EPO and SVR

The following is a study on the SVR rates when using EPO. Some interesting results for anyone using or considering EPO to conteract anemia. Even more interest is High Dosing RBV.
Below is the Abstract
CS

Treatment of Chronic Hepatitis C Virus Genotype 1 with Peginterferon, Ribavirin, and Epoetin alpha

Mitchell L. Shiffman, Jennifer Salvatore, Sarah Hubbard, Angie Price, Richard K. Sterling, R. Todd Stravitz, Velimir A. Luketic, and Arun J. Sanyal

Abstract
Successful treatment of chronic HCV with peginterferon (PEGIFN) and ribavirin (RVN) is often limited by anemia. We performed the present study to determine if utilizing epoetin alpha (EPO) with or without a higher dose of RVN could enhance sustained virologic response (SVR). We randomized 150 treatment-naive patients with chronic HCV genotype 1 into 3 treatment groups: (1) PEGIFN alpha-2b (1.5 _g/kg/week) _ weight-based RVN (WBR) 13.3 mg/kg/day (800 to 1400 mg/day); (2) PEGIFN alpha-2b _ WBRVN _ EPO (40,000 U/week); or (3) PEGIFN alpha-2b _ higher dose WBR 15.2 mg/kg/day (1000 to 1600 mg/day)_EPO.We initiated EPO at the onset of therapy to maintain the hemoglobin between 12 and 15 g/dL. When required, we reduced RVN by 200-mg steps. African Americans compose 36% of the population. A significantly smaller percentage of group 2 patients had a decline in hemoglobin to less than 10 g/dL (9% versus 34%; P < 0.05) and required that the RVN dose be reduced (10% versus 40%; P < 0.05) compared to group 1 patients.

Despite this, SVR was similar in these groups (19% to 29%). SVR was significantly greater (P < 0.05) in group 3 patients (49%). This resulted from a significant decline (P < 0.05) in relapse rate; only 8% versus 38% for groups 1 and 2.

Conclusion: We conclude that using EPO in all subjects at the initiation of PEGIFN and RVN treatment will not enhance SVR given the same starting dose of RVN. In contrast, a higher starting dose of RVN was associated with a lower relapse rate and higher rate of SVR. (HEPATOLOGY 2007;46:371-379.)

[CockSparrow]

Edited full study.

The starting dose of EPO was 40,000 IU/week. This was initiated at the start of PEGIFN and RVN treatment in all patients randomized to groups B andCas long as the hemoglobin was less than 15 g/dl. In those patients with a hemoglobin greater than or equal to 15 g/dl we monitored the hemoglobin weekly and we initiated EPO as soon as the hemoglobin declined to less than 15 g/dl. We increased the EPO dose to 60,000 IU/ml if the hemoglobin declined by more than 2 g or if the hemoglobin did not rise by at least 1 g. If the hemoglobin rose to 15 g/dl or greater, we did not administer the weekly EPO dose and we reduced the dose to 20,000 IU/week. Thereafter, we adjusted the dose of EPO between 20,000 and 60,000 IU/weekly or every other week to maintain the hemoglobin within the range of 12 to 15 g/dl.

We monitored the serum hemoglobin at weekly intervals during the first month, at 2-week intervals during the second month, and monthly intervals thereafter as long as the hemoglobin was stable. For those patients in which the dose of EPO or RVN was being adjusted or the hemoglobin was not stable; we measured this more frequently.
We did not use either granulocyte colony stimulating factor or interleukin-11 for treatment of neutropenia or thrombocytopenia, respectively.

We performed 2 types of analyses. In the intention-to-treat analysis, we included all patients who received at least 1 dose of study drug, and we counted those who dropped out of the study as nonresponders regardless of their virologic response (VR). In addition, we also performed a per-protocol analysis. In this analysis, we excluded from the analysis patients who dropped out of the study before their VR could be characterized. Thus, we counted as nonresponders in the per-protocol analysis only those patients who were treated for 12 weeks and failed to achieve EVR, who were treated for 24 weeks and still had detectable HCV RNA, or who developed breakthrough between weeks 24 and 48. We followed patients who stopped both drugs after they were HCV RNA negative, but before week 48, through week 72 and we included them in the analysis as either an SVR or relapse.
We compared the difference in VR rates between various groups by analysis of variance. A P value of 0.05 was considered significant. -

Results
Comparison of Study Groups
Of the 150 patients enrolled into the study, 146 received at least 1 dose of study drug. The remaining 4 patients decided not to start treatment in the protocol after learning of the treatment they had been randomized to receive. Table 1 compares various demographic, biochemical, virologic, and histologic characteristics of the 3 groups at baseline. Themean age of the population was 47 years, 61% were male, 39% were African American, mean body weight was 82 kg, mean serum ALT was 101 IU/l, mean log serum HCV RNA was 5.5 IU/ml, and 5% of patients had cirrhosis. Although no significant differences existed in any of these parameters among the 3 groups, the group treated with standard WBR and EPO (PEGIFN_WBR_EPO) had the highest percentage of African Americans and the highest percentage of patients with cirrhosis.

Virologic Response
VR according to the intention-to-treat analysis at various times during the study are illustrated in Fig. 1A. At week 4, 9%, 8%, and 11% of patients treated with PEGIFN_WBR, PEGIFN_WBR_EPO, and PEGIFN_HDR_EPO, respectively, were HCV RNA undetectable and had achieved an RVR. At week 12, EVR had been achieved in 68%, 65%, and 63% of patients in these 3 groups, respectively. At the completion of 48 weeks of treatment, VR was achieved in 46%, 31%, and 53% of patients in the 3 groups, respectively. The somewhat lower VR rate observed in the group that received standard WBR and EPO (PEGIFN_WBR_EPO) was likely secondary to the higher percentage of African Americans and patients with cirrhosis in this group (Table 1). No significant differences in either RVR, EVR, or VR existed between the 3 treatment groups. The SVR rates observed for the 2 groups who received standard WBR (PEGIFN_WBR and PEGIFN_WBR_EPO) were not significantly different; 29% and 19% for patients in the PEGIFN_WBR and the PEGIFN_WBR_EPO groups, respectively. The group treated with HDR and EPO (PEGIFN_HDR_EPO) had an SVR of 49%; and this was significantly (P_0.05) greater when compared to the 2 groups treated with standard dose RVN. Because the difference between the rates of VR were not significantly different among the 3 treatment groups, any differences in SVR must have been secondary to relapse.

The relapse rates in the 2 groups treated with standard WBR (PEGIFN_WBR and PEGIFN_WBR_EPO) were not significantly different; 36% and 40%, respectively.
In contrast, the relapse rate of the group that received HDR (PEGIFN_HDR_EPO) was only 8%. This 4-fold to 5-fold decline in relapse rate was significantly lower (P _0.05) than observed in the 2 groups treated with standard doses of RVN

ITT Response Rate
PegIFN + WBR
EVR 68%
ETR 46%
SVR 29%
Relapse Rate 36%

PegIFN + WBR + EPO
EVR 65%
ETR 31%
SVR 19%
Relapse Rate 40%

PegIFN + HDR + EPO
EVR 63%
ETR 53%
SVR 49%
Relapse Rate 8%

Percentage of patients with end-of-treatment VR and SVR calculated according to a modified per-protocol analysis. In this analysis, we excluded from the analysis patients who dropped out of the study before their VR could be characterized. Thus, only those patients who were treated for 12 weeks and failed to achieve EVR, were treated for 24 weeks and still had detectable HCV RNA, or developed breakthrough between weeks 24 and 48 were counted as nonresponders. Patients who were HCV RNA undetectable when they prematurely discontinued treatment were followed through the end of the study and included in the analysis.

