMS Physician Quality Reporting System.

UnitedHealthcare is the first health care company to partner with the AGA Digestive Health Outcomes Registry to help advance high-quality, cost-effective medical best practices

"We support UnitedHealthcare's leadership in promoting quality care and are pleased to partner with them to improve the quality of care that gastroenterologists provide patients," said John I. Allen, M.D., MBA, AGAF, vice president-elect of the AGA Institute and chair of the AGA Registry Executive Management Board. "The AGA Registry is derived from evidence-based clinical guidelines and outcomes measures developed by GI clinicians. It is a powerful tool for gastroenterologists who want to benchmark their practices, proactively manage patient care and ensure the appropriate use of resources."

The AGA Registry has been operational for two years and remains open to new physician members. GI physicians in UnitedHealthcare's care provider network will be able to submit information upon enrollment in the registry.

The AGA Registry contains data from MedAssurant's Medical Outcomes for Research on Economics and Effectiveness Registry(R) (MORE(2) Registry(R)), which includes submissions from practicing gastroenterologists nationwide. MedAssurant's registry division is primarily responsible for the technology platform, collection of information from practicing gastroenterologists, associated analytics, and reporting capabilities to UnitedHealthcare.

"The AGA's national membership of gastroenterologists, together with the combination of our broad national network of 650,000 physicians and other care providers, and our focus on communicating the value of information tied to consumer and physician engagement and incentive programs, enables our organizations to advance safe, timely and effective patient care to improve outcomes," said Sam Ho, M.D., chief clinical officer of UnitedHealthcare. "UnitedHealthcare is committed to working with the AGA and other leading medical organizations to promote the best care possible for patients."

UnitedHealthcare's collaboration with AGA is another example of the company's commitment to help gastroenterologists improve performance and patient care. In 2010, UnitedHealthcare received the Richard L. Doyle Award for Innovation and Leadership in Health Care from Milliman Care Guidelines for working with physicians and other health professionals to identify and employ best practices to prevent complications from major bowel surgery.

Follow this link for more information about the AGA Registry. To learn more about UnitedHealthcare's physician performance measurement programs, visit www.myuhc.com ; for physicians, visit www.unitedhealthcareonline.com .

About the American Gastroenterological Association The American Gastroenterological (GI) Association is the trusted voice of the GI community. Founded in 1897, the American Gastroenterological Association has grown to include 17,000 members from around the globe who are involved in all aspects of the science, practice and advancement of gastroenterology. The AGA Institute administers the practice, research and educational programs of the organization. Learn more at www.gastro.org .

About MedAssurant, Inc. MedAssurant, Inc. is a leading technology-enabled health care solutions provider focused on the importance of health care data and its ability to drive dramatic, objective improvement in clinical and quality outcomes, care management and financial performance throughout the health care community. Proprietary health care datasets, aggregation and analysis capabilities, combined with a national infrastructure of leading-edge technology, clinical prowess and deep human resources, empower MedAssurant's advanced generation of health care assessment and improvement through highly informed solutions. Driven by a mission to improve today's health care landscape, the employees of MedAssurant proudly apply care, ingenuity and dedication to delivering a new approach to health care touching nearly 120 million Americans -- one driven by data and insight -- one resulting in meaningful action. Please visit www.medassurant.com for more information.

About UnitedHealthcare UnitedHealthcare is dedicated to helping people nationwide live healthier lives by simplifying the health care experience, meeting consumer health and wellness needs, and sustaining trusted relationships with care providers. The company offers the full spectrum of health benefit programs for individuals, employers and Medicare and Medicaid beneficiaries, and contracts directly with more than 650,000 physicians and care professionals and 5,000 hospitals nationwide. UnitedHealthcare serves more than 38 million people and is one of the businesses of UnitedHealth Group, a diversified Fortune 50 health and well-being company.

SOURCE: UnitedHealthcare

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Updated AASLD HCV Guideline Aims To Simplify Use of DAAs

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Gastroenterology & Endoscopy News

ISSUE: APRIL 2012 | VOLUME: 63:4

by Christina Frangou

The American Association for the Study of Liver Diseases (AASLD) recently published an updated practice guideline on the treatment of chronic infection with hepatitis C virus (HCV) genotype 1 (Ghany MG et al. Hepatology 2011;54:1433-1444).

