$1,000-a-pill Sovaldi jolts US health care system (Update)

This undated handout photo provided by Gilead Sciences shows the Hepatitis-C medication Sovaldi. Sovaldi, a new pill for hepatitis C, cures the liver-wasting disease in 9 of 10 patients, but treatment can cost more than $90,000. Leading medical societies recommend the drug and patients are clamoring for it. But insurance companies and state Medicaid programs are gagging on the price. In Oregon, officials propose to limit how many low-income patients can get it. (AP Photo/Gilead Sciences)

17 jun 2014--The latest pill for hepatitis C sounds like a difficult choice. Sovaldi cures the liver-wasting disease in 9 of 10 patients, but treatment can cost more than $90,000.

Leading medical societies recommend the drug as a first-line treatment, and patients are clamoring for it. But insurance companies and state Medicaid programs are gagging on the price. In Oregon, officials propose to limit how many low-income patients can get Sovaldi.

Yet if Sovaldi didn't exist, insurers would still be paying in the mid-to-high five figures to treat the most common kind of hepatitis C, a new pricing survey indicates. Some of the older alternatives involve more side effects, and are less likely to provide cures.

So what's a fair price?

The cost of this breakthrough drug is highlighting cracks in the U.S. health care system at a time of heightened budget concerns. The Obama administration has a huge political stake in controlling treatment costs, but its critics may cry rationing.

"People are going to want to try to dodge this hot potato," says economist Douglas Holtz-Eakin.

For insurers, there's a frustrating twist: For each middle-aged person they pay to cure with Sovaldi, any financial benefits from preventing liver failure are likely to accrue to Medicare, not to them.

More than 3 million Americans carry the hepatitis C virus, and many don't realize it. It's a public health concern since the disease can be transmitted by contact with infected blood, and sometimes through sexual activity. Health officials advise all baby boomers to get tested.

This undated handout photo provided by Gilead Sciences shows the Hepatitis-C medication Sovaldi. Sovaldi, a new pill for hepatitis C, cures the liver-wasting disease in 9 of 10 patients, but treatment can cost more than $90,000. Leading medical societies recommend the drug and patients are clamoring for it. But insurance companies and state Medicaid programs are gagging on the price. In Oregon, officials propose to limit how many low-income patients can get it. (AP Photo/Gilead Sciences)

The illness is complex, with distinct virus types requiring different treatments. While it progresses gradually, it can ultimately destroy the liver, and transplants average $577,000.

An estimated 15,000 people died from hepatitis C in the U.S. in 2007, when it surpassed AIDS as a cause of death.

"If it's going to get me the medicine, I'll put my hand out there with a tin cup," said Stuart Rose, a hepatitis C patient in New York City. His insurance would pay only $4,000 a year for medications, but Rose was able to get assistance from charitable foundations. He recently started taking Sovaldi.

Until the drug's approval late last year, standard treatment for the most common type of the disease required daily pills and extended use of interferon, an injection that can produce debilitating flu-like symptoms. "Brain fog," said Rose.

Taken once a day for 12 weeks, Sovaldi greatly reduces the length of interferon treatment, making things more tolerable for patients. Now, many more people might want to try the cure.

A similar drug, Olysio, also approved last year, is priced a bit lower.

The nation's largest care provider for chronic hepatitis C, the federal Veterans Administration, sees promise. With 175,000 patients, the VA has started more than 1,850 of them on Sovaldi.

"After 20 years in infectious diseases, I never thought we would be in a position to cure this disease," said Dr. David Ross, head of the VA's program.

By law, the VA gets drug discounts of over 40 percent. Will the agency break even by avoiding the disease's worst complications?

Not necessarily, said Ross. "If it leads to cost benefits in the long run, that's gravy."

Private insurers will probably introduce Sovaldi gradually. "Not everybody is going to get this all at once," said former Medicare administrator Mark McClellan.

Drug maker Gilead Sciences, Inc., reported Sovaldi sales of $2.3 billion worldwide in just the first three months of this year. Gilead will not disclose its pricing methods, but vice president Gregg Alton said the drug's high cure rate makes it "a real huge value."

In many countries, the government sets drug prices. In the US, insurers negotiate with drug companies. Medicare, the government health program for the elderly, is forbidden from bargaining, a situation that critics say saddles U.S. patients with high costs while subsidizing the rest of the world.