Modified Per Protocol Analysis
PegIFN + WBR
ETR 51%
SVR 34%

PegIFN + WBR + EPO
ETR 37%
SVR 22%
Relapse Rate 40%

PegIFN + HDR + EPO
ETR 54%
SVR 49%

End-of-treatment VR and SVR rates according to the per-protocol analysis are illustrated in Fig. 2. Overall, we observed slightly higher rates for VR and SVR compared to the intention-to-treat analysis


SVR by Body Weight
Less 65 kg
WBRBV 15%
HDRBV 36%

65-85kg
WBRBV 29%
HDRBV 61%

85-105kg
WBRBV 25%
HDRBV 47%

Greater 105kg
WBRBV 10%
HDRBV 33%

[CockSparrow]

Study Continued

Reduction in PEGIFN Dose
For those patients who completed 48 weeks of therapy, PEGIFN dose reductions were similar across the 3 treatment groups. The percentage of patients with any PEGIFN dose reduction was 14%, 11%, and 19%, respectively. The mean decrease in PEGIFN dose across the 3 groups was 2%, 6%, and 6%, respectively. Only 5%, 11%, and 12% of the patients in the 3 groups received less than 80% of the anticipated total maximal PEGIFN dose.

Impact of EPO on Hemoglobin
The impact of EPO on serum hemoglobin is summarized in Table 2. The mean hemoglobin prior to the initiation of treatment was 15.3 g/dl. This was not significantly different between the 3 treatment groups. The routine use of EPO did not prevent RVN-induced anemia. However, the maximal decline in hemoglobin and the percentage of patients in whom the hemoglobin declined to less than 10 g/dl were significantly lower (P_0.05) in those patients who received standard WBR along with EPO (PEGIFN_WBR_EPO), compared to patients who did not receive EPO (PEGIFN_WBR).

Impact of EPO on RVN Dose
The impact of EPO on the dose of RVN received is summarized in Table 3. The routine use of EPO in patients treated with standard WBR significantly reduced (P _ 0.05) but did not eliminate the percentage of patients who required RVN dose reduction. Although the mean dose of RVN received by patients in the PEGIFN_WBR_EPO group was greater than in patients not treated with EPO (PEGIFN_WBR), this difference was not significant. Patients treated with the higher dose of RVN received on average a mean RVN dose that was significantly (P _ 0.05) greater than the 2 groups treated with standard dose of RVN. However, despite the use of EPO, 31% of patients in this group still required dose reduction by a mean of 102 mg/day. RVN dose reduction did not appear to adversely impact SVR.

Impact of RVN Dose on VR
The impact of RVN dose on SVR is illustrated in Fig.3. Because both the SVR and the mean RVN dose received by the 2 patient groups treated with standard WBR were similar, these 2 groups were combined and compared to the group treated with the higher dose of RVN.
Figure 3A illustrates the impact of RVN dose on SVR in Caucasians and African Americans. Both Caucasians and African Americans had a higher SVR when treated with the higher dose of RVN. In Caucasians, this increased from 27% to 56% and in African Americans this increased from 27% to 31%. In both groups, the increase in SVR was secondary to a reduction in the rate of relapse. Figure 3B illustrates the impact of RVN dose on body weight. Regardless of body weight, patients treated with the higher dose of RVN had a higher SVR.

Reason for Discontinuation of Treatment
The reasons for discontinuing treatment are listed in Table 4. Nonresponse and adverse systemic reactions accounted for over one-half of all patients who stopped treatment in all 3 treatment groups. Given the 200-mg stepwise dose reduction scheme utilized in this study, only 4% of patients in the group treated with standard WBR without EPO (PEGIFN_WBR) discontinued treatment secondary to anemia. Interestingly, the group treated with standard WBR and EPO had the highest rate of premature dose reductions secondary to adverse events. Across all groups, 6% to 15% of patients discontinued treatment secondary to adverse events after they had become HCV RNA undetectable.

[CockSparrow]

Study Discussion
Discussion
The hypothesis that hematologic growth factors could potentially improve SVR if started at the initiation of HCV therapy is based upon several observations. Over 20% of patients who receive PEGIFN and RVN must either alter the dose, temporarily interrupt, or prematurely discontinue either 1 or both of these medications. 1-3 Previous observations suggested that reducing the dose of PEGIFN or RVN to less than 80% of the cumulative maximal dose that would have been received during the first 12 weeks of treatment was associated with a significant decline in both EVR and SVR.4,5 The use of a hematologic growth factor after patients developed anemia improved serum hemoglobin and allowed patients to remain on either full-dose RVN or to increase the dose in those patients who already required a dose reduction.11-13 In a prospective, double-blind, placebo controlled trial a significantly greater percentage of patients treated with EPO were able to receive 80% or more of their target RVN dose, had a significantly greater cumulative RVN exposure, and reported a significantly better quality of life.12,14 However, none of the previous trials evaluated the impact of the hematologic growth factor on SVR. Despite this, it was widely assumed that the positive effects of utilizing a hematologic growth factor would translate into an SVR advantage; and the routine use of these products during HCV treatment began to proliferate without any data to suggest that this approach would improve outcomes.

Although generally safe, the use of hematologic growth factors has been associated with adverse events, which include hypertension, headache, arthralgias, paresthesias, injection site erythema, thrombosis, thromboembolic events, and antibodymediated pure red cell aplasia.16-19. A recent report has also documented pure red cell aplasia in an HCV patient receiving EPO to treat PEGIFN-induced and RVN-induced hemolytic anemia.20 The use of a hematologic growth factor nearly doubles the medication costs associated with the treatment of HCV.21 Despite this, a recent analysis suggested that the cost of utilizing a hematologic growth factor during HCV treatment was well within the range of other well-accepted medical therapies associated with an increase in quality-adjusted life-expectancy.21 However, such an analysis is predicated upon the assumption that the use of a hematologic growth factor actually enhances SVR; which it has never been demonstrated to do.

The present study was performed to test the hypothesis that the routine use of EPO during HCV treatment would reduce the incidence of PEGIFN-associated and RVN-associated hemolytic anemia, reduce the need to lower the dose of RVN, and enhance SVR. Indeed, initiating EPO at the start of HCV treatment along with PEGIFN and RVN did significantly reduce the incidence of anemia and the need to reduce the dose of RVN. Unfortunately, this approach did not affect either RVR, EVR, or end-of-treatment VR and failed to enhance SVR in patients who received the same starting dose of RVN. In contrast, a significant increase in SVR was observed in those patients who received a higher starting dose of RVN.

