New Studies

Not sure if all of these have been posted, but some very interesting stuff from DDW 2007.

1. A Follow-up Week 12 Viral Count Is Useful in Predicting SVR and Is 100% Accurate in Patients without Cirrhosis

http://www.hivandhepatitis.com/2007icr/ddw/docs/060107_a.html


2. Statins Improve Sustained Response to Interferon-based Therapy in Small Study

http://www.hivandhepatitis.com/2007icr/ddw/docs/052507_a.html

3. Treatment of Chronic Hepatitis C in Older Patients

http://www.hivandhepatitis.com/2007icr/ddw/docs/060107_b.html

A more complete listing of HIVandHepatitis.com's coverage of DDW 2007,
here: http://www.hivandhepatitis.com/2007icr/ddw/main.html

[frijole]

Got another link for #3?  It is the same as # 1 BUT the b in front of the html shows me an error in the link.

ha ha -- always looking for references for the "older" patient.

bean

[jmjm530]

It would be interesting if the above study broke down the research group into groups reflecting viral response.  My doc suggested I extend tx due to my age (58) in spite of my RVR, but I could never get any figures (from him or anyone) if elderly RVRs had a significantly less chance of SVR or the same chance (or even a better chance) than younger patients. You would think the data is there somewhere if someone was motivated to extract it.

-- Jim

[jmjm530]

The link for works for me.

Here it is again.
http://www.hivandhepatitis.com/2007icr/ddw/docs/060107_b.html

But in case your browser is as old as you (or I am) here is some copy:

Treatment of Chronic Hepatitis C in Older Patients
By Liz Highleyman

Because hepatitis C typically causes slow liver disease progression, many patients are diagnosed years after initial infection, after they have already developed advanced disease.

Two recent studies presented at the Digestive Disease Week 2007 meeting last month in Washington, DC, and one published in the March 31, 2007 advance online edition of the American Journal of Gastroenterology, looked at the relationship between older age and response to treatment for chronic hepatitis C.
Study 1

The Association of German Independent Gastroenterologists, in cooperation with Roche, is conducting a nationwide observational study to determine the quality of treatment for chronic hepatitis C in routine clinical practice. Between March 2003 and May 2006, data from 11,700 patients were collected at more than 500 centers.

The researchers conducted a cross-sectional analysis of all patients older than 60 years (n = 1529; 13.1% of the entire cohort) who started a treatment with pegylated interferon plus ribavirin, assessing efficacy, tolerability, and adherence.

In the over-60 subset, 43.5% of the treated patients were male, 96.2% were Caucasian, mean age was 65.2 years, mean duration of HCV infection was 18.1 years, mean body mass index (BMI) was 26.1 kg/m2, 30.9% had severe fibrosis or cirrhosis (Desmet-Scheuer stage F3/F4), 26.5% had GFR (kidney filtration rate)  60 years with other usually studied populations reveal that due to poorer conditions at the beginning of treatment, therapy has to be discontinued very often especially for poor tolerability,� the researchers concluded.

They added that in this group of patients, careful management is necessary to prevent the escalation of adverse events leading to treatment discontinuation.

Center of Gastroenterology, Berlin; Center of Gastroenterology, Dortmund; Center for Gastroenterology and Hepatology, Duesseldorf; Center of Gastroenterology, Hannover; Center of Infectiology, Frankfurt; Center of Gastroenterology, Bad Schwalbach; Center of Gastroenterology, Krefeld; Livercenter, Berlin; Center of Gastroenterology, Goettingen; Center of Gastroenterology, Minden; Center of Gastroenterology, Schwetzingen; Center of Gastroenterology, Paderborn; Center of Gastroenterology, Herne; BU Hepatitis/HIV/Infectiology, Roche Pharma AG, Grenzach-Wyhlen, Germany.
Study 2

Japanese patients with chronic hepatitis C currently being treated with interferon-based therapy are generally 10-15 years older than those in the United States. In the second study, Japanese investigators conducted a study to examine the effect of age on the efficacy and safety in patients treated with pegylated interferon plus ribavirin.

The study enrolled 158 consecutive chronic hepatitis C patients with genotype 1 and high viral load (> 100 KIU/mL). The mean age was 55 years, and about two-thirds were male. Participants were scheduled to receive 1.5 mcg/kg once-weekly pegylated interferon alpha-2b (PegIntron) plus daily weight-based ribavirin (800-1000 mg) for 48 weeks.

Patients were assessed for efficacy, safety, and tolerability every 2-4 weeks. Endpoints were SVR and dose modification or premature discontinuation of therapy due to adverse events or laboratory abnormalities.

Results

�         66 of 158 patients (42%) achieved SVR.

�         Multivariate logistic regression analysis revealed that patient age 150x103/mcL (risk ratio 4.55) were independently associated with SVR.

�         32% of patients required dose reduction of ribavirin or pegylated interferon.

�         3% discontinued ribavirin and 19% discontinued all therapy.

�         Accordingly, just over half the patients (53%) required either dose modification or discontinuation of combination therapy due to adverse events.

�         Multivariate analysis revealed that patient age and white blood cell count were independently associated with the dose reduction or discontinuation of combination therapy.

�         Patient age (>60 years), hemoglobin level at baseline (<14 g/dL), and ribavirin apparent clearance (<10 L/hour) were significantly associated with a decrease of a hemoglobin level to below 10 g/dL.

Conclusion

�These results demonstrated that patient age was one of the important risk factors for dose modification and discontinuation of therapy that resulted in decreased efficacy,� the investigators concluded. �Aged patients may be difficult to be treated with ribavirin even in combination with peginterferon instead of standard interferon.�

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Okayama, Japan; Okayama Hepatitis C Research Group, Okayama, Okayama, Japan.
Study 3

Finally, Italian researchers conducted a study to evaluate the effect of age on the treatment of chronic hepatitis C with pegylated interferon alpha plus ribavirin. They retrospectively reviewed medical records of 153 adult patients with chronic HCV infection treated with combination therapy; 30 (19.6%) were 65 years of age or older.
Results

    * In multivariable analysis, all age groups above 40 years had similar odds of achieving SVR (P = 0.71).

    * However, patients over 40 were significantly less likely to achieve SVR compared with younger patients:

          o Age 40-49: odds ratio 0.16; P = 0.006;
          o Age 50-64 years: odds ratio 0.13; P = 0.002;
          o Age 64 and older: odds ratio 0.21; P = 0.037.

    * The effect of age was seen in the 74 patients with genotypes 1 or 4 (P = 0.04).

    * However, among the 79 patients with genotypes 2 or 3, SVR rates were relatively uniform, with no statistically significant differences.

Conclusion

In conclusion, the authors wrote, �The probability of good response to combination treatment with peginterferon alpha plus ribavirin is decreased for patients aged more than 40 years infected with genotype 1 or 4, but patients aged more than 65 had a similar rate of response to those aged 40-64 years. Combination treatment may be safely extended to elderly patients with no major contraindications.�

(The "?" are contained in the abstract but they appear to be typos)

[katerika]

  Patient age (>60 years), hemoglobin level at baseline (<14 g/dL), and ribavirin apparent clearance (<10 L/hour) were significantly associated with a decrease of a hemoglobin level to below 10 g/dL.

I hope this question isn't too stupid to answer.
Forgive me for making random connections, do I understand that we clear or peak effect for riboviran is 10 hours? If this is the case wouldn't there be less chance of dropping hemeglobin levels if we took the dosage 10 -12 hours apart?


I am sorry if I am way out there, You know I'm on drugs with an 11 heme.
Teri

[geterdone]

Correct me if I am wrong and am still trying to get an understanding of this myself but wouldn’t the () 60 plus years with a baseline of < 14 g/dL (minus) meaning below 14 g/dL and ribavirin apparently peaks 2 hours after taking is where significant decrease of hemoglobin had gone below 10 g/dL and then build back up over the remaining 10 hours.

The ribavirin is a 12 hour drug, which makes sense to me why some feel so lousy shortly after taking the riba and then the drug decreases over the course of the remaining hours until the next dose.

Again, I may be reading this all wrong.

Jasper

[jmjm530]

Not exactly sure about the above ref to riba clearance. My understanding is that riba has a very long half life -- 10-12 days  I think -- and therefore dose timing is not very important unless very high doses -- over 2000 mg/day -- are used. In those cases, a Sweedish study suggests multiple daily doses (3 or more) because of the saturability of ribavirin. I often took my two doses of ribavirin as close as 4-5 hours apart, due to my quirky meal schedule while on treatment.

-- Jim

[geterdone]

Too bad MH does not have a pharmacologist on staff to help explain the drugs and duration of each or someone who has the time to research a little further.

I think it has a lot of importance no matter what dose you’re taking. The 10-12 days in my thinking is that after the body has reached the sustained saturation level over a duration of time there is a continuum (level) reached in the blood system which after stopping the riba there is a residual residue left in the blood stream and it takes 10 to 12 days to completely clear the body.

Also in the Study 2 posted it is based on the Japanese people which are small frame and lighter than Americans in the age group which would also coincide with the riba dosing of 800 to 1000mg in the study.

I know that for me personally when taking the riba it takes anywhere from about 1 and a half hours to start feeling it and at about 2 hours to start getting the ghost look and a big drop into fatigue which last anywhere from the next 3 to 4 hours.

Anyway this is a very interesting subject.

Jim was that every 4-5 hours? Or 3 in the late morning and 3 in the early afternoon for a higher concentration.

jasper

[jmjm530]

I assume you're talking about my own ribavirin schedule.

For most of treatment  I took 1200 mg/day of riba in two doses. 3 pills first dose and three pills second dose.

Because of eating problems/issues, I only ate twice a day, trying to get as many calories into those meals as possible.

I took my first dose of riba with breakfast. Breakfast was anytime between 9AM and 12PM, depending on when I felt 'hungry' (really "able to eat" would be a better phrase).

I took my second dose with my second meal, which might have been anywhere between 12PM and 5PM. Again, the timing of my second meal had to do with when I felt 'hungry'.

For that reason, it was not unusual on a given day to take my riba at let's say 10AM and 2PM. Or on another day at 11AM and 4PM, etc.  I did try, however, to make a conscious effort not to take my riba less than 3 hours apart, and on a typical day the does were probably 5-7 hours apart.

As you can see, my riba schedule was driven by my eating schedule which was in turn driven by only what I could describe as a significant eating disorder from the treatment drugs. My liver specialist had no problem with my riba dosing schedule and at one point he told me that as far as he was concerned, I could take all the ribavirin at one sitting, given it's long half life. That said, a later study -- on the saturability of ribaviri -- would prove him wrong, since apparently the body can only absorb so much ribavirin with maxium effectiveness at one time, and probably not 1200 mg. Also, the few times that I did take a double-dose (1200mg) at one time -- by accident -- I did feel a noticeable "rush", so would not recommend that to anyone. However, I never had any problems when I took my normal doses 4-5 hours apart. I'm just sharing my personal experience and non-professional opinions here. All speak to your doctor or nurse what is the best time for you to take your medications.

-- Jim

[geterdone]

Thanks for sharing.
jasper

[getnbetter]

Another good clinical trial link is www.clinicaltrials.gov, this is where I found my albuferon trial I am in.