Screen all baby boomers for hepatitis C, expert panel says

This generation has highest rate of infection, likely contracted decades ago.

This generation has highest rate of infection, likely contracted decades ago.

27 jun 2013—All adults born between 1945 and 1965—the baby boom generation—should be screened for the hepatitis C virus along with injection-drug users and anyone transfused before 1992, according to new recommendations from the U.S. Preventive Services Task Force.

The guidelines, released Monday, mirror recommendations from the U.S. Centers for Disease Control and Prevention and provide a long-awaited policy from the task force, an independent panel of experts.

"For everyone born between 1945 and 1965 we recommend a one-time screening," said task force member Dr. Kirsten Bibbins-Domingo, an associate professor in residence at the University of California, San Francisco, School of Medicine.

People in this age group account for three-quarters of all hepatitis C cases in the United States, Bibbins-Domingo said. Many contracted the disease decades ago but don't know it.

Hepatitis C—a leading cause of liver damage and liver disease in the United States—is considered a silent killer because it progresses without any indications of illness. More than 30 percent of U.S. patients needing liver transplants have end-stage liver disease related to hepatitis C.

"The challenge is that many people have hepatitis C and don't have signs and symptoms of the disease," Bibbins-Domingo said. "Those people should be identified and consider treatment."

An estimated 3.9 million people are infected with hepatitis C in the United States, the task force said. Unlike other types of hepatitis, there is no vaccine for hepatitis C.

In its 2004 statement, the task force advised against routine screening of adults without symptoms and high risk of infection. It also said it had too little evidence to recommend for or against routine screening for adults with high risk of infection.

It became apparent, however, that two-thirds of infected people weren't getting screened, while treatment was becoming more successful.

"Many people appear to benefit from treatment," Bibbins-Domingo said. "That is what led the task force to conclude that it is beneficial for people to find out they have hepatitis C in order to seek treatment."

Dr. Marc Siegel, an associate professor of medicine at NYU Langone Medical Center in New York City, said he welcomes the new guidelines, which were published June 25 in the Annals of Internal Medicine.

"I am absolutely thrilled that the U.S. Preventive Services Task Force, which has had a head-in-the-sand approach toward screening, has come out for a one-time screening for hepatitis C," Siegel said.

Siegel encourages everyone at risk to get tested.

Screening for hepatitis C involves a simple, inexpensive blood test. Those who test positive usually receive a course of antiviral medication over several months. Most people have no detectable virus following treatment, Bibbins-Domingo said.

"Treatment is effective in preventing the complications of hepatitis C," Bibbins-Domingo said. "Treatments have gotten better, and I suspect treatments will continue to get better."

Many people who test positive for the virus have no signs of active infection. Whether they should be treated should be discussed with their doctor, she said.

Although baby boomers should have a one-time screening, those who continue to be at risk for the infection should be screened more often, Bibbins-Domingo said.

Past or current injection-drug use is the greatest risk for hepatitis C infection. Also at high risk are people with a history of blood transfusions before widespread adoption of screening and infection-control measures in 1992; people who have undergone long-term dialysis treatment; and those with exposure to hepatitis C in health care settings. People with HIV/AIDS, a history of intranasal drug use or tattoos from unregulated or unsafe parlors also are at greater risk than the general population.

This expanded screening may identify millions of Americans who were unaware of their infection, the task force said.

U.S. task force: Baby boomers should be tested for hepatitis C

Generation has highest rate of infection, likely contracted decades ago.

27 nov  2012—A U.S. task force suggests that people at high risk for the hepatitis C virus should be screened, which includes those with a history of intravenous drug use and those who received blood transfusions before 1992.

But, the guidelines also address another, lower-risk group—the baby boomer generation.

The new U.S. Preventive Services Task Force guidelines, released Monday and updated from 2004, take a somewhat softer stance than those of the U.S. Centers for Disease Control and Prevention, which say that all baby boomers should get screened for hepatitis C. By contrast, the task force suggests that clinicians "consider" screening for this age group, which includes those born between 1946 and 1964.

Screening for hepatitis C involves a simple, inexpensive blood test. Unlike other types of hepatitis, there is no vaccine available for hepatitis C. Treatment typically involves a course of antiviral medication.