The overall rate of EVR, end-of-treatment VR, and SVR for patients treated with standard WBR (800 to 1400 mg/day) in the present study were 65%, 43%, and 24%, respectively. This is somewhat lower than that reported for patients with HCV genotype 1 in several large multicenter, randomized controlled trials.1,2 The reason for this lower rate of VR likely reflects the high percentage of African Americans enrolled in the current study. Overall, 39% of patients enrolled in this study were African Americans, compared to less than 10% in the studies of Manns et al.1 and Fried et al.2 It is now well established that the VR of African Americans with HCV genotype 1 is significantly lower than observed in patients of other races at all times evaluated.22-24 Despite the high percentage of African Americans enrolled in the present study, the SVR rate calculated according to the per-protocol analysis for the control group treated with PEGIFN and WBR in this trial was very similar to that recently reported in a large community-based trial utilizing the same doses of PEGIFN and RVN.25 of PEGIFN and RVN.25

Achieving an SVR in patients with chronic HCV is dependent upon 2 steps: (1) the patient must first respond and becomeHCV RNA undetectable; and (2) the patient must not relapse. The former is primarily dependent upon the antiviral and immunologic affects of interferon. Adding RVN to either interferon or PEGIFN monotherapy enhances VR by about 15%.1,2,26,27 However, the primary role of RVN is to reduce relapse, and in large controlled trials the use of RVN reduced the relapse rate from approximately 50% to under 20%.1,2,26,27 Furthermore, the higher the initial starting dose of RVN, the lower the relapse rate, even though higher doses of RVN were associated with more frequent dose reduction.28,29 A recent study has suggested that dosing RVN by body weight enhances SVR over that observed with an 800 mg/day fixed dosage.25 This is likely the result of providing a higher dose of ribavirin to those patients who weigh more than 65 kg.

The results of the present study are in agreement with these observations. Patients who were randomized to receive the higher dose of RVN (approximately 15.2 mg/kg/day) had a significantly lower relapse rate and higher SVR rate, even though nearly one-third of these patients required dose reduction. Although previous studies suggested that reducing the dose of RVN negatively impacted SVR, more recent studies have demonstrated that dose reduction to even 60% or less of the total cumulative RVN dose does not appear to affect SVR as long as RVN dosing is not temporarily interrupted or prematurely discontinued.7-9 This appears to be especially true in those patients who have already become HCV RNA undetectable prior to dose reduction and in those patients who achieved an RVR and were HCV RNA undetectable within 4 weeks of initiating HCV treatment.6-9 These observations provide an explanation as to why the routine use of EPO did not enhance SVR in the current study. In addition, the dose reduction strategy employed in the current study, reducing RVN by 200 mg increments, limited the number of patients who either interrupted or prematurely discontinued this medication. The results of the present study do not imply that the use of hematologic growth factors should be completely abandoned in HCV patients receiving PEGIFN and RVN. Approximately 10% of such patients experience a profound decline in serum hemoglobin, by 4 g or greater, within several weeks of initiating treatment and must interrupt or stop therapy.30

Severe hemolytic anemia secondary to PEGIFN and RVN therapy is also much more common in patients with cirrhosis awaiting liver transplantation, 31 in patients with recurrent HCV following liver transplantation,32 in patients with hemoglobinopathies, 33 and in those with chronic renal insufficiency.34 It is unlikely that such patients could be successfully treated with PEGIFN and RVN without the use of a hematologic growth factor. Randomized controlled trials in these specific subpopulations are likely to demonstrate that hematologic growth factors will yield an SVR advantage.

[CockSparrow]

Conclusion

Several studies have now demonstrated that higher doses of RVN are more effective at reducing relapse and enhancing SVR.25,28,29 A significant reduction in relapse and increase in SVR were also observed in those patients who received a higher starting dose of RVN along with EPO in the current study. This does not imply that a hematologic growth factor is absolutely necessary to treat patients with higher doses of RVN or is required to enhance SVR with this treatment regimen. These questions were not addressed by the treatment protocol employed by the current study. However, it appears that the starting dose of RVN may be the most important factor associated with reducing relapse and that dose reduction, at least by small amounts, may not alter this relationship. This possibility deserves further investigation.

In summary, the routine use of EPO did not enhance SVR given the same starting dose of PEGIFN and RVN. This suggests that reducing the dose of RVN by 200-mg decrements should be the first response in an HCV patient who develops anemia secondary to PEGIFN and RVN therapy. In contrast, that subset of patients who develops anemia that is so rapid in its onset and severe that it could not be overcome by dose reduction alone could potentially benefit from the use of a hematologic growth factor initiated at the onset of therapy. A randomized controlled trial evaluating this possibility in this specific patient population is clearly needed.

[meki]

This kind of follows the concept that:

If they could hook us up and keep us alive --- to dose the body massively (toxic) for a very short period of time - we could cure faster with more of a guarantee (unless they couldn't keep us alive)

And that Riba is the side that sucks the hemo out of you.

Meki

[CockSparrow]

Thats what the EPO is for. Keep the hgb above anemic levels.
The EPO sides are a little concerning thou
CS

[cruelworld]

i just met with dr. vierling, chief of hepatology at baylor college of medicine houston.
i went to see him to up my riba even higher than 7 a day.(my gastro wouldnt approve any more), my dose is 20 mg/ kg/day (more than the high dose of this study). im tolerating well so far no EPO needed, i did get down to
hemo 10.6 but rebounded back to 11.2 presently. he said he didnt believe anything over the normal dose of 12 to 13 mg/kg/day is worth it or beneficial. i think its mostly a lack of these higher dose studies and the general high toxicity to the average patient that causes his conservative outlook. he cited some study of 4000 patients that is not available to us which convinced him of poor risk to reward ratio. in any case, he said that since im tolorating well,  i could continue and it would be ok. he didnt seem to think the huge SVR benefit was there. his thoughts on this was a big disappointment to me. i will continue sticking with  20 mg/kg/day dosing as i am grabbing at anything that gives me hope and i believe it will eventually be proven to be worthwhile. presently,
i believe that this study is a step in the right direction but again the group size is too small to really turn heads especially when toxicity is considered. it is encouraging to note that this study only raised the dose slightly (from 13 to 15.2) and showed good results. hopefully, one day this approach will be proven to have significant SVR benefit. the others here in the forum on high dose riba appear to be at about the same dosing level as me.  i hope that all of you suffering through high riba dosing,  
are rejoiceing in this relatively insignificant yet good news. i sure am, whew! i am surely, more than ever, a riba raging fool with no help from  ADs. because i have carefully limited my exposure to people  i miracoulously still have a few friends left!  the other key issue of the meet with the big doc was extended treatment.  just as the other top docs are
recommending  36 weeks of UND so did he, which would let me bail out at 58.
i just took shot 36 and will probably push through to 72 against his recommendation.
he said, once again, i can do it but the statistics (in his opinion) dont justify the risk to reward ratio.  instead, ive come up with a compromise. i will probably start a taper off at 58 and reach zero dose at 72. i think i can live with this and feel good about it.

i will say that these 36 weeks have felt like 36 years and im not really sure how i will hang on, but since ive decided i am an invincible warrior i guess ill have to!   i really have been trying to use vertex as an excuse to quit now and hit it later but my sides
are not killing me and the idea of starting over at a later date doesnt appeal to me.
i hope this info helps someone out there in hepper hell.

[zazza]

I was wondering how you are doing. Good to hear you are still hanging in there. I would not mind an extra pill of riba myself, but my doc says no because of the dosing recommendations in my country. I weigh 75 kg and am on 1000 mg riba and 120 mcg PegIntron. My doc has approved the 72 weeks, and he seems determined to keep me on a dosing which will keep me capable of completing the extension without risking to reduce the dose because of bad blood work. I guess I will just have to be satisfied with that.

