Gloria

[Guest guest]

Not at all, BethI'd already damaged my liver with my drinking, then I quit the same year that I believe I was infected. However, I'm sure that I help my liver to get so damaged, by my addiction to Acetaminophen. Honestly, I was not very nice to my liver at all.GloriaI have read that tx can cause cirrohsis. Chance are slim but can happen. I guess maybe that is what I was asking that maybe the tx did it; but since you were already stage 3 maybe not. Always reading and thinking.

Yup - "The Confusion" is just what I was trying to say awhile back. We all have to be extremely careful in suggesting to new heppers, that perhaps treatment will only be for 24 weeks or that it's got an overly high percentage of cure rate. It's too encompassing to just flatly suggest, that's what will happen.

Telaprevir and Boceprevir Understanding The Chance For A Cure

The Good News Today Vertex's drug Telaprevir Received FDA Priority Review" both in U.S. and

Canada. On Jan 6th Mercks Boceprevir received FDA Priority Review and EMA Accelerated Assessment. Telaprevir and boceprevir have been deemed the new generation of drugs both of

which appear to be able to improve sustained response while shortening duration of therapy. The Confusion The headlines on these two drugs have been misleading and confusing for anyone newly diagnosed. With tag lines reading; "New Hepatitis C Drugs Telaprevir, and Boceprevir can boost cure rates as high as 75 percent with only 24 weeks of treatment". Okay, maybe I embellished a bit, but you get the gist of what I am trying to convey. If I were new to the world of hepatitis C my assumption would be I had a 75 percent chance at a cure. I may even assume treatment duration would be

at 24 weeks. However, there are many factors to consider when figuring in these cure rates. Boceprevir and telaprevir will improve the chance for achieving a cure, but a 75 percent cure rate will not be seen in all people treating HCV. The cure rate for these drugs differ and hinge on genotype, treatment naïve patients, relapsers, partial responders, null responders, amount of liver damage/host factors, race and age. The lingo used by physicians or technicians can be difficult to remember; below is a clear definition of these terms. In this blog entry I hope to establish a better understanding in relation to achieving SVR/cure when treating with telaprevir or boceprevir. Learning The Buzz Words Cure-Among patients the word "Cure" has had its share of controversy. The definition deemed a

cure by

researchers/scientist or physicians is defined as having no detectable levels of the virus for more than six months after stopping treatment. *Follow-up studies have shown no trace of the virus in the blood or liver for

over 10 years. SOC - Standard of care therapy for hepatitis C is a FDA approved regime consisting of pegylated

interferon and ribavirin. When treating with standard of care alone the chance for SVR is approximately 40 to 50 percent for people with genotype 1, and 80 percent or more with genotypes 2 and 3. SVR- sustained viral response; A negative viral load test six months after the completion of therapy is predictive of sustained virologic response. In contrast, failure to achieve a 100-fold reduction in viral load by week 12 of therapy has a strong negative predictive value for sustained virologic response and suggests that treatment is likely

ineffective. What Is A 100-fold reduction in viral load ? Changes in viral load are sometimes expressed in terms of logs: a 1-log change means a 10-fold increase or decrease; a 2-log change is a 100-fold increase or decrease. What Is A 2 Log Drop? Example: 2 log drop = 15,000,000 IU/Ml to 150,000 IU/mL; a viral load that starts at 15,000,000 IU/mL and does not decrease to 150,000 IU/mL or lower. Genotype Genotype refers to the genetic make-up of an organism or a virus. Six genotypes (numbered 1–6) and more than 50 subtypes (identified by

lowercase letters, e.g.,

1a and 1b) have been identified. Genotype 1 is the most common genotype seen in the U.S. and the most difficult to threat. HCV genotype is the strongest predictor of responses to IFN-based therapy. HCV is an RNA virus related to the flavivirus family. RNA viruses are genetically less stable than DNA viruses and are prone to mutate during replication. It’s a common misconception that hepatitis C is just one virus, but in reality (as a result of mutation over hundreds of years), it’s a group of very closely related strains. They are similar enough to be called HCV, but based on genetic differences, they can be classified into distinct groups called genotypes. Host Factors The presence of bridging fibrosis and cirrhosis has been reported as one of the most unfavorable predictors for IFN-based therapy. Several studies

have

demonstrated that SVR rates are lower in patients with coexistent insulin resistance and/or hepatic steatosis or steatohepatitis. Racial differences in response to efficacy of IFN exist and have been one of the host factors. clinical Trials with IFN-ribavirin combination therapy

demonstrated that SVRs were highest among Asians (61%), followed by Whites (39%), Hispanics (23%), and African-Americans (14%) . Hispanics and African-Americans were less likely to respond to PegIFN-α-ribavirin compared to Whites . ( host factors are discussed below in the trial results for telaprevir/boceprevir)