The guideline, authored by members of the AASLD practice guideline committee, was issued in response to the development of new direct-acting antivirals (DAAs) and the identification of several single nucleotide polymorphisms associated with spontaneous and treatment-induced clearance of HCV infection. The report makes 18 recommendations for clinicians who are considering using the new DAAs to treat patients with HCV. The two currently approved DAAs have complex prescribing rules, including outlines for response-guided therapy and unusual stopping rules, and many clinicians question how and when the agents are best used.

“We have entered into a very different treatment paradigm. I’d suggest that everyone read the guideline from the AASLD. It’s a very good overview of where we are today,” said David R. Nelson, MD, a study author and professor of medicine, Division of Gastroenterology, Hepatology and Nutrition at the University of Florida College of Medicine, in Jacksonville, during a presentation at The Liver Meeting last year.

The authors outline the current state of evidence regarding treatment with boceprevir and telaprevir, and provide some guidance on much-debated issues such as treatment of patients with cirrhosis and the role of interleukin-28B (IL28B) testing.

The guidelines are “very important and very helpful,” said Michal R. Charlton, MD, professor of medicine and head of the hepatobiliary section at Mayo Clinic, in Rochester, Minn. “The guidelines provide a lens through which clinicians can look to see the optimal approach to managing patients with HCV infection.”

Inside the Recommendations

According to the authors of the report, the DAAs, in combination with peginterferon alfa and ribavirin, are now the “optimal therapy” for treating HCV genotype 1 chronic infection. Both therapies must be given with peginterferon and ribavirin, which limits selection of resistant variants and improves antiviral response. Furthermore, boceprevir and telaprevir should not be used to treat patients infected with HCV genotype 2 or 3.

The authors reiterated the FDA recommendation that treatment-naive patients with cirrhosis treated with either boceprevir or telaprevir in combination with interferon and ribavirin should receive therapy for 48 weeks instead of on a response-guided basis. However, the authors added that this recommendation is “based on limited data and requires further study.”

The report also specifies that the stopping rules differ for telaprevir and boceprevir in treatment-naive patients. Treatment with telaprevir, peginterferon alfa and ribavirin should be stopped if the HCV RNA level is greater than 1,000 IU/mL at treatment weeks 4 or 12 and/or detectable at treatment week 24. Treatment with boceprevir, peginterferon and ribavirin should be stopped if the HCV RNA level is greater than 100 IU/mL at treatment week 12 or detectable at treatment week 24. For both therapies, the evidence for the discontinuation rules is considered Class 2a, meaning the weight of evidence is in favor of the usefulness of this rule, but there is limited evidence.

Patients who previously received and failed therapy with interferon and ribavirin remain a conundrum with regard to starting DAA therapy. Studies have shown that patients’ response to triple therapy regimens in both boceprevir and telaprevir trials was strongly influenced by the outcome of their earlier treatment with peginterferon and ribavirin. The decision to re-treat patients should depend on their previous response to peginterferon and ribavirin and on reasons why they may have failed, such as inadequate drug dosing or side-effect management, the report said. The authors call on physicians to review old treatment records to document previous treatment response.

This updated document is the first to clarify treatment for patients who fail DAA therapy. The authors say that patients who do not have a virologic response, who experience virologic breakthrough or who relapse on one protease inhibitor (PI) should not be retreated with the other PI.

Although the evidence is limited, the AASLD did make some recommendations for managing treatment-experienced patients. The AASLD suggests retreatment with boceprevir or telaprevir, together with peginterferon alfa and weight-based ribavirin, “be considered” for patients who had a virologic relapse or who were partial responders after a previous course of treatment with standard interferon alfa or peginterferon alfa and/or ribavirin.

“Relapsers and partial responder patients can expect relatively high sustained virologic response rates to retreatment with a PI-containing triple regimen and should be considered candidates for retreatment,” the authors wrote.

For previously null responders, telaprevir may be considered but boceprevir cannot be recommended, the committee found. This finding differs from the FDA label, which indicates that boceprevir can be used in null responders. Null responders were excluded from Phase III trials of boceprevir (Poordad F et al. N Engl J Med 2011;364:1195-1206).

“Given the lack of definitive information for Phase III data, caution is advised in the use of [boceprevir] in null responders until further supportive evidence becomes available,” according to the AASLD.

Additionally, the decision to re-treat a null responder with telaprevir should be individualized, particularly in patients with cirrhosis, because less than one-third of null responder patients in the telaprevir trial achieved a sustained virologic response (SVR). Moreover, the authors caution that a majority of null responders developed resistance to DAAs.