I upped my interferon last Wednesday because of my weight gain on tx, and have had a pretty rough week because of migraine. I will see on Wednesday if this repeats itself or if it was just one of those bad weeks.

Good luck, fellow warrior! Zazza

[DoubleDose]

If I am correct in interpreting that you became undetected at week 22, and are going to schedule for 58 weeks....then I think your strategy of going to 72 weeks is a NECESSITY.  If you were only initially undetected at 22 weeks, then you are a true late responder, and almost every study in recent years has shown that the 72 weeks benefits this group (late responders) by far the most.  Probably a doubling of SVR rate for this group.  In my opinion, you should NOT dose reduce at all, from 58 to 72 weeks.  This is precisely when you need to keep the same decline curve going, in order to mop up all the undetected, reproducing virus from the blood and hepatocytes.  The high riba is definitely a good idea, and will heavily increase your odds of SVR, as seen in just the study cited above.  The only issue is whether you can continue to tolerate a very high dose of Riba.  If necessary, use EPO as much as the doctors will allow, so that you can maximize this part of your tx.  

By the way, I did 72 weeks, on my second round of tx, after initially relapsing after a 15 month round, and also was undetected late, around week 19 or week 20. ( I am 4 years into SVR!)   Reread the studies on extended tx.  I think you will find the above info. to be pretty much on target.  You specifically are the profile that most needs the 72 week tx length...and at full dosages.  I have no doubts that that regimen will allow you tremendously high odds of SVR.

Good Luck!!

DoubleDose

[katerika]

Are you both Genotype 1? Week 12 VL 19,000 started with 397888*
I am considering pushing for a higher dose of Peg, does that effect the Hemeglobin like the Riba, this week I am at 10.7, and hoping to rebound once again without additional meds. I'm 185 and taking 1200 Riba.
Thanks Teri

[jmjm530]

Didn't wade through it all, but it's been apparent for some time that higher ribavirin doses are associated with higher rates or SVR but also with more side effects. Also previous studies have shown that epo increases SVR by reducing those side effects and therefore allowing patients to continue with treatment full dose. Not sure what fine points Shiffman is making, but reducing riba as first response -- esp early in tx -- seems to go against everything I've read previously. Don't know if he bothered to address these previous studies.

-- Jim

[cruelworld]

zazza,
at least your got you INF increase which i think will help. i predict the increased sides will level out and barely be noticed. as far as riba goes, i wouldnt feel too bad about your dosing especially now that your INF is more. i strongly recommend against this but as you know some posters have used the extra riba that you always get to up their dose without doctor approval. so long as the extra dose is small and you do constant blood work the risk from this is minimized. i do feel like this is a personal life or death struggle and certain risks are acceptable. after all, we are the ones who might face relapse, not our doctors. hang in there!

katerika,
looks like you barely made the minimums to stay in the game, whew! you could certainly use some extra horsepower with those results.  i consider higher INF dosing more risky than extra riba. in the end it all all boils down to tolerability. at least try to increase dosing of something and see if your body can accept it and rebound.
when i was at hemo 10.6 i couldnt really notice it being much different from hemo 12.
i felt crappier but my fatigue was similar. you wont know until you try and your viral
response warrants more aggressive treatment it in my opinion.

double dose,
i love it when a heavily decorated and seriously battle scarred veteran recomends the full battan death march! very encouraging!  i do stop to consider the docs more conservative recommendations and unfortunately outcomes such as yours are the
reasons for it. is it really worth it? it certainly is a big gamble and i vacillate on the issue every day.  would you agree with the theory that permanent sides are more of a function of body type than heavy exposure? it seems than many 24 week people
on standard dose still have as many lingering problems as anyone. i lean toward the idea that your body either can deal with the toxins or not, sort of like russian roulette.
the overexposure may not play as much a role as body type/ genetics. of course
some of this  thought process is folly and has to be wrong. the more poison you take the more it will (could) hurt you. i have gotten my workouts up to 22 mins a day at
heartrate 135. this is my only defense mechanism to not let my system become disabled. it seems to be working. although with each new day the fatigue is still there
but the workout itself truly defeats much of the fatigue (after a rest) for that day.
i suspect that this could help you if you are not already doing this much cardio or more. naturally, there is intense difficulty in getting started on bad days but after about 7 mins of legs and lungs being on fire i level out and do fine. after i finish treatment i plan on reaching my usual workout goals (pre treatment) which are
a daily 45 min cardio burn at heatrate 165. this is a very achievable goal with vast benefits. if you are not already doing this, i encourage you, just as you encouraged me, to go for the full cardio death march. when ive been out of shape before i remember one time where it took me a full year to reach this cardio level and was
painfully discouraged the whole way. i thought i would never make it but i did eventually and was rewarded fantastically. while im on the subject, i finally bought the lance armstrong book and loved it and recommend it to everyone. the irony of the story
to me is the fact that his cancer survival was relatively easy in a way compared to the
uplifting tales of life as a pro cycle racer/warrior. the difficulties he overcame in that arena have given me new strenght to push on. a very uplifting and interesting book.

heres a toast for accomplishment to all the brave dragon slayers.

[DoubleDose]

I am indeed just getting back into the heavy exercise and aerobics routine.  I have been really sporadic in the past three to four years in terms of structuring a real workout rprogram, as I had done for years before tx.  I do agree, that this might help lift me out of some of the 'doldrum' type after effects that I have experienced.  I agree that possibly body type, and also maybe the propensity to autoimmune diseases may determine who has serious post-tx issues more so than tx length.  If you handle the tx smoothly and can continue the workouts, you may be just fine.

  I did recomment the full scale, world-war, no holds barred, guerrila battle plan to you, not only because I had done it myself, but because I relapsed once after being undetected, and for two bigreasons: not enough time after being initially undetected, and not enough Riba.  Also, the studies clearly show that for a late responder, like you and me, your odds of SVR DOUBLE by going the 72 weeks.  Now, don't cheat, and start reducing doses, because the studies were done with constant dosing for 72 weeks, with little or no reductions.  You are clearly in a good position to get the SVR, but DO NOT underestimate the significance of being a late responder, and how difficult it still remains to get the SVR after a late clearance.  I know several people personally who relapsed for just this reason...not going long enough.  One guy I know went for two years on the third go round, after relapsing twice, and finally got the SVR.  Like I have said, I would do it again to get the SVR, EVEN THOUGH I still suffer from a myriad of after effects.  Having the SVR is far more important, in my estimation.  Heck, after awhile, you almost start to LIKE all the interferon!!!!  Kind of a familiar buzz!  I think you will do just fine...just stick to a good, proven plan.

I will take your advice on the exercise issue, because I also think the benefits could be great.  I have allowed some bad habits to develop after SVR, and eating is also one of them.  Weight gains after SVR are very common, and I need to address all of these issues.  Good Luck!