Familiar Treatment Terms Response guided treatment- Or viral load monitoring during treatment is intended to enable the physician to determine the duration of combination therapy based on a patients viral response. *Note Boceprevir protocol below Naïve- No prior treatment/first time treating HCV. Relapsers- People whose viral load drops to an undetectable level with treatment but rises again after treatment ends. Partial responders- People who have at least a 2 log10 (100-times) drop in viral load, but do not reach undetectable levels in the blood by

week 24.

Null responders- People who failed to reduce their viral load by at least 2 log10 (100 times) after 12 weeks of prior treatment, which is the currently recommended Food and Drug Administration (FDA) definition for clinical trials of investigational hepatitis C treatments. Terms Used In Response guided treatment (RVR)-Rapid Viral Response; Is an undetectable viral load four weeks into treatment. In SOC if you have an RVR your chance of cure is better than 78% and 92% and your doctor may recommend that you shorten your treatment. (cEVR) Complete early viral response- Is an undetectable viral load 12 weeks into treatment. If you have a complete EVR you have a good chance of being cured . (pEVR) Partial early viral response - A drop in viral load of at least 2-log (e.g. from 600,000 IU/mL down to 6,000 IU/mL) at 12 weeks of treatment, but still detectable virus in your blood. In people with genotype 1 the chance of viral clearance is low and treatment is generally stopped. (non-EVR) Non-response- No significant drop in viral load in the first 12 weeks of treatment. ______________________________ Telaprevir: Treatment In Genotype 1 *Naïve In the Phase III ADVANCE trial What is the ADVANCE Trial? In ADVANCE investigators compared two telaprevir-based regimens with standard therapy in 1,088 treatment-naive patients with chronic genotype 1.

What Patients Were Treated For Only 24 Weeks ? Patients Who Achieved RVR. Patients who achieved extended, rapid virologic response (RVR) – defined as undetectable viral load (HCV RNA) at treatment

weeks 4 and 12 – were treated with standard therapy for an additional 16 and 12 weeks, for a total of 24 weeks. Significantly improved SVRs were also observed in difficult-to-treat subgroups; Among black patients, the [sVR] rates were 58% and 62% in the 8- and 12-week treatment arms, and 25% in the control arm*which is SOC, and in cirrhotic patients the respective rates were 53%, 62%, and 33%. What where the results? Cure Rate=75% ______________________________ Telaprevir: Treatment In Genotype 1 *Failed to respond to prior therapy In the Phase III REALIZE trial What is the REALIZE trial? REALIZE is a pivotal Phase 3 clinical trial of telaprevir in combination with peginterferon alfa-2a (PEG) and ribavirin (RBV) in 662 people with genotype 1 chronic hepatitis C who

"failed" to achieve sustained virological response (SVR or viral cure) with prior pegylated interferon-based therapy. The trial evaluated the safety, efficacy and tolerability. Who Was Enrolled In The Trial And What Were The Results ? Patients in the study were enrolled based on their response to prior

treatment: Out Of 662 Enrolled In The Study 53% were prior relapsers or 354 relapsers What were the results ? Cure Rate= 86% ______________________________ Out Of 662 Enrolled In The Study 19% were prior partial responders or 124 partial responders What were the results ? Cure Rate=57% _________________________________ Out Of 662 Enrolled In The Study 28 percent were prior null responders or 184 null responders What where the results ? Cure Rate=31% ________________________________ Tell Me More About The Host Factors In this study, 26% of patients overall had cirrhosis and 89% of patients overall had a high viral load (HCV RNA More Then 800,000 IU/mL) when entering the study. Specifically in the null responder population, there were an even greater number of people with cirrhosis (33%) and high viral load (95%). Approximately 50% of patients were genotype 1a and 50% were genotype 1b. Boceprevir Treatment In Genotype 1 *Naïve HCV SPRINT-2, examined patients with hepatitis C with genotype one who had not yet been treated with the standard treatment. The treatment protocol consisted of a 4 week

lead-in phase of PegIntron plus

ribavirin (without boceprevir), followed by the triple combination of boceprevir, PegIntron and ribavirin. Duration and continuation of treatment was guided by the type of on-treatment response to the medications.* By using a lead-in strategy it can aid physicians in identifying the patients response to interferon before adding boceprevir. This also will provide an early indication of the likelihood of treatment success. An additional advantage of response-guided therapy is it can enable physicians to be flexible in managing their patients’ therapy by adapting treatment duration to individual patient response. What Were The Results ? The SVR Rates according to the different treatment arms are listed below: a. If HCV RNA (viral load) negative at week 8 through week 24, triple