“Any potential benefit from treating nonresponders must be weighed against the risk for development of antiviral resistance and for serious side effects, and the high cost of therapy,” the report said.

The AASLD acknowledged uncertainty about the benefit of the lead-in strategy required for treatment with boceprevir. Theoretically, the lead-in may improve efficacy by lowering HCV RNA levels, thus reducing the rate of viral breakthrough when the PI is introduced. The authors noted, however, that poor responders during the lead-in period can still achieve SVR.

“Thus, a poor response during the lead-in phase should not be used to deny patients access to PI therapy,” the authors said. Patients who develop anemia on PI therapy should be managed by reducing the ribavirin dose, they added.

The report also specified that IL28B genotype is a significant treatment predictor of response to therapy, but data are insufficient to determine whether IL28B testing can be used to recommend either interferon and ribavirin alone or a triple therapy with a PI.

“Consideration should be given to ordering the test when it is likely to influence either the physician’s or patient’s decision to initiate therapy,” the authors said.

Telaprevir and boceprevir are not recommended for use in children and adolescents younger than 18 years because safety and efficacy has not been established in this group.

Additionally, the guidelines do not address several important questions about DAAs, Dr. Charlton said. The report, for example, does not provide detailed and practical information about drug–drug interactions, managing HIV/HCV co-infection and managing side effects, he said.

“Perhaps the highest-impact omission, which was unavoidable, is whether in light of the spectacular report of efficacy and tolerability of PSI-7977 in combination with ribavirin without interferon, patients with early stages of liver disease should be treated at all with boceprevir or telaprevir,” he said. “In our practice, we are already beginning to advise many patients to wait. … A strong case could be made for waiting for the results of the Phase III interferon-free studies.”

The committee cautions that the guidelines are “based on data that are presently limited” and the recommendations may need revision as additional data become available.

“There is a paucity of information for many of the subgroups with the greatest unmet need for treatment (e.g., patients co-infected with HIV and HCV, with decompensated cirrhosis and after liver transplantation),” the committee said.

Dr. Nelson receives research support from Bayer/Onyx, Bristol-Myers Squibb, Genentech/Roche, Gilead, Merck, Pharmasset, Tibotec and Vertex Pharmaceuticals; he serves on the advisory boards of Bayer/Onyx, Genentech/Roche, Gilead, Merck, Pharmasset and Tibotec; and he is a consultant for Vertex Pharmaceuticals. Dr. Charlton receives research support from Bristol-Myers Squibb, Genentech/Roche, Merck and Vertex Pharmaceuticals; he is a consultant for Bristol-Myers Squibb, Genentech/Roche Gilead, Merck and Vertex Pharmaceuticals.

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Statin Labels Updated

Gastroenterology & Endoscopy News

ISSUE: APRIL 2012 | VOLUME: 63:4

HCV Protease Inhibitor Contraindication Highlighted

by George Ochoa

The product labels on statins are changing to reflect new information deemed important by the FDA. The FDA announced the changes in late February as part of an overhaul of statin prescribing information.

One of the changes regards interactions between certain statins and hepatitis C virus (HCV) and HIV protease inhibitors. Taken together, statins and protease inhibitors may raise the blood levels of statins and increase the risk for muscle injury. One statin in particular, lovastatin, has been updated with new contraindications and dose limitations when it is taken with certain other drugs that can increase the risk for myopathy and rhabdomyolysis, including the HCV protease inhibitors boceprevir and telaprevir.

The FDA also approved labeling changes regarding the potential for statins to increase levels of blood sugar and glycosylated hemoglobin, signs of incipient type 2 diabetes. This decision was based on accumulating studies linking statins with the development of type 2 diabetes, the agency said. These included the Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin trial, which reported a 27% increase in investigator-reported diabetes in patients who received rosuvastatin compared with those who took a placebo (Ridker PM et al. N Engl J Med 2008;359:2195-2207); the Pravastatin or Atorvastatin Evaluation and Infection Therapy—Thrombolysis In Myocardial Infarction 22 substudy, which found an association between high-dose atorvastatin and worsening glycemic control (Sabatine MS et al. Circulation 2004;110:S834); and meta-analyses such as one by Sattar et al (Lancet 2010;375:735-742), which found that statin therapy was associated with a 9% increased risk for incident diabetes.