DoubleDose

[jmjm530]

To paraphrase Dr. Afdhal, studies are the cookbook recipes, but it's up to a good clinician to individualize those studies to fit a given patient. I don't know your complete history, including liver damage, but it sounds like your doctor is trying to individualize your treatment based on the current 'cookbook' studies. Keep in mind that the 72-week extended data for those dectec at week 12 used fixed-dosed ribavirin (800 mg) and not weight-based. This was bound to skew the figures somewhat. FWIW my doc -- another big-wig honcho -- also treats between the studies and recommend I treat for 54 weeks which was a variation of Drusano (48 plus week UND) based on my individual stats.

Does this mean you shouldn't treat 72 weeks or go for the max with the riba? Not at all, but just that it's a complex matrix of decisions and you have to take a lot into account, including how much do you have to lose if you don't SVR. In other words, you want to make sure that the rest of you (besides your liver) is left standing in the end. And part of that equation, at least for me, is how much liver damage do you have? If you have significant liver damage, more risks with the tx drugs are warranted. If not, don't go crazy because if all else fails, you can always regroup and treat another day, hopefully with better and shorter drug regimens.

As to my own cookbook, I am more optimistic on ribavirin increases than you doc, if you can tolerate it. Also, not sure about the taper-off, although I did hear similar from a very well-known hepatologist, and indeed it may just be the right compromise. Don't kid yourself that this is a science or that there are magic numbers. In the end, once you get all the info in your head, your guess is as good as anyone's.

All the best,

-- Jim

[cruelworld]

as much as i wish that i had options, my heart says that i really dont and its that simple.

positive factors,
somewhat young 48: good bmi 21: good physical condition: tolerable sides
3.1 log drop at 9 weeks: tolerating high riba well  

negative factors,
stage 3: high viral load, week 20 UND

instead of going another 9 months now i believe that 6 months with vertex later will
get me SVR. this is hypothetically a better deal. as much as i like to procrastinate, im afraid this is not the time to do it. in all reality i may use vanity as my excuse to stay in the game. it will take me forever to grow back my long hair if i do another round!  i hate to be reminded of the uphill nature of my profile but i am very confident of SVR if i do the full monty punishment. double dose may have convinced me to go all out with no compromises. as i near the finish line i probably wont have
the courage to reduce dosage but i will find out. as i say, each day is a day of incessant squirming to find an easy way out the back door. at the end of each such day i always conclude that i have no room to cheat and i must push on with uncompromising ferver. i may even do a month or two of peg every 5 days for a little extra boost. it did break my heart to see the big liver doc
shoot down my aggressive plan to slay the dragon but as you say, this is what they are obligated to do, give you statistical cookbook solutions.
thanks for the measured advice and reassurance as my confidence level is high and rising thanks to the hard work of you and many others around here.
i guess if i can survive another nine months of riba rage without going to prison
ill be ok!  

ps: have you gotten your cardio routine up to speed yet?

around here
the invincible warriors can never be defeated

[debnevada]

i don't know how you do it Cruel. I'm taking 1400 riba and can't do anything more than light housework. I mentioned it before and although i have a pretty high BMI, I was very active last year before i became ill, ran a half marathon and did boxing training for several years, did tae kwon do for a year concurrently, etc.  My counts are not at all terrible. RVR on week 22 on Friday.

How do you do it?

Deb

[cruelworld]

as much as i would like to say its because im good looking, intelligent or empathetic, im afraid i wasnt endowed with much of those qualities. it appears that sheer luck is the great divider. while were on the subject, ill trade you my riba tolerance for your RVR! ( from your post i assume you were UND at week 4, not week 22) correct me if i misunderstood.
believe me, i am still thoroughly terrorized by sides and do attribute some extra tolerance to high heartrate (short sessions) cardio. im guessing that  you are probably dosing higher than i am. my level is 20 mg/kg/day (1400mg a day at 155lbs) and every little bit hurts!  lance armstrong tried to work out too much on his chemo and they had to make him take it easy. he was out riding his bicycle at hemo 7 and tried to climb a hill and had to lay down in someones yard. can you imagine that! hang tough, itll be over in a jiffy.

[cruelworld]

i almost forgot, thanks for finding that study  and bringing it to light. i had given up hope that the medical community would ever pursue a narrowly focused high riba study.
if these positive results keep coming in, maybe SOC may offer more options in the future.

[debnevada]

yep you are taking the same riba as me but weigh less. I'm one of those big ole' strong girls. used to be able to leg press over 300 which isn't bad for an ole' girl.

i said that wrong. I was RVR at week 2 and i'm currently getting ready for week 22.

but i can't even go up the damn steps without getting my heart rate in the 160s and sweating like a pig and breathless

and my counts are great. down to 12 from 16.9 prior to tx and going back up again.

anyway...

[CockSparrow]

Thanks, I was kinda thinking of you when I came across the study.
I found the study interesting for a number of reasons.
1. It studied whether EPO improves SVR when on SOC. It doesn’t.
Jim this is why Shiff recommends dose reduction.
I think that patient selection in this arm may have skewed the results a bit thou.
Strange that the previous studies on EPO only looked at adherance and didnt bother with SVR.

2. Increasing the Riba dose made one hell of a difference to the relapse rate.
Especially as the Increase in RBV wasn’t that great.

3. Increased Riba made no difference to the VR during Tx, only to the relapse rate.
This surprised me a bit.

I guess that for those of us that are difficult to treat then maybe we should consider High Dose PegIFN to increase VR and High Dose Riba and lenghtening Tx to reduce relapse.
Pleasant thought ay.

BTW I think that the Sx experienced on Tx have a lot to do with the symptoms we have b4 we start Tx.
CS

[cruelworld]

my original plan was to go even higher with riba dosing and use EPO as i am sure
i would need it to get dosing higher. i at least wanted to get to 8 a day with the goal of 10 (28mg/kg/day). two docs have turned me down so far and in the meantime i sort of chickened out on the idea of having to use the powerful growth hormone to get there. we simply dont have enough proof of high dose riba efficacy to justify a voluntary use of rescue drugs (for me anyway). now, youve uncovered this study to suggest that even a small increase gives great results. another small step towards
higher SVR rates.
i have found my personal sweet spot for riba tolerance and will remain on this dosing.
it will be interesting if future large studies prove what the swedish pilot study suggests - super super high riba dosing gives unheard of SVR rates (90% for type 1)
we may very well have a great cure right under our noses and not know it.
i think the anemic toxicity of riba is a road that doctors and pharm companies dont want to go down and represents the real stumbling block for future research.
if  the new drugs dont do as well as expected then i think we will see this avenue explored more thoroughly.
your last thought about pre tx symptoms being a positive predictor of tx sx sort of applies to me but not really. i was 1000% healthy when i was diagnosed and
always have been (thank god for the small favors) but my sx have been pretty rough.
the correlation makes common sense but my thinking says that once you become UND some symptoms should , could, and would disappear. what do the docs say on this issue? do you know? this pre to tx sx predictor correlation would be hard to track but i will carefully try to notice this from now on within the population here.

uh oh, i sense my dragons becoming restless, i better go grab another handful of
riba rage and lock myself in the house!!

[CockSparrow]

I wasnt saying that feeling 100% b4 Tx improves SVR, in my case that would be a negative predictor. Just that less sides are experienced, maybe. Well that applies to me at least.
I think you would still feel like **** if anemic, but EPO would improve QOL, if nothing else.