Hepatitis C is considered a silent killer because it is often symptomless. Undiagnosed and untreated, hepatitis C can result in liver cancer, liver failure and liver transplants.

Risk factors for hepatitis C infection include a history of blood transfusions before widespread adoption of screening and infection control measures, long-term dialysis treatment, exposure to hepatitis C in health care settings, having HIV/AIDS, tattooing in unregulated or unsafe parlors and IV drug use.

"Our recommendations are that people who are known to be at high risk—such as people with a history of IV drug [use] and those who had blood transfusions prior to 1992—should be screened," said task force member Dr. Kirsten Bibbins-Domingo, an associate professor of medicine and of epidemiology and biostatistics at the University of California, San Francisco.

People at highest risk have about a 50 percent chance of being infected with hepatitis C; whereas people born between 1946 and 1964 have a 3 percent to 4 percent chance of being infected, she said.

Bibbins-Domingo said the task force took less a stringent stance on testing for all baby boomers because many people with hepatitis C will live for a long time without progressive disease, and current treatments don't help everyone. "We have effective treatments, but not everybody who has hepatitis C will go on to develop liver failure or liver cancer," she said. "We are in an era where treatments are rapidly evolving, and recommendations may change as treatments get better."

One liver disease expert weighed in on screening for the 47-to-67 age group.

Dr. David Bernstein, chief of hepatology at North Shore-LIJ Healthcare System, in Manhasset, N.Y, said baby boomers should get screened for hepatitis C. "I think the guidelines should have been a little stronger for people born from 1945 to 1965," he said.

"The current therapies have cure rates of 70 to 75 percent," Bernstein said. "In a couple of years, newer therapies may be available which will have much higher cure rates but this is [already] very high."

Get screened, he advised. "Hepatitis C is the most common reason for a liver transplant and development of liver cancer, but if you catch it, you can halt the progression of disease and cure it."

The task force guidelines are now open for a period of public comment.

More information: Get the facts about hepatitis C at the U.S. National Library of Medicine.

Difficult-to-Treat Hepatitis C Patients Respond to Pegylated Interferon-Alpha/Ribavirin


