AASLD: For HCV with Certain Genotypes, Peg-Interferon Alpha2a Edges Alpha2b

[Guest guest]

http://www.medpagetoday.com/MeetingCoverage/AASLD/11640

Medical News from

AASLD: American Association for the Study of Liver Diseases Meeting

AASLD: For HCV with Certain Genotypes, Peg-Interferon Alpha2a Edges Alpha2b

By , North American Correspondent, MedPage Today

Published: November 05, 2008

Reviewed by Zalman S. Agus, MD; Emeritus Professor

University of Pennsylvania School of Medicine. Earn CME/CE credit

for reading medical news

SAN FRANCISCO, Nov. 5 -- Pegylated interferon alpha2a is more effective in some

hepatitis C patients with specific genotypes than the alpha2b form of the drug,

an Italian researcher said here. Action Points

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

Explain to interested patients that two forms of pegylated interferon are used

to treat hepatitis C patients and it's not known if they have the same efficacy

and safety profiles.

Note that this study found an efficacy advantage for the alpha2a form of the

drug with patients with certain genotypes.

Note that this study was published as an abstract and presented orally at a

conference. These data and conclusions should be considered to be preliminary

until published in a peer-reviewed journal.

Pegylated interferon plus ribavirin is the standard of care for HCV, but the two

versions of the interferon have substantial differences, noted Grazia

Rumi, M.D., of Maggiore Hospital at the University of Milan.

The differences are in size, structure of the molecules, pharmacokinetics, and

biologic activity, and it had not been known whether they have the same efficacy

and safety profiles, she told the American Association for the Study of Liver

Diseases meeting.

To find out, she and colleagues conducted the randomized open-label Milan Safety

Tolerability (MIST) study from September 2003 through March 2007. They

randomized 212 patients to the alpha2a form and 219 to the alpha2b form. They

were stratified by genotype, and got fixed doses of ribavirin and alpha2a

interferon, but weight-based doses of the alpha2b form for 48 weeks.

The efficacy endpoint was sustained virological response six months after the

end of treatment, she said.

There were no significant differences in hematological disorders or common

adverse events between the two arms of the study, Dr. Rumi said.

On the other hand, the alpha2a form showed a clear advantage in efficacy:

Six months after treatment ended, 66% of patients getting the apha2a form had a

sustained virological response, compared with 54% for alpha2b, which was

significant at P=0.02.

At end of treatment, 78% of the alpha2a patients had responded, compared with

67% of the others, which was significant at P=0.009.

And 80% of the alpha2a patients had an early virological response, compared with

69%, which was significant at P=0.01.

There was no difference in rapid virological response.

When the researchers broke out the genotypes separately, they found significant

benefits of the alpha2a form for patients with genotypes one and two, but not

for three and four, she said.

The bottom line, Dr. Rumi said, is that at her institution, patients with

genotypes one and two are now treated only with the alpha2a form of the

interferon.

The researchers are planning larger trials to see whether they can improve

outcomes for patients with the other two genotypes, she said.

U.S. clinical trials have consistently shown the drugs to be equivalent and Dr.

Rumi's results may be partly explained by differences in study populations,

according to Tarek Hassanein, M.D., of the University of California at San

Diego, who was not involved in the study but moderated the session at which it

was presented.

He noted that the average body weight of volunteers in the study was about 70 kg

and their average body mass index was about 26.

" This is not what we see in the U.S., where the weight (in clinical trials) was

80 to 85 kg and the BMI was about 30, " he said. " These are totally different

types of populations. "

He added that about the midpoint of the study, clinicians began widely using

weight-based dosing to administer ribavirin. He said he would be interested to

see whether the results changed before and after that point.

Co-moderator Reem Ghalib, M.D., of Methodist Health System in Dallas, said it

may be too early to throw out the alpha2b form of the compound.

" We really need to see the final paper before making any conclusions, " she said.

Dr. Ghalib noted that " all the clinical trials in this country have shown them

to be equivalent " and in her clinical practice she makes no distinction -- " not

yet. "

Dr. Rumi did not report any external support for the study and said she had no

financial conflicts.

Primary source: Hepatology

Source reference:

Rumi M, et al " Randomized study comparing Peginterferon-alfa2a plus Ribavirin

and Peginterferon-alfa2b plus Ribavirin in naïve patients with chronic hepatitis

C: final results of the Milan Safety Tolerability (MIST) study " Hepatology 2008;

48(4): Abstract 212.

[Guest guest]

http://www.medpagetoday.com/MeetingCoverage/AASLD/11640

Medical News from

AASLD: American Association for the Study of Liver Diseases Meeting

AASLD: For HCV with Certain Genotypes, Peg-Interferon Alpha2a Edges Alpha2b

By , North American Correspondent, MedPage Today

Published: November 05, 2008

Reviewed by Zalman S. Agus, MD; Emeritus Professor

University of Pennsylvania School of Medicine. Earn CME/CE credit

for reading medical news

SAN FRANCISCO, Nov. 5 -- Pegylated interferon alpha2a is more effective in some

hepatitis C patients with specific genotypes than the alpha2b form of the drug,

an Italian researcher said here. Action Points

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

Explain to interested patients that two forms of pegylated interferon are used

to treat hepatitis C patients and it's not known if they have the same efficacy

and safety profiles.

Note that this study found an efficacy advantage for the alpha2a form of the

drug with patients with certain genotypes.

Note that this study was published as an abstract and presented orally at a

conference. These data and conclusions should be considered to be preliminary

until published in a peer-reviewed journal.

Pegylated interferon plus ribavirin is the standard of care for HCV, but the two

versions of the interferon have substantial differences, noted Grazia

Rumi, M.D., of Maggiore Hospital at the University of Milan.

The differences are in size, structure of the molecules, pharmacokinetics, and

biologic activity, and it had not been known whether they have the same efficacy

and safety profiles, she told the American Association for the Study of Liver

Diseases meeting.

To find out, she and colleagues conducted the randomized open-label Milan Safety

Tolerability (MIST) study from September 2003 through March 2007. They

randomized 212 patients to the alpha2a form and 219 to the alpha2b form. They

were stratified by genotype, and got fixed doses of ribavirin and alpha2a

interferon, but weight-based doses of the alpha2b form for 48 weeks.

The efficacy endpoint was sustained virological response six months after the

end of treatment, she said.

There were no significant differences in hematological disorders or common

adverse events between the two arms of the study, Dr. Rumi said.

On the other hand, the alpha2a form showed a clear advantage in efficacy:

Six months after treatment ended, 66% of patients getting the apha2a form had a

sustained virological response, compared with 54% for alpha2b, which was

significant at P=0.02.

At end of treatment, 78% of the alpha2a patients had responded, compared with

67% of the others, which was significant at P=0.009.

And 80% of the alpha2a patients had an early virological response, compared with

69%, which was significant at P=0.01.

There was no difference in rapid virological response.

When the researchers broke out the genotypes separately, they found significant

benefits of the alpha2a form for patients with genotypes one and two, but not

for three and four, she said.

The bottom line, Dr. Rumi said, is that at her institution, patients with

genotypes one and two are now treated only with the alpha2a form of the

interferon.

The researchers are planning larger trials to see whether they can improve

outcomes for patients with the other two genotypes, she said.

U.S. clinical trials have consistently shown the drugs to be equivalent and Dr.

Rumi's results may be partly explained by differences in study populations,

according to Tarek Hassanein, M.D., of the University of California at San

Diego, who was not involved in the study but moderated the session at which it

was presented.

He noted that the average body weight of volunteers in the study was about 70 kg

and their average body mass index was about 26.

" This is not what we see in the U.S., where the weight (in clinical trials) was

80 to 85 kg and the BMI was about 30, " he said. " These are totally different

types of populations. "

He added that about the midpoint of the study, clinicians began widely using

weight-based dosing to administer ribavirin. He said he would be interested to

see whether the results changed before and after that point.

Co-moderator Reem Ghalib, M.D., of Methodist Health System in Dallas, said it

may be too early to throw out the alpha2b form of the compound.

" We really need to see the final paper before making any conclusions, " she said.

Dr. Ghalib noted that " all the clinical trials in this country have shown them

to be equivalent " and in her clinical practice she makes no distinction -- " not

yet. "

Dr. Rumi did not report any external support for the study and said she had no

financial conflicts.

Primary source: Hepatology

Source reference:

Rumi M, et al " Randomized study comparing Peginterferon-alfa2a plus Ribavirin

and Peginterferon-alfa2b plus Ribavirin in naïve patients with chronic hepatitis

C: final results of the Milan Safety Tolerability (MIST) study " Hepatology 2008;

48(4): Abstract 212.