This is the 2nd study i have come across that states that RBV 15 mg/kg/day reduces relapse. The other was a Taiwanese G2 16 week study using WBR and Pegasys that had SVR rates 15% or so higher than Accelerate achieved with G2s. It achieved 77% SVR with non RVR. One of the reasons they gave for the high SVR rates was the lower body weight and there higher mean RBV dose. Seems like 15 mg/kg/day RBV reduces relapse across genos. Pity it tends to make you anemic.

Yeh i had also come to the conclusion that just as the new drugs get released we will have finally worked out how to use the current ones more effectively. This is a good thing as neither of them will be replaced any time soon. With the way the drugs i liked the sound of keep falling by the wayside VX-950 better work on G3s or I'll stuck with the current two. Might have to catch Giiarda so i can lay my hands on Alinia.

All the Best
CS

[jmjm530]

Cruel:nstead of going another 9 months now i believe that 6 months with vertex later will get me SVR. this is hypothetically a better deal. as much as i like to procrastinate, im afraid this is not the time to do it
----------------------------------------------
I didn't bring up the Vertex option, but as long as you did, yes, it's certainly an option these days for a slow responder.

Of course, check my figures with both the studies and your doctors -- but if you extend for 72 weeks, you will have around a 50% chance of SVR given your slow response. On the other hand, if you treat for 24 weeks with Teleprevir, you should have around an 80% chance of SVR, if the stats for relapsers turn out to be the same as what appears to be happening in the tx naive 24-week arm. Lots of if's and buts, I know. No easy decisions. BTW I wasn't suggesting your doctor was following the "cookbook", quite the contrary. His suggestion to treat somewhere between 48 and 72 weeks was an attempt at individualizing your treatment. I think what both he and I are concerned about is weighing the risks of such an agressive approach against whatever incremental rewards there might be with SVR. Having treated myself -- I double-dosed and did high-dose riba in the beginning -- I understand that we often have to put blinders on when we treat to forge through. But eventually treatment is over and then we do have to reap what we sow. A good doctor is there to remind you of this and make sure you don't do too much harm to yourself.

Good luck however you proceed. And yes, my cardio program has been in full swing, and while I'm sure it's doing the ticker some good,  I haven't seen the effects on bp and bmi that I would have liked.

All the best,

-- Jim

[jmjm530]

Still not convinced that lowering the riba is the right first move. Maybe with the study population and does in that particular study, but too much previous stuff suggested the avantantages of epo.

As far as very high-dose ribavirin (VHDR) per the Swedish pilot study -- I also wondered why no follow-up research here given their extraordinary 90% SVR rate. (I was so gung-ho about it, that I actually tried to emulate the study myself but ended up in the ER at week 2-3 of tx -- although looking back, I did ramp up the riba too fast, even by their standards).

I think the reason why we will never see this avenue fully explored can be found in Dr. Afdhal's remarks in the Q&A following the "Who Moved My Peg" presentation at the Clinical Channels web site -- a presenttion which I recommend in it's entirety. http://www.clinicianschannel.com/

First he starts out saying how spectacular the results were, but then he drops the other shoe and basically says it ain't going to work here because patients won't tolerate that tough a treatment. They want their life, they want to work etc etc.. I believe he uses the words "efficacy at the expense of tolerability" or something like that.

Personally, I wish at least some follow-up on those studies had been done, perhaps as an option for those willing to trade tolerability for efficacy. What's interesting, is that my understanding is that the Swedish researchers think that VHDR is the lesser of two evils when compared to extending SOC beyond 48 weeks because of the increased exposure to interferon. Yet here, no one seems to blink anymore at 72 weeks of interferon.

-- Jim

[cruelworld]

i hate to drag this out any more but my last question to you is this. if you were in my shoes what would you do?  assume that i will have post tx exposure problems
just exactly the same as yours.  imagine that you have my profile and consider only your perspective on treatment as you know it.  these are the basic five choices

1. quit now at 36 weeks and wait for vertex  
2. quit at 48 weeks  
3.quit at UND plus 36 weeks which would be 56 weeks  
4. quit at  UND plus 48 which would be 68 weeks    
5. quit at 72

also in this process a while back i did contact dr lindahl and got her email address.
i told her my gastro doc would be contacting her but the study was too small and he just refered me to dr. vierling at baylor. this is her address:  karin.***@****. you had some questions for her and she is available, see what the latest news is.

[gauf]

Let's talk about tolerability. I plan to double dose Peg and up the Riba. I hear that there are dangers. What, specifically are the dangers of anemia besides fatigue? What if procrit was was administered prior to tox? Can we get proactive on this regimen?  And what are the long term effects of severe anemia?

[DoubleDose]

I'll just add my two cents as well:  

1. Why throw out 36 weeks of hard fought tx, to wait for something that might also call for 24 to 36 weeks of concurrent interferon dosing?  Just do another 36 weeks from today, and you have finished the full extended protocol.

2.  I would suggest numbers 4 or 5, for the best odds, right now, rather than good odds several years from now.  You are on your way to success, and have acclimated pretty well to the meds.  Why start over.

3.  Number 2, quitting at 48 weeks, is not a good choice at all.  You will be still doing additional tx time from today, and will almost certainly relapse, from a statistical standpoint.  Choice #3 is hardly any better, and still leaves you having done a 'partial tx', with lots of effort and time, and leaving you with very little odds for SVR.

From my perspective its a great opportunity for you to beat this virus, NOW, and in just 36 more weeks.  Quitting and starting over, with the significant progress you have made to date, does not really sound like the best plan to me, since you will eventually have to do the interferon again, along with the vertex, and possibly for as much as the 36 weeks that it would take you right now, to get your SVR.  

I didn't mean to butt in, but I couldn't resist.

DD  

[jmjm530]

Choices. Choices. Choices. :) I do agree with DD that #2 doesn't offer very good odds, so let's nix that one.

Just so I don't confuse things, could you please recap all your stats again, including:
Age, Sex, Race, stage of fibrosis, height, weight before tx, current weight, hgb pre tx, current hgb, current ANC, dose of peg and riba, any dose varitaions or reductions, any helper drugs (Procrit/Neupogen), pre-tx viral load, PCR history during treatment including test results, test sensitivities; side effects during tx, other health issues, first treatment for HCV or have you treated before? And anything else you might think important for your profile.

[jmjm530]

Also how long do you think you've been infected.

[jmjm530]

While waiting for your reply, I'll play devil's advocate with some of DD's thoughts -- and even devli's advocate with some of my own thoughts -- not so much to rebut them, but to help point out what I consider to be the complexities of making this kind of decision.

DD:  Why throw out 36 weeks of hard fought tx, to wait for something that might also call for 24 to 36 weeks of concurrent interferon dosing?  Just do another 36 weeks from today, and you have finished the full extended protocol.
------------------------------------------------------------------------------------------
If you stop now and then do 24 weeks of Telaprevir protocol, you will have treated a total of 60 weeks with perhaps an 80% chance of SVR. If you extend to 72 weeks, you will have treated of course a total of 72 weeks which what appears to be a 40% chance of SVR according to Berg if memory serves me. So that means double the chance of SVR with the stop and Telaprevir approach with less time treating.

However, on the other side of the coin, the extended tx studies used fixed-dose ribavirin (800mg) so perhaps the 40% SVR rate has been understimated. In the same breath, perhaps the 72 weeks has been overestimated. Also, if you stop now there is no guarantee you will get into a Telaprevir trial right away, and what if something happens and it doesn't reach market in a couple of years?