ESSEN, Germany, Dec. 5 -- Pre-existing psychiatric comorbidities -- including depression and schizophrenia -- did not worsen when hepatitis C patients were treated with pegylated interferon-alpha and ribavirin.
Action Points --->
Explain to interested patients that this report suggests that patients with hepatitis C who have psychiatric comorbidities respond well to standard antiviral therapy.
Explain, too, that this study suggests that a special interdisciplinary approach that allows for close monitoring is important when treating patients who have both hepatitis C and psychiatric diagnoses.
Moreover, those comorbidities did not adversely affect sustained virological response to treatment, according to Martin Schaefer, M.D., of Essen Hospitals, and colleagues.
But the key to success in this difficult-to-treat population was a multidisciplinary approach in which hepatologists worked closely with psychiatrists, the researchers said. They strongly recommended "offering interdisciplinary treatment units in order to optimize adherence and response rates and to manage effects."
The study enrolled 70 patients with chronic hepatitis C infection; 22 of them had psychiatric disorders, 18 were on methadone maintenance, 13 were former drug users, and 17 were free of psychiatric or substance abuse diagnoses.
All patients received pegylated interferon-alpha subcutaneously (57 received 1.5 mg/kg per week and 13 received 180 mg/kg per week) plus ribavirin 800 to 1,200 mg/day orally according to body weight. Genotypes 2 and 3 received antiviral treatment for 24 weeks; genotypes 1 and 4 were treated for 48 weeks.
Depression was measured at baseline and during treatment using the Montgomery-Asberg Depression Rating Scale (MADRS), which defines mild depression as a score between 7 and 19, moderate depression as 20 to 33, and more than 33 as severe depressive syndrome.
Psychotic symptoms were evaluated with the Brief Psychiatric Rating Scale (BPRS) -- a 7-point severity scale that rates individual symptoms from 0 to 7, with 7 indicating extremely severe.
Sustained virological response was found in 58.6% of all patients, with the individual rates breaking down this way: 50% of psychiatric patients, 72.2% of those taking methadone, 53.8% of former drug users, and 58.8% of controls, according to findings published in the October issue of Hepatology.
Not surprisingly, the methadone patients and the former drug users had higher dropout rates -- 27.8% in the methadone group and 15.4% among former drug users versus 9.1% for psychiatric patients and 5.9% among controls. Of the 70 patients enrolled in the study, only ten dropped out.
During treatment, MADRS scores increased significantly for all patients, except those on methadone (P<0.001 compared with baseline for controls, P=0.006 for psychiatric patients, and P=0.039 for former drug users).
Methadone patients and former drug users had the highest BPRS scores at baseline and during treatment. However, only those in the control group had psychiatric changes during treatment that approached significance (P=0.055).
Dr. Schaefer said the study was limited by its small size and by the exclusion of homeless patients, those with dementia and other organic brain diseases, and those with ongoing drug or alcohol abuse.
Nonetheless, in an editorial that accompanied the study, Cynthia M.A. Geppert, M.D., Ph.D., M.P.H., and Sanjeev Arora, M.D., both of the University of New Mexico, said it was a pivotal study.
They wrote that close to 20% of patients with severe mental illness are believed to be HCV-positive, yet hepatologists have been reluctant to treat these patients because of concerns that interferon would exacerbate depression as well as anxiety, suicidality, mania, and psychosis.
The study by Schaefer et al, as the first prospective study in this population, supports the "development of evidence-based thinking regarding whether mental health disorders should continue to be considered as exclusions for therapy with pegylated interferon and ribavirin," Drs. Geppert and Arora wrote.