The potential for cognitive side effects, such as memory loss and confusion, in patients taking statins also was noted by the FDA. These side effects are generally reversible and not serious. The FDA stressed that “the cardiovascular benefits of statins outweigh these small increased risks.”

Additionally, statin labels have been revised to eliminate the need for routine periodic monitoring of liver enzymes in patients taking these drugs. Instead, statin labels now recommend the use of liver enzyme tests before starting the drugs and as clinically indicated afterward. Serious liver injury with statins is rare and unpredictable, according to the FDA, and routine periodic monitoring does not seem effective in detecting or preventing the problem.

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Gastroenterology & Endoscopy News

ISSUE: APRIL 2012 | VOLUME: 63:4

by George Ochoa

A February safety alert from the FDA warned that drug interactions between the hepatitis C virus (HCV) protease inhibitor (PI) boceprevir (Victrelis, Merck & Co., Inc.) and certain ritonavir-boosted HIV PIs may reduce the effectiveness of these medications when used together. The HIV PIs specified are atazanavir (Reyataz, Bristol-Myers Squibb), lopinavir (Kaletra, Abbott Laboratories) and darunavir (Prezista, Janssen Therapeutics). According to the FDA, a drug interaction study showed that taking boceprevir in combination with one of these drugs reduced blood levels of the HIV medications and boceprevir in the body.

The boceprevir label will be updated to reflect these drug interactions. Another HCV PI, telaprevir (Incivek, Vertex Pharmaceuticals Inc.), already carries warnings about drug interactions with HIV PIs.

“There has been considerable concern about the off-label use of these drugs and how they are used in patients with retroviral infections,” said Andrew Talal, MD, MPH, associate professor of medicine and associate medical director, Center for the Study of Hepatitis C, Weill Cornell Medical College, New York City. “I am pleased by the release of these data.”

Data presented on March 6 at the 19th Conference on Retroviruses and Opportunistic Infections (CROI) from researchers at Merck (Hulskotte E et al, paper 771LB) support the FDA action. Investigators evaluated drug interactions between boceprevir and ritonavir-boosted HIV PIs in 39 healthy adults. Blood samples were analyzed for pharmacokinetic characteristics of HIV PIs, ritonavir and boceprevir. The researchers found that boceprevir in combination with ritonavir-boosted atazanavir, darunavir and lopinavir resulted in reduced steady-state exposures of the HIV medications. Darunavir and lopinavir, but not atazanavir, lowered boceprevir exposure.

However, another study, presented on the same day at CROI (Sulkowski M et al, oral abstract Q-175), came to a different conclusion. This study evaluated the efficacy of boceprevir in patients co-infected with HIV and HCV genotype 1 who were previously untreated for HCV. Patients were treated with HIV PIs and also received boceprevir in combination with peginterferon alfa-2b/ribavirin (B/PR; n=64) or peginterferon alfa-2b/ribavirin (PR; n=34) alone. In an interim analysis, sustained virologic response at week 12 was achieved in 61% of patients in the B/PR group compared with 27% of patients in the PR group. The rates of HIV breakthrough (defined as HIV RNA >50 copies/mL at two consecutive visits) were 4.7% (three of 64) for patients who received boceprevir and 11.8% (four of 34) for those who did not.

“Although this study included a small number of patients, it did not demonstrate an increased rate of HIV breakthrough in patients receiving boceprevir plus HIV protease inhibitors compared with subjects receiving protease inhibitors alone,” said Kristen Marks, MD, assistant professor of medicine, Division of Infectious Diseases, Weill Cornell Medical College, New York City, and investigator, Cornell Clinical Trials, who was not involved in the study. “However, further study is needed to determine if HCV and HIV protease inhibitors can be safely used together.”

Dr. Talal said he would hold off initiating combination therapy with boceprevir and ritonavir-boosted HIV PIs in a patient with HCV–HIV co-infection who had not already been started on such therapy. As for patients who have already been started on the combination, the FDA alert recommends they should be closely monitored for HCV treatment response and potential HCV and HIV virologic rebound.

Dr. Marks said that she would make decisions about whether to continue treatment with boceprevir and a ritonavir-boosted HIV PI on a case-by-case basis.

“For example, if a patient has been on combination therapy for half a year and is doing well with respect to both HIV and HCV, I would leave them on it,” she said.

Dr. Talal has received research and consulting fees from Merck. Dr. Marks reported no relevant conflicts of interest.