Also, even though very promising, final data still isn't in on the 24 week group and lastly, will previous slow responders match the 80% SVR rate that the tx naive groups seems to be achieving. The other thing is that you are already treating and stopping and then re-starting is probably not the easiest thing to incorporate into your life.

[DoubleDose]

I agree with your 'devil's advocate' comments.  There are many 'unknowns' and variables in this decision.  You have pointed out the real pros and cons, as well as the fuzzy areas.  I really do believe that someone on high dose riba, who has been undetected since week 20 or so, and who stays undetected to the final 72 weeks, at full dosing, has a much higher odds of SVR than 40%.  I remember my doc telling me that 80% was more likely the real odds in my case, and my situation was somewhat similar to this one.  With the pedal to the metal for just another 36 weeks, I think that the odds of success in this case are pretty compelling.  You present just about every issue that might be a factor, and your analysis should be a good foundation for reaching a decision.

DD

[cruelworld]

the inglorious stats of cruelworld

race and gender,    dirty white boy
age,                             48
height                           6,0
weight pre tx                175     BMI  23.7
weight now                157    BMI  21.3

body state pre tx      healthy, strong, good shape
symptoms pre tx      asymptomatic
medical history        normal childhood illnesses, tonsils taken out,
                                  mild hypertension taking atenenolol  for 1 year
                                  unremarkable otherwise
liver histology           stage 3 grade3  
                                  septal fibrosis noted  (bridging not mentioned)
                                  no cirrhosis

rescue drugs            none

hgb pre tx                  15.9
hgb 3rd  week           12.8  (highest during tx)
hgb avg  on tx            11.7
hgb  now                    11.2
hgb lowest                 10.6   (riba induction)
anc current                 2313
all other bloodwork      good - if out of range, only slightly so

INF dosing                  pegintron 120 mg  (centered on weight based chart)
                                                                       100% compliance no variation  
riba dosing                 week 1 - 19        1000mg  (at bottom cusp of weight chart)            
                                    week 20-26         1200mg  
                                    week 26 - 36       1400mg

infection maturity       30 years
pre tx viral                1,630,000 iu                                           ast 127    alt 206
week 9                              1280 iu           (3.1 log drop)                138        192
week 18                                 89 iu                                                  103        142
week  19                               >5 iu     heptimax

week    27                              >5 iu     heptimax                                 72        93
week    34                              >5 iu     heptimax                                 89      105

viral curve                        interpolated to .3 log per week

sx                                      all the normal stuff
                                          middle of the road severity
                                          can work a week at a time here and there
                                          riba induction pretty hard but stable now and better

treatment status       naive



double dose,
i certainly didnt mean to "2nd rate" your opinion (compared to jim). its just that he never really gave me any really clear recommendation as you emphatically and specifically have. now that i read  yalls comments i realize that this argument boils down to predicted SVR rates for each choice. on the 72 option, your guess of 80% SVR rate may be a little overestimated but maybe not. it does help (in my mind) that your doc suggested this number. very persuasive.

jim,
i believe that double dose's opinion  could be characterized as "youve got a good shot if you go all out to 72, go ahead and get this overwith and be prepared for the risks of heavy INF exposure"  
you on the other hand, you  appear to be more cautious in regards to exposure
and this is the reason  for the need of your possibly contrasting opinion.
i included everything i could think of. my personal input is this, i can easily
make 72 but i do harbour fears of exposure and as a personal choice im not
all that prepared to live with permanent sides. as far as vertex goes i will
not accept a trial with dead arms, so i will have to wait for FDA and this requires a
"worst case scenario outlook". i do think that because im asympomatic and
healthy i could hang on safely for a few years. also i still have the option
to go for very high riba dosing as this was my intention. its just been delayed because i havent found the right doc yet. the liverhead talked me out of it
and maybe i should reconsider?

[cruelworld]

remember, rather than choices i really want to know  -
what single choice would you make "if it were you'

[DoubleDose]

Here's one final suggestion:  Speak with one or two prominent HCV docs and describe your situation (you might e-mail them).  Most of the major docs out there have confronted cases like yours many times, and know all the ifs, ands, and buts regarding the various options you describe.  I think that getting some really qualified input would make your decision easier, and provide some 'expert' opinion tailored to your specific situation.  

Also, sometimes you just need to 'grit things out' for a few weeks when going through a period of uncertainty or confusion.  Often the right solution for you will make itself obvious, and you will feel it from within.  Right now you are forcing the issue a bit, and maybe prematurely.]

DD

[CockSparrow]

DoubleDose’s 80% figure would be close to the mark, your chances maybe even higher.
The article below produced 77% SVR with 72 weeks for G1 slow responders. http://www.natap.org/2006/AASLD/AASLD_34.htm.
This was Per Protocol whereas Bergs was ITT with 800 mg RBV.
It also discusses shortening Tx for G1&4s who RVR.

Add this to the Study above and your SVR chance could well be higher, so long as you remain UND and don’t need to dose reduce the RBV too much.

You asked Jim what he would do in your situation. I know what I would do, and that’s Go all out now. I am in total agreement with DD on this. Why wait when you can kill it with the drugs you are already taking.

Just my view
CS

[cruelworld]

can i come live with yall if i end up with permanent riba rage, brain fog and fatigue?
being the consumate diplomats that you are, you both will probably say yes!
touche! thats the one great thing about this experience, we all become brothers and sisters for life. what a fraternity. does anyone know a 72 person without long lasting battle scars? its an interesting question that i dont know the answer to.

dd
i do need more pro opinions at this point, but anymore i dont even trust the docs on the issues of permanent problems. i think ive seroconverted from riba rage to riba paranoia! its driving me nuts! the funny thing is, my treatment is going easier and better than ever. i made another 22 min skating session last night and i still feel
energized 12 hours later. im running around right now doing housework. what a basket case i have become.

[jmjm530]

Maybe I'm reading it wrong, but for me the study seems to suggest that only EVRs benefit from extending treament to 72 weeks and not those in the non-EVR population who were >50 at week 12 but were not EVR.

From the treatment alogorithm:
----------------------------------------------------------------------------------
- patients with an EVR but with HCV RNA >50 IU/mL at week 12 could benefit from a longer treatment duration of 72 weeks
- consistent with treatment guidelines,[1] patients without an EVR should not continue treatment as the likelihood of achieving an SVR is minimal (2 log drop by week 12 but viremia >50 IU/ml. At least I *think* this is how they define it.

So the question here -- assuming my take is correct -- is if "Cruel" had >2 log drop by week 12, i.e if he was EVR. If not, then the "77%" figure you quote is not relevant at all.

Lastly, later in the paper there seems to be some sort of typo where "350" should read ">50". This occurs a few times.

Certainly hope I'm wrong here.

-- Jim

[jmjm530]

Just to clarify a little. "EVR" appears to be defined by the authors (see chart) as a >2 log drop by week 12, but viremia >50 IU/ml. Hopefully "Cruel" will get back to us with his viral load results both pre-treatment and at week 12.