therapy was continued for a total treatment duration of 28 weeks; Cure Rate = 63% a. If HCV RNA positive at week 8 but undetectable at week 24, boceprevir was stopped at week 28 and PegIntron/ribavirin combination therapy (without boceprevir) was continued for a total treatment duration of 48 weeks; Cure Rate = 66% a. The control arm was *standard of care – PegIntron plus ribavirin only—with a treatment duration of 48 weeks; Cure Rate= 38%. African Americans/Blacks—Treatment Response There were also 159 African American/Black patients in the study—African Americans/Blacks comprised 15%

of the

patient population in this trial. The SVR rates by different treatment arms are listed below: a. If HCV RNA negative at week 8 through week 24, triple therapy was continued for a total treatment duration of 28 weeks: Cure Rate= 42% a. If HCV RNA positive at week 8 but undetectable at week 24, boceprevir was stopped at week 28 andPegIntron/ribavirin combo therapy without boceprevir) was continued for a total treatment duration of 48weeks; Cure Rate= 53% a. The control arm was *standard of care – PegIntron plus ribavirin only—with a treatment duration of 48weeks; Cure Rate= 23%. *If the virus was detected in any patients;(HCV RNA positive ) at week 24

all

treatment was stopped. Boceprevir Treatment In Genotype 1 “treatment-failure†The RESPOND 2 study included 403 HCV genotype 1“treatment-failure†patients. The patients were comprised of null responders, nonresponders and relapsers. In all study arms, previous relapsers and previous null responders fared better than prior nonresponders. The study included a 4 week lead-in phase of PegIntron plus ribavirin(without boceprevir), followed by the triple combinationof boceprevir, PegIntron and ribavirin and treatment duration was based on type of on-treatment response. What Were The Results ? The SVR rates and duration of treatment periods for all patients are listed below; a. If HCV RNA negative at week 8 and at

week 12 the

total treatment duration was 36 weeks; Cure Rate= 59% a. IF HCV RNA positive at week 8, but undetectable atweek 12, boceprevir was stopped at week 36 and the combination of PegIntron/ribavirin was continued for a total treatment duration of 48 weeks; Cure Rate= 66% a. Control arm was *standard of care – combination of PegIntron plus ribavirin only—for a total treatment durationof 48 weeks; Cure Rate= 21% *If any patients were HCV RNA positive at week 12 all treatment was stopped It is important to know that the treatment duration in the boceprevir containing arms were 28, 36 or 48 weeks depending on the type of on-treatment response. The Side Effects Telaprevir Telaprevir ILLUMINATE trial There were more adverse event–related treatment discontinuations in the longer-treatment group (12.5% vs. 0.6%), suggesting a benefit to the shorter-duration therapy Telaprevir ADVANCE trial Rates of treatment discontinuation due to adverse events, such as rash and anemia, were 8% and 7% in the 8- and 12-week in telaprevir groups compared to SOC, which was at 4% . Formally known as Protease Inhibition of Viral Evaluation 3 (PROVE3). Quote from McHutchison, MD:"The benefit of adding telaprevir, however, was offset somewhat by significant side effects. About half of those receiving telaprevir developed a rash, and 5 percent of those who did so had to stop therapy because the rash was severe. Patients who received telaprevir-based therapy were

also more likely to discontinue therapy (50 of 339, or 15 percent) than were patients who received standard therapy (5 of 114, or 4 percent). "While it is true that patients receiving all three drugs were more likely to experience side effects, especially rash and anemia, the benefit of the regimen can be substantial," said McHutchison. "Adding

telaprevir to standard treatment for hepatitis C is very helpful to large numbers of patients who originally failed to fully respond to previous treatment." Drug Rash with Eosinophilia and Systemic Symptoms due to Telaprevir. Dermatology. 2010; 221(4):303-5. Epub 2010 Aug 25. Summary We report a case of drug rash with eosinophilia and systemic symptoms (DRESS) due to telaprevir (VX-950), a specific inhibitor of the hepatitis C virus (HCV) serine protease. A 57-year-old woman with chronic hepatitis C was included in a phase 2 rollover study of VX-950. She received VX-950 in combination with pegylated