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Gastroenterology & Endoscopy News

ISSUE: APRIL 2012 | VOLUME: 63:4

Results Based on Cost-Effectiveness Model

by Christina Frangou

San Francisco—For patients with hepatitis C virus (HCV) genotype 1 infection and the favorable CC interleukin-28B (IL28B) polymorphism, the clinical benefits of telaprevir do not outweigh the costs, according to the results of a cost-effectiveness model reported at The Liver Meeting 2011 (abstract 118).

“Under current cost and efficacy conditions, a telaprevir-based regimen is not cost-effective as a front-line treatment for these patients,” said lead author Ziad Gellad, MD, MPH, assistant professor of medicine, Duke Clinical Research Institute, Durham, N.C.

The price of HCV therapy has risen since the introduction of direct-acting antiviral drugs (DAAs) to the market. For example, a 12-week course of telaprevir combined with 36 weeks of pegylated interferon (Peg-IFN) and ribavirin is estimated to cost $85,872, and a full 48-week course of boceprevir-based therapy costs about $71,873. In contrast, the previous standard therapy without DAAs—48 weeks of Peg-IFN alfa and ribavirin—is approximately $36,672.

“Given the significant cost and potential side effects of telaprevir and boceprevir, it is important to ask whether all patients should be offered these agents as first-line therapies,” said George Makar, MD, assistant professor of clinical medicine and associate medical director of the liver transplant program, University of Pennsylvania, Philadelphia, who was not involved in the study.

Dr. Gellad and his team performed a cost-effectiveness comparison of three treatment strategies for HCV genotype 1 patients with the IL28B CC genotype, which is the strongest pretreatment predictor of sustained virologic response (SVR). The investigators included three treatment strategies in their model:

  • Peg-IFN alfa and ribavirin for 48 weeks, with a 12-week stopping rule for nonresponse and retreatment with telaprevir for nonresponders and relapsers;
  • A response-guided treatment strategy of Peg-IFN and ribavirin with treatment of 24 or 48 weeks based on rapid virologic response and retreatment with telaprevir for nonresponders and relapsers;
  • A response-guided treatment strategy of 12 weeks of telaprevir with 24 or 48 weeks of Peg-IFN and ribavirin.

Treatment outcomes were based on data from the IDEAL (The Individualized Dosing Efficacy vs. Flat Dosing to Assess Optimal Pegylated Interferon Therapy), REALIZE (Re-treatment of Patients with Telaprevir-based Regimen to Optimize Outcomes) and ADVANCE (A New Direction in HCV Care: A Study of Treatment-Naive Hepatitis C Patients with Telaprevir) clinical trials.

The model showed that the efficacy of all three treatment strategies was similar in this group of patients. Quality-adjusted life-years for the three treatments ranged from 19.26 to 19.34 years.

However, costs differed markedly. The total cost associated with a response-guided Peg-IFN and ribavirin regimen amounted to $46,785, by far the lowest, according to the model. The Peg-IFN/ribavirin regimen for 48 weeks with telaprevir as a retreatment strategy was $54,931. Telaprevir as a front-line therapy amounted to $68,788.

“Telaprevir was less likely than peginterferon/ribavirin to be cost-effective across all willingness-to-pay thresholds,” said Dr. Gellad.

Dr. Gellad said the analysis was not meant to guide treatment decisions at the patient level. “Rather, it was designed to address a policy question at the societal level. … Nonetheless, I hope it does raise some awareness about the judicious use of new and expensive therapies.”

One-way sensitivity analyses revealed that telaprevir became the preferred strategy in a number of scenarios: when the cost of telaprevir fell to less than $1,640 per week, when the likelihood of SVR in patients with nonextended rapid viral response rose greater than 80% and when the likelihood of SVR in relapsers retreated with telaprevir fell to less than 62%.

In Dr. Makar’s practice, he offers telaprevir and boceprevir to patients with a CC genotype who do not achieve a SVR with four weeks of Peg-IFN and ribavirin alone.

In patients with the IL28B CC genotype, the standard treatment is often successful, with SVR rates around 70% to 80% (Thompson AJ et al. Gastroenterology 2010;139:120-129). DAAs, however, are superior for patients who are nonresponsive or who relapse after dual therapy.

Dr. Makar said the cost-effectiveness analyses in the study will have to be reviewed closely.

“The potential for increased cost and side effects has to be weighted against the higher likelihood of SVR, as well as the much greater potential for shortened therapy,” he said, adding that patients also have to be actively involved in decision making.

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