[jmjm530]

Well, I guess my own question is answered in the title of the study LOL which I apparently didn't read:

Title Study:

72 Weeks Pegasys/RBV in Genotype 1 Improves SVR Rate For Patients With Early Viral Response (2 log reduction at wk 12) But HCV RNA >50 IU/mL
------------------------------------------------
So, yes, per this study, extending to 72 weeks is only recommended if you have a two-log drop by week 12. If you do not have a two log drop by week 12, this particular study appears to offer less hope than Berg, for example.

[cruelworld]

my stats are about 8 posts up

[DoubleDose]

I think cruelworld did have a 3.1 log drop by week 9, which puts him in a VERY strong statistical position to get the SVR in a 72 week course of tx, I believe.  I would bet that with the 3.1 log drop, and with the above standard Riba dosing that his real odds of SVR would be over 90%.  Just an educated guess.

DD

[jmjm530]

Hopefully "Cruel" did have at least a two-log drop by week 12, but I couldn't find his post on that. That does appear to be key, at least by this study.

As to "90%" chance of SVR, I think that very optimistic.

I was given around a 75% chance of SVR with an RVR* (not EVR) and 54 weeks of treatment. Still, 77% is a very encouraging number, and if it turns out that he fits the studies criteria, my suggestion would be for him to print the study out and discuss with his doctor who is head of Hepatology of Baylor. At least that would be my next step.

* Almost two-log drop at week 1; two-log drop at week 2: UND to <50 at week 6.

-- Jim

[cruelworld]

he inglorious stats of cruelworld

race and gender,    dirty white boy
age,                             48
height                           6,0
weight pre tx                175     BMI  23.7
weight now                157    BMI  21.3

body state pre tx      healthy, strong, good shape
symptoms pre tx      asymptomatic
medical history        normal childhood illnesses, tonsils taken out,
                                  mild hypertension taking atenenolol  for 1 year
                                  unremarkable otherwise
liver histology           stage 3 grade3  
                                  septal fibrosis noted  (bridging not mentioned)
                                  no cirrhosis

rescue drugs            none

hgb pre tx                  15.9
hgb 3rd  week           12.8  (highest during tx)
hgb avg  on tx            11.7
hgb  now                    11.2
hgb lowest                 10.6   (riba induction)
anc current                 2313
all other bloodwork      good - if out of range, only slightly so

INF dosing                  pegintron 120 mg  (centered on weight based chart)
                                                                       100% compliance no variation  
riba dosing                 week 1 - 19        1000mg  (at bottom cusp of weight chart)            
                                    week 20-26         1200mg  
                                    week 26 - 36       1400mg

infection maturity       30 years
pre tx viral                1,630,000 iu                                           ast 127    alt 206
week 9                              1280 iu           (3.1 log drop)                138        192
week 18                                 89 iu                                                  103        142
week  19                               >5 iu     heptimax

week    27                              >5 iu     heptimax                                 72        93
week    34                              >5 iu     heptimax                                 89      105

viral curve                        interpolated to .3 log per week

sx                                      all the normal stuff
                                          middle of the road severity
                                          can work a week at a time here and there
                                          riba induction pretty hard but stable now and better

treatment status       naive



remember, rather than choices i really want to know  -
what single choice would you make "if it were you"

[jmjm530]

Cruel: Remember, rather than choices i really want to know  -
what single choice would you make "if it were you"
-----------------------
LOL. You're talking to someone who agonized for weeks -- and spoke to 4-5 top-dog hepatologists -- re whether to stop at week 48 or extend (I ended up doing 54 weeks), and you want a *single* choice :) Anyway, I'll do my best to answer, but maybe not what you want. Probably not what you want :)

First, you had a very nice drop at week 9 (3.1 log). I'm assuming you did not test at week 12, but wonder why your major league doc didn't do that test? Anyway, week 18 showed very little virus and you were UND at week 19. One might even ponder the fact that the week 18 test was a false positive, or some sort of intermittent thing, but certainly can't rely on it. Still, I can why given your week 9 drop, your doc might consider extending, but less than 72 weeks. Keep in mind that studies using fixed dose riba cut two ways. Yes, they suggest you might have a better chance of SVR with 72 weeks on weight-base dose, but they also suggest you may not need 72 weeks on weight-based.

What would I do? Here's how I would most probably handle it, based on what I did myself.

First, I'd order up FULL-TEXT copies of all the extended tx studies, including Berg, the one just posted here, and any others. Then after studying them yourself, I'd make an appointment and review them with your doc. Where I would want to come out of that meeting is your doc's estimation of your chance of SVR with 72 weeks of treatment versus 56 or 68 weeks you mentioned earlier. And if he sticks to his guns -- less than 72 weeks -- then querry him why less, and based on what, given the 72 week studies. You don't just want his opinion, you want his logic, his reasoning.  I would then repeat the same process if at least two other well-respected hepatologists who do a lot of trials -- someone like Schiff, Afdahl, Dieterich, Jacobsen, etc. At that point, hopefully there will be a consensus, or at least things will start getting clearer. That's what I would do because that is similar to what I did.

My guess is that you will get opinions ranging from 56 to 72 weeks -- the 72 week number because it's become sort of a conservative standard for slow responders (Im pretty sure my tx doc would recc 72 weeks in your case) and the lesser numbers based on your excellent week 8 response which brings up the possibity of a false positive at week 18, since you were UND at week 19.

As to the Vertex thing -- first, I'd try and figure out as best I can what my odds will be with extended tx, per some expert opinions. Unless the consensus was below 50%, stopping now and hopping on the Teleprevir bandwagon at a latter date is certainly an option, but not one I think you'll find too many doctors recommending, and probably for good reasons -- some of which I mentioned earlier.

Hope this helps a little.

-- Jim

[jmjm530]

OK. I'll go out on a limb. Factoring in the fact your 3.1 log drop at week 9, etc --
My guess is that the 'magic' number for you is between 60-68 weeks.  (The average of which (64) coincidently is right smack in the middle of your doctor's suggestion (54 weeks and the 72 weeks the studies are based on.).

If you feel any better treating "72" weeks because someone doing a study picked that number, by all means go ahead, but if you're not cured by 60-68, what makes you think you will be cured with 72. Certainly no studies on that one.

I would still follow my suggestions in the above post, at least if you're as compulsive about treatment as I was. It will also give you something to keep yourself occupied :)

BTW I have a feeling you will beat this thing.

All the best,

-- Jim

[DoubleDose]

To put it bluntly:

Its time to suck it up and ride that train all the way into the station.  That's Stop #72.  If you are forced to get off early, say at Stop #64 or #66, you may still be allright, and able to limp into the big SVR terminal.  Its a crapshoot as you clearly can see by now.  The willingness to keep riding is the biggest trick.

DD

[jmjm530]

Just want to add that if you decide to extend, I'd watch your hemoglobin carefully as well as monitoring how you feel. If it drops much more and/or you start feeling worse, I wouldn't hesitate to either drop back down toward weight based (1200?) or add Procrit (epo). In the past I'd advocate adding the Procrit, but not so sure anymore, especially later in treatment. The very high dose ribavirin studies used epo liberally throughout tx but those doses were well beyond what you're on. Also, not sure adding more Peg or moving the shots closer together is such a hot idea either. Maybe just the last month. Dunno. I thought about it myself but ended up finishing on a standard dose. A lot I would think depends on how you're handling side effects. Just remember that there is