Dr. Schaeffer reported no potential conflicts of interest but a co-author disclosed that he is a consultant for Pfizer and AstraZeneca and received grants from Janssen-Cilag, Bristol-Myers Squibb, and Lilly. They did not disclose a funding source for the study.
Primary source: HepatologySource reference:Schaefer M, et al "Hepatitis C treatment in 'difficult-to-treat' psychiatric patients with pegylated interferon-alpha and ribavirin: response and psychiatric side effects" Hepatology 2007; 46: 991-998. Additional source: HepatologySource reference: Geppert C, Arora S, "Widening the door: the evolution of hepatitis C treatment in patients with psychiatric disorders" Hepatology 2007; 46: 957-959.

New Drug May Help Increase Platelet Counts in Patients With Hepatitis C

Laurie Barclay, MD

November 28, 2007 — Eltrombopag (Promacta, Revolade; GlaxoSmithKline) may help increase platelet counts in patients with hepatitis C virus (HCV) infection, thereby enabling them to take antiviral drugs, according to the results of a randomized controlled trial reported in the November 29 issue of the New England Journal of Medicine. This new, orally active thrombopoietin-receptor agonist also increased platelet counts in patients with idiopathic thrombocytopenic purpura.
"We feel this is an important development for many people infected with [HCV] worldwide," lead author John G. McHutchison, MD, from the Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, says in a news release. "A significant number of patients with HCV infection will at some point develop platelet problems that will compromise their getting the best treatments we have. Anything we can do to prevent that from happening would improve their care."
In this phase 2, multicenter trial, 74 patients with cirrhosis caused by HCV and with platelet counts between 20,000 and 70,000/mm3 were randomly assigned to receive either eltrombopag (30, 50, or 75 mg) or placebo daily for 4 weeks. The main efficacy outcome measure was a platelet count of 100,000/mm3 or more at week 4. Eltrombopag or placebo were continued for 12 additional weeks, and peginterferon and ribavirin could be started at week 4.
At week 4, platelet counts were increased to 100,000/mm3 or more in none of the 17 patients receiving placebo. However, in patients with available data, eltrombopag was associated with platelet increases in a dose-dependent manner. Platelet counts of 100,000/mm3 occurred in 9 (75%) of 12 patients receiving a 30-mg dose of eltrombopag daily, in 15 (79%) of 19 receiving a 50-mg dose, and in 20 (95%) of 21 receiving a 75-mg dose (P < .001).
During continued administration of eltrombopag or placebo, antiviral therapy was started in 49 patients, with 4 of 18 patients receiving placebo, 10 of 14 receiving 30 mg eltrombopag, 14 of 19 receiving 50 mg eltrombopag, and 21 of 23 receiving 75 mg eltrombopag. Twelve weeks of antiviral therapy were completed by 36%, 53%, and 65% of patients receiving 30, 50, and 75 mg of eltrombopag, respectively, and by 6% of patients in the placebo group, while administration of eltrombopag or placebo was ongoing.
"We are encouraged by these results and are already working on another multicenter, international, phase 3 trial where we hope these results will be confirmed," Dr. McHutchison said.
Headache was the most frequently reported adverse event during the first 4 weeks of the study. Other adverse effects were dry mouth, abdominal pain, and nausea. During the last 8 weeks of the study, reported adverse events were those typically associated with interferon-based therapy.
Study limitations were small sample size and insufficient power to determine whether adverse events were dose-related.
"Eltrombopag therapy increases platelet counts in patients with thrombocytopenia due to HCV-related cirrhosis, thereby permitting the initiation of antiviral therapy," the authors concluded. "These results require confirmation in phase 3 trials involving standard-duration courses of peginterferon and ribavirin."
GlaxoSmithKline supported this study, employs 4 of its authors, and has various financial arrangements with some other authors. Some of the authors report various financial arrangements with Roche and/or Schering-Plough.
N Engl J Med. 2007;357:2227–2236.

