Pegylated + Ribavirin

[Guest guest]

Dear Florence,

Probably the only reason there were no 3's was because there were so

few people in this study, and there aren't as many people with genotype as 1

and 2. The odds were just against it! It's the same reason you hear mostly

about 1's and 2's. There are just more of us. It would have been nice to

see a larger study with the breakdown by genotype. In fact, there probably

is, if I run across it I'll post it.

Claudine

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[Guest guest]

Dear Florence,

Probably the only reason there were no 3's was because there were so

few people in this study, and there aren't as many people with genotype as 1

and 2. The odds were just against it! It's the same reason you hear mostly

about 1's and 2's. There are just more of us. It would have been nice to

see a larger study with the breakdown by genotype. In fact, there probably

is, if I run across it I'll post it.

Claudine

________________________________________________________________________

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[Guest guest]

Claudine,

Thank you very much for the info. I will look into Peg ,(if they apply it

to 3's), because if it works for 1's, I'm in. I wonder why they only

show results for 1's and 2's.....are they assuming 3 is an automatic or do

you have to be in a certain stage to be in a trial with 3? I still feel

lucky about my geno but lately I have been reading only about 1's and 2's.

I think I am missing something (besides some brain cells) as I am

ignorant on 'what' determines who gets treated. I signed up for a trial

here locally and all I am receiving from them is more questionaires with

different questions. I would prefer the trial because they are very savvy

on treatment and feel they would monitor me closely than my gastro.

Florence

[Guest guest]

Thanks for the info, Claudine. Boy you have been bizzy bizzy bizzy with

the research, haven't you?

Claudine Crews wrote:

>

> This is the study I was thinking of that had a 100% response to a pegylated

> interferon + ribavirin for genotypes 2 and 3. UNFORTUNATELY I was wrong, it

> is ONLY genotype 2!! There were no genotype 3's in this study, so who knows

> how they would have done. I do believe that genotype 3's respond fairly

> well too though, much better than genotype 1's. Also, please note that this

> study was of Roche's Pegasys, which has a longer half-life than the

> Schering-Plough version. If nothing else it is interesting and optimistic!

> Claudine

>

> Treatment of HCV with Long-Acting " Pegylated " Alfa * Interferon Shows

> Impressive Results

>

> For 16 patients with genotype 1, end-of-treatment response rate is 63%;

> for

> 4 patients with genotype 2, sustained response rate is 100%

>

> by Harvey Bartnof, MD

>

> There were several abstracts today that addressed the experimental

> pegylated

> forms of alfa * interferon. Pegylated means that the active drug is

> encased

> in a fat molecule called polyethylene glycol, or " peg " in an

> abbreviated

> acronym. This slows the metabolism significantly, allowing for a once

> weekly

> injection instead of the 3-times weekly approved dosing for the

> non-pegylated form. The version from Hoffman-La Roche will be called

> Pegasys

> (pegylated interferon alfa-2a, while the version from Schering-Plough

> will

> be called Peg-Intron (pegylated interferon alfa-2b).

>

> Hoffman-La Roche's Pegasys

> A phase II, single arm, open-label study was presented that combined

> Roche's

> Pegasys with Rebetol (ribavirin) for the treatment of chronic infection

> with

> hepatitis C virus (HCV). The lead author was M. Sulkowski, MD, from The

> s Hopkins University School of Medicine. Even though there were

> only 20

> patients, the results were impressive. Sixteen of the patients had

> genotype

> 1, which is the most difficult to treat. The other four patients had

> genotype 2, which is more responsive to treatment. All 20 patients had

> chronic hepatitis C. This was defined as (1) a persistently elevated

> blood

> ALT (alanine aminotransferase, liver enzyme); (2) an HCV RNA viral load

> greater than 2,000 copies per milliliter using the Amplicor Monitor

> test;

> and (3) an abnormal liver biopsy sample consistent with " compensated

> non-cirrhotic liver disease. " All patients were therapy-naove (never

> treated

> for hepatitis C). Exclusion criteria included heart disease, kidney

> disease,

> pre-existing severe depression or other psychiatric disorders, seizure

> disorder, retinopathy (eye disease), other liver diseases, and HIV

> infection.

>

> The dosage was once-weekly Pegasys (180 micrograms) injection under the

> skin

> plus oral Rebetol 1,000-1,200 mg daily. Since genotype 1 is more

> refractory

> to therapy, the duration of treatment for those patients was 48 weeks,

> if

> there was a normal ALT or undetectable HCV viral load at 24 weeks. For

> those

> with genotype 2, the treatment duration was 24 weeks. Those durations

> reflect the standard guidelines based on genotype testing. The median

> baseline HCV viral load was not stated.

>

> The results showed that for those patients with genotype 1, the

> end-of-treatment response was 63%. That means that 63% had an

> undetectable

> HCV viral load (limit 100 copies per milliliter) at the end of 48 weeks

> of

> therapy. (All results are reported using a stricter " intent-to-treat "

> analysis, meaning that all enrolled patients are included.) Whereas,

> for

> those patients with genotype 2, the sustained response rate was 100%.

> (Those

> with genotype 2 received 24 weeks of therapy, followed by a 24-week

> treatment-free follow-up period.) While the numbers of patients are

> small,

> these viral load undetectability rates are among the highest ever

> reported

> for patients treated for hepatitis C.

>

> When the results of the entire 20 patients were analyzed together, at

> the

> 48-week time point, the following were found: the percentage with a

> normal

> ALT was 60%, while those with an undetectable HCV viral load was 70%.

> Interestingly, the percentage with an undetectable viral load at 12

> weeks

> was also approximately 70%.