interferon alfa-2a and

ribavirin. Six weeks later, she developed a generalized pruritic maculopapular exanthema with malaise, fever, dyspnoea and lymph node swelling. She had an eosinophilia (up to 2.7 x 109 cells/l), large activated lymphocytes and increased concentrations of aminotransferases. Histological examination of a cutaneous biopsy was consistent with a drug rash reaction. The HCV treatment was stopped, and she was treated with topical and oral steroids. Cutaneous and systemic symptoms disappeared within 1 month. Telaprevir was considered the culprit drug. We report to our knowledge the first case of DRESS syndrome due to telaprevir. The safety data of telaprevir is derived mainly from the PROVE1, PROVE2 and PROVE3 studies. They showed a high frequency of cutaneous side effects reported under the imprecise terms of pruritus and rash, leading to an increased rate of treatment discontinuation. Telaprevir, due to its efficacy, is probably on the way to obtaining

regulatory approval in the near future. It is therefore important to be aware of the high incidence of cutaneous side effects and better describe them. Our observation suggests that potentially severe hypersensitivity reactions may belong to the spectrum of rashes induced by this drug. Affiliation Department of Dermatology, University Hospital of Nice, Nice, France. Journal Details Name: Dermatology (Basel, Switzerland)ISSN: 1421-9832 Source

The Bottom Line: Safety and Tolerability Information for ADVANCE, ILLUMINATE and REALIZE The safety and tolerability results of telaprevir-based combination regimens were consistent across the Phase 3 studies. The most common adverse events (AEs) were rash, fatigue, pruritis, headache, nausea, anemia, insomnia, diarrhea, flu-like symptoms and pyrexia with the majority being mild or moderate in severity. Rash and anemia occurred more frequently in the telaprevir treatment arms compared to the control arms.Rash was primarily characterized as eczema-like, manageable and resolved upon stopping telaprevir. More than 90% of rash was mild to moderate and was primarily managed with the use of topical corticosteroids and antihistamines. Anemia was

primarily managed by reducing the dose of ribavirin. Erythropoiesis-stimulating agents (ESAs) were used in only 1% of people in the Phase 2 and Phase 3 studies. Discontinuation of all

drugs due to either rash or anemia during the telaprevir/placebo treatment phase was 1% to 3% in the telaprevir treatment arms. Boceprevir SPRINT-2 trial-"Treatment appeared to be associated with two side effects compared with placebo -- anemia and a distorted sense of taste, or disgeusia. Overall, patients on treatment had greater use of erythropoietin "Note (rescue drugs)" to treat anemia compared with controls (43% for short- and full-course, versus 24% of those on placebo). More boceprevir patients also had to reduce their treatment dose due to anemia (20% and 21% versus 13%).Other adverse events included nausea, headache, and fatigue, at similar rates across all three groups". RESPOND-2 trial -- genotype 1 patients who'd failed prior therapy; Anemia also appeared to be problematic for the treatment groups in the 403-patient

study. Unfortunately according to previous clinical studies the two new drugs did not seem to lessen side effects of HCV treatment, they are however likely to improve efficacy. Which is really the bottom line, improved SVR rates with shorter treatment duration. The best combo we have had thus far ! Additional Information: Hepatitis C:New direct-acting antivirals' combination/2011 (IL28B) Genotype Test Likeihood Of Achieving SVR

Information On Both The RESPOND 2 , HCV SPRINT-2, from HCV Advocate Fact Sheets.

http://Hepatitis Cnewdrugs.blogspot.com/2011/01/hepatitis-c-news-telaprevir-and.html

[Guest guest]

When do you go to Drs again ? Wanted you to know that you are

always on my mind. You may be alone physically , but not in spirit.

You can't get rid of us that easy. Teach me how to " de-stress " . I've

always been a worry wart; this stuttering isn't gonna quit till I

learn how to not worry...ummm, seeing four specialist in Feb and

March, now how was I gonna de-stress?

http://facebook.com/people/andTrudy-Kinsey/1340460877 "

" A well- behaved woman never made history " ...Mae West

http://oktravels.wordpress.com

http://allrecipes.com/cook/TrudyK/profile.aspx

[Guest guest]

This is late due to I was in the hospital with the pnemonia.