Weight-Based Dosing of Ribavirin and Pegylated Interferon Is Useful for Hepatitis C

October 5, 2007 — Weight-based dosing (WBD) of ribavirin in combination with pegylated interferon (PEG-IFN) is better than standard flat dosing (FD) for treating chronic hepatitis C (HCV), particularly in African-American patients with HCV genotype 1, according to 2 reports from the Weight-Based Dosing of Peginterferon alfa-2b and Ribavirin (WIN-R) trial published in the October issue of Hepatology.
"With pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy, more than 50% of patients with compensated liver disease from hepatitis C virus (HCV) infection attain sustained virologic response (SVR)," write Ira M. Jacobson, from the Medical College of Cornell University in New York, and colleagues from the WIN-R Study Group. "Several factors influence treatment response, including baseline viral load and HCV genotype; optimizing drug dosing and treatment duration is essential to maximizing response."
This prospective, open-label efficacy and safety trial took place at 236 US community and academic sites. Treatment-naive adult patients with chronic HCV and compensated liver disease (n = 5027) were randomized to receive PEG-IFN alfa-2b at 1.5 µg/kg/week plus FD (800 mg/day) or WBD (800 - 1400 µg/day) ribavirin for 48 weeks (patients with genotype 1, 4, 5, or 6) and for 24 or 48 weeks (patients with genotype 2 or 3). WBD ribavirin was 800 mg/day for weight less than 65 kg, 1000 mg/day for 65 to 85 kg, 1200 mg/day for more than 85 to 105 kg, or 1400 mg/day for more than 105 to less than 125 kg.
The main outcome measure was SVR, defined as undetectable (< 125 IU/mL) serum HCV RNA at 24-week follow-up in patients weighing more than 65 kg.
Compared with FD ribavirin, WBD ribavirin was associated with significantly higher SVR, but not end-of-treatment, rates (44.2% vs 40.5%; P = .008). Intent-to-treat analysis revealed SVR rates of 34.0% and 28.9%, respectively, in patients with genotype 1 (P = .005) and 31.2% and 26.7%, respectively, in patients with genotype 1 with a high baseline viral load (P = .056). Regardless of treatment duration, rates were not significantly different between groups of patients with genotypes 2 and 3 (61.8% and 59.5%, respectively).
Reductions in hemoglobin levels were greater with WBD ribavirin, but safety profiles were otherwise similar across ribavirin dosing groups, including the 1400-mg/day group.
"PEG-IFN alfa-2b plus weight-based RBV is more effective than flat-dose RBV, particularly in genotype 1 patients, providing equivalent efficacy across all weight groups," the study authors write. "RBV 1400 mg/day is appropriate for patients 105 to 125 kg. For genotype 2/3 patients, 24 weeks of treatment with flat-dose RBV is adequate; no evidence of additional benefit of extending treatment to 48 weeks was demonstrated."
Limitations of the study include inability to determine whether therapy duration could be shortened to less than 24 weeks based on viral clearance by week 4; inability to draw definitive conclusions about duration of therapy in selected subgroups of patients with genotypes 2 and 3, such as patients with advanced fibrosis or those with slow therapeutic response; restriction to US patients; and loss of patients to follow-up.
"The WIN-R trial shows both the power and the limitations of investigator-initiated trials to evaluate therapeutic issues for which very large populations are necessary," the study authors conclude. "This trial confirmed that WBD RBV is superior to FD RBV for patients with HCV G1 [genotype 1]; established the efficacy and safety of a new dosage of 1400 mg/day for patients who weigh >105 kg; demonstrated equivalent rates of SVR across a spectrum of body weights with WBD dosing of RBV and PEG-IFN alfa-2b; and showed, in a larger study population than hitherto reported, equivalent SVR rates between 24 and 48 weeks of treatment for patients with HCV G2 and G3."
Schering-Plough Corp. supported this study and employs 2 of its authors. Some of the other authors have disclosed various financial relationships with Schering-Plough, Merck, GlobeImmune, Human Genome Sciences, Coley, Gilead, Vertex, Intermune, Intarcia, Valeant, GlaxoSmithKline, Idenix, Novartis, Bristol-Myers Squibb, Boehringer Ingelheim, XTL, and Roche.
"Given the disproportionate prevalence of [chronic hepatitis C] in African American individuals and the lower rates of response to IFN-based therapy, it is important to evaluate ways of maximizing treatment response to HCV therapy," Dr. Jacobson and colleagues from the WIN-R Study Group write in the second report. "Tailoring therapy according to body weight may accomplish this, particularly in light of the finding that the prevalence of obesity is higher in African American persons, particularly women, than in other ethnic groups. The WIN-R study enrolled more than 400 African American patients, constituting the largest database available on treatment of African American individuals with HCV infection."
This subanalysis evaluated the efficacy of WBD among previously untreated African-American patients with genotype 1 infection who were enrolled in the WIN-R trial.
In the primary efficacy analysis, 188 of 362 African-American patients received ribavirin FD and 174 received WBD. Compared with the FD group, the WBD group had higher SVR rates (21% vs 10%; P = .0006) and lower relapse rates (22% vs 30%). Safety profiles and rates of drug discontinuation were similar in both groups.
"Weight-based dosing of RBV is more effective than flat dosing in combination with PEG-IFN alfa-2b in African American individuals with HCV genotype 1," the study authors write. "Even with weight-based dosing, response rates in African American individuals are lower than reported in other ethnic groups."
Limitations of the second study include a subanalysis that was not powered for statistical significance, high patient dropout rates and missing patient data, absence of rigorous compliance monitoring, lack of details concerning use of growth factor, difficulty extrapolating these findings to other relatively treatment-resistant populations, and incomplete data regarding use of erythropoietin.
"When combined with PEG-IFN alfa-2b, WBD RBV offers a significant advantage in efficacy, with acceptable tolerability, over FD of RBV in the treatment of African American patients infected with HCV G1," the study authors conclude. "However, even with WBD RBV, the rate of SVR in African American individuals is low. Studies designed to explain this phenomenon have been conducted, but further studies are needed to elucidate the fundamental basis for the impaired responsiveness in this population."
In an accompanying editorial, Jason Smith, PharmD, and Steven-Huy B. Han, MD, AGAF, from the Greater Los Angeles Veterans Healthcare Administration Hospital and David Geffen School of Medicine at the University of California Los Angeles, call these results "compelling" but recommend a large, prospective, randomized controlled trial.
"At least the traditional notion that ribavirin dosage should be fixed has now been sidelined by the idea that we should tailor ribavirin dosing to our patients," Drs. Smith and Han write. "Despite our lack of confidence in secondary analysis, important information can be derived from this African American substudy and future studies that are inspired by this trial. The WIN-R subanalysis of African American patients may not have the power to detect its statistical goal, but it does have the power to change the way we think about ribavirin dosing in African Americans, who will benefit from the awareness derived herein and its translation into more vigilant care of this difficult-to-treat population."
Hepatology. 2007;46:953-956, 971-981, 982-990.

Longer HCV Treatment Outperforms Short Course

RICHMOND, Va., July 11 -- Longer is better when it comes to treatment for hepatitis C, researchers here said.
In an industry-sponsored clinical trial, outcomes were significantly inferior when patients were treated with pegylated interferon alfa-2a (Pegasys) and ribavirin (Copegus) for 16 weeks instead of the standard 24, according to a report in the July 12 issue of the New England Journal of Medicine.
The finding supports current recommendations that patients with hepatitis C genotypes two or three should be treated for 24 weeks, said Mitchell Shiffman, M.D., of Virginia Commonwealth University Medical Center, and colleagues.
About 80% of patients with those genotypes who are treated for 24 weeks have a sustained virologic response - defined as less than 50 IU of hepatitis RNA per mL of serum 24 weeks after the end of treatment. (Patients with genotype one require 48 weeks of therapy.)
But small, randomized trials had suggested that shortening the treatment period could provide much the same benefit at lower cost and with fewer adverse events, the researchers noted. (See Short-Course Treatment Effective In Chronic HCV)
To help settle the issue, the researchers randomized 1,469 patients with hepatitis C genotypes two or three to receive 180 micrograms of peginterferon alfa-2a weekly and 800 milligrams of ribavirin daily for either 16 or 24 weeks.
The 16-week course of treatment was significantly inferior, the researchers found:
Sustained virologic response - the primary endpoint - was 62% in the 16-week group and 70% in the 24-week group.
The odds ratio for a sustained response was 0.67, with a 95% confidence interval from 0.54 to 0.84, which was significant at P<0.001.
The relapse rate - defined as detectable hepatitis RNA during follow-up in patients who had undetectable levels at the end of treatment -- was 31% in the 16-week group and 18% in the 24-week group, which was significant at P<0.001.
In patients with a low pre-treatment viral level (400,000 IU per milliliter or less), the sustained virologic response rate was 82% in the 16-week group and 81% in the 24-week group.
Among patients who responded quickly (with undetectable hepatitis by the fourth week) the sustained virologic response rates were 79% in the 16-week group and 85% in the 24-week group, a difference that was significant at P=0.02.
Interestingly, at the end of treatment, patients in the 16-week group were almost twice as likely as those in the other arm to have undetectable serum levels of hepatitis RNA, the researchers found, because more patients in the 24-week group withdrew early and were considered not to have had a response.
In other words, the difference in sustained virologic response is caused almost entirely by the increased relapse rate in the 16-week group, the researchers said.
Adverse events were similar between the arms, the researchers said.
Low initial viral load and rapid initial response predicted a better outcome, the researchers said, so shorter treatment duration might be possible in such patients.
In general, however, "these patients should not be routinely treated for less than the currently recommended 24 weeks," they concluded.
While the findings appear stark and clear, the take-home message may be "more complicated than the findings of the current study suggest," according to T. Jake Liang, M.D., of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md.
In fact, Dr. Liang said in an accompanying editorial, some of the detailed results of the study suggest a one-size-fits-all approach may be less effective than tailoring treatment to the individual.
For example, he said, the study's findings suggest that "patients with [hepatitis] genotype three, high viral load, advanced fibrosis, and obesity who are black, older, and male should be treated for 24 weeks."
In contrast, he said, whites with genotype two and the opposite characteristics could get a good outcome after 16 weeks.
As the state of knowledge increases, he said, it should be possible to construct "a customized management and therapeutic regimen" for each patient.
The study was supported by Roche. Dr. Shiffman reports financial links with Roche, Schering-Plough, Vertex Pharmaceuticals, Valeant, Coley Pharmaceuticals, Gilead Sciences, and GlaxoSmithKline. Other investigators report financial links with Roche, Schering-Plough, Coley Pharmaceuticals, Intermune, Valeant, Gilead, GlaxoSmithKline, and Human Genome Sciences. Two authors, Amy Lin, M.S., and Ash Soman, M.B.B.S, are employees of Roche. Primary source: New England Journal of MedicineSource reference: Shiffman ML et al. "Peginterferon Alfa-2a and Ribavirin for 16 or 24 Weeks in HCV Genotype 2 or 3." N Engl J Med 2007;357:124-34. Additional source: New England Journal of MedicineSource reference: T. Jake Liang "Shortened Therapy for Hepatitis C Virus Genotype 2 or 3 - Is Less More?" N Engl J Med 2007;357:176-78.