>

> Adverse events included lowered blood cell counts, which are known side

> effects. The neutrophil (white blood cell) count and hemoglobin

> (oxygen-carrying molecule in red blood cells, lowered in anemia)

> stabilized

> at week four. The decrease in blood platelets (for normal clotting)

> stabilized by week 12. No patient withdrew from the study due to

> abnormal

> laboratory test results.

>

> Two patients (10%) withdrew prematurely from the study. One had a

> seizure

> ( " convulsion " or " fit " ), while another had bleeding in the back of the

> eye

> (retinal hemorrhage). Interferon has been associated with a lowered

> seizure

> threshold in past studies. The hemorrhage was not depicted further in

> the

> poster presentation. However, eight patients did have dosing changes,

> due to

> adverse events. Four changes were due to anemia and two were due to

> neutropenia. Six other patients had a dose modification due to " other

> adverse events. "

>

> The patients will be followed for a longer period. The poster did not

> state

> whether liver biopsies would be performed at the end of the observation

> period. The evaluation of a liver biopsy correlates much better with

> long-term disease progression. HCV viral loads do not necessarily

> correlate

> with long-term outcome.

>

> Even though these results are only interim, the authors conclude that

> the

> combination of Pegasys and Rebetol " appears to have acceptable

> tolerability

> and promising antiviral activity in the treatment of chronic hepatitis

> C. "

> It is quite possible that the sustained response rate for those with

> genotype 1 will be lower than the end-of-treatment response (ETR) rate.

> Often, this is the observed pattern. However, an ETR of 63% for

> genotype 1

> is higher than has been reported for any other therapy(ies) to date. It

> appears that significant advances are being made in the treatment of

> this

> disease.

>

> In a separate poster presentation, the half-life (amount of time for

> half of

> an original amount to be remaining) of Pegasys was found to be 77

> hours,

> while a standard interferon injection had a half-life of nine hours.

> The

> phase II dose-ranging study had 20 HCV negative volunteers. The

> remainder of

> the study evaluated pharmacokinetic and pharmacodynamic (metabolism

> measurements) of Pegasys. The authors determined that the weekly

> self-injected dose under the skin would be 180 micrograms. The lead

> author

> was N.E. Algranati, MD, from Hoffman-La Roche.

>

> Schering Plough's PEG-Intron

> Another poster addressed a different formulation of the same drug.

> PEG-Intron (pegylated Intron, interferon alfa-2b, Schering-Plough)

> injected

> under the skin once weekly showed the same or better anti-HCV effects

> as

> standard Intron-A dosed at 3 million units injected 3-times weekly. The

> pharmacokinetics and pharmacodynamics (metabolism measurements) of this

> long

> acting form of the drug were measured in a 24-week study of HCV

> positive

> patients. The half-life (time for an original amount to be reduced by

> half)

> of PEG-Intron was calculated to be 54 hours, compared to 8 hours for

> standard Intron-A. No unexpected adverse effects occurred. Common

> symptoms

> include " flu " -like symptoms. Abnormal laboratory values included a low

> white

> cell count (neutropenia) and a low blood platelet count (for normal

> blood

> clotting, thrombocytopenia). The weekly dose will be 0.5 micrograms per

> kilogram once weekly (weight in pounds X 0.454 = weight in kilograms).

> The

> lead author was Glue, MD, from Schering-Plough.

>

> * Note that all generic versions use the spelling 'alfa' and not

> 'alpha.'

>

> 11/7/99

>

> References:

> Algranati NE and others. A branched methoxy 40 KD/ polyethylene glycol

> (PEG)

> moiety optimizes the pharmacokinetics (PK) of peg-interferon alpha-2a

> (PEG-IFN) and may explain its enhanced efficacy in chronic hepatitis C

> (CHC). Abstract and poster presentation 120 at the 50th Annual Meeting

> of

> the American Association for the Study of Liver Diseases. Dallas,

> Texas;

> November 5-9, 1999. Hepatology 30(4) Supp2, 190A. Glue P and others.

> Peg-interferon-alpha-2b: pharmacokinetics, pharmacodynamics, safety and

> preliminary efficacy data. Abstract and poster presentation 115 at the

> 50th

> Annual Meeting of the American Association for the Study of Liver

> Diseases.

> Dallas, Texas; November 5-9, 1999. Hepatology 30(4) Supp2, 189A.

> Sulkowski M

> and others. Combination therapy with peginterferon alfa-2a (PEG-IFN)

> and

> ribavirin in the treatment of patients with chronic hepatitis C: a

> phase II

> open-label study. Abstract and poster presentation 145 at the 50th

> Annual

> Meeting of the American Association for the Study of Liver Diseases.

> Dallas,

> Texas; November 5-9, 1999. Hepatology 30(4) Supp2, 197A.

>

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[Guest guest]

Claudine,

Thank you. You're a doll. I'll wait for Peg to be administered by my HMO

if I dont hear from the trial before than.

Thanks..but please post any info or direct me if needed.

Take care,

Florence

[Guest guest]

Claudine,

Thank you. You're a doll. I'll wait for Peg to be administered by my HMO

if I dont hear from the trial before than.

Thanks..but please post any info or direct me if needed.

Take care,

Florence

[Guest guest]

Claudine,

Thank you. You're a doll. I'll wait for Peg to be administered by my HMO

if I dont hear from the trial before than.

Thanks..but please post any info or direct me if needed.

Take care,

Florence

[Guest guest]

Claudine,

Thank you. You're a doll. I'll wait for Peg to be administered by my HMO

if I dont hear from the trial before than.

Thanks..but please post any info or direct me if needed.

Take care,

Florence