I am glad to see this for real Gloria. I was going to hire this one girl to help me during tx. She is 22 and dumb as a board. Every time she texts me she asks if Rick is here or going to be here when she comes over. I am done. She is not going to help. Me. She told me she can do frozen pizza and frozen meals that is it. Shit I can do that. Forget it. I was hoping she would cook a couple casseroles and help with laundry. Maybe let dogs out help change out their cages clean them up. She can't do any of that. She gave me a list of the food she likes though and should get if she spends any nights. She is so outta here. My husband went to the pharmacy tonight to get himself some meds for himself after a doc appt he has the flu. She sees him and instantly is right there with him. Asked if I were out. Then dropped me and started asking about him. He told her he was sick and she had better get away so she did not get sick. He said she got a blank look

turned around and walked off. She has a bad crush on my husband. He is definitly not into her. Anyway So will be doing it without much of Ricks help. I think the more he sees the more he will step up like he did when he saw how bad I was with this pnemonia.I knew I was in trouble when the day before the doc appt I had the dogs out in the cold going potty I have to take them on leashes no fence. I knew I was not okay. I about fell face first in the snow. I was barely able to stand the pain in my right side of my lung. I was wondering if my right lung was trying to deflate or something. It was that that was the side the pnemonia was in. He did not see me till I was already in the hospital. Then he was mad he was not the first one to know I was in there. Can't win.

I am out and on the mend I hope. My doc did everything according to my liver care and all too.

PS I know what you feel about people not leaving wills. That is really crappy. Ricks dad did that and now there are a lot of bad vibes and feelings going on between their step brother step mother and them that didn't have to be there.

She did send flowers to the hospital and come to check on me as did Ricks step brothers wife. wierd kind of on the sister in law.

From: Gloria <gadamscan@...>Subject: Re: [ ] Date: Wednesday, January 19, 2011, 11:46 PM

When I did treatment the first time, my husband worked away from home a lot!!! Unfortunately, on the 2nd round, he was right there. In my case, that turned out to be the worst thing that could have happened. Do I wish that I had never done treatment and still had my husband?? NOPE not for a second. He truly was a jackass to me, period. In fact, he's still a jackass to me!!! Dying without a will. Geez!!! I'll tell you, if I could magically wish him back from the ashes, I'd use a baseball bat to hit him up the side of the head.When he

was away during the first treatment, my mother would come over every Friday night that I did my shot. You know, never once did she actually see me do the shot; but, she felt better that I was not alone. However, I actually had no problem with being alone on the Sat. or Sun. That way, I could just stay in bed and was not concerned about anyone.Gloria

The best way to get through this is to use your head. Know why it is you feel bad. You can defuse a lot of the anger just by knowing why you feel that way. I had horrible PMS all the way up to menopause. My husband had a lot to put up with. I finally got to where I told him that I knowticed when I got up and was mad sometimes and haven't even talked to anyone yet or done anything and already felt like blowing up. So I would recognise it and tell my husband wrong side of bed. He knew what it meant and stayed out of my way. I tried harder to avoid stuff on those days to not go off on anyone. I was a little maniac sometimes.

Anyway I started doing nice things for me on those days to help myself. I took a nice bath. I got a back rub from Rick. I slept in and watched tv. I ate ice cream. I looked at meditations on the internet. I did stuff to make me relax and decided the other stuff would have to wait for a better day. You may have to do some of this. Don't let it get you all wound up. They aren't worth it hon. You need to help yourself now. do some constructive stuff for you now. You are not done getting over tx right now. You are expecting to be over it way too fast. Allow yourself the time to get better for now if you can. I know you want to sink all that stupid clinics ship and yes they deserve it and worse but right now it may not be too constructive in your healing. I am worried about you.

I am sitting over here with 105 temp right now. Don't make me come over there and make you take care of you. Me and Teri and Don will all come over and feed you grapes and take care of you. They had a write up in Dons and my City's newspaper saying they would have the two new drugs out sometime this summer. So may be starting this summer. After being sick today with no help and 105 fever and vomiting and chills I had a harder than hell time getting up and putting on three pairs of jogging pants and three long sleeve jogging shirts and socks and a coat so I could take the dogs out. Then back in to take some thera flu and back to bed. Now got a bad headache. I was barely able to get the dogs out today. I asked a friend today if I paid her would she come spend the night with me on shot nights. I am still waiting for an answer. I hope she says yes. Rick is going to get a second job so he won't be able to help me probably at all. Don't know what I

am going to do. He still says he does not want me to tell his step mom. She knows I got to find a way to tell him I told her. I can't go stay with her on shot nights because of my dogs and parrot. My house is not up to her niceness. She will be more helpful for grocery shopping and rides to appts. I got the lady across the fields for that too. I may ask Ricks step mom to go with me for the first shot. I don't think I will have trouble with it. I have given shots to my dogs. I gave shots to my horses too. so we will see.

Good night. Chilling again.

Anyway ny. Love you and no matter what always take time to love yourself and when you have a bad day start looking for the good in it too. It is there you just haven't looked far enough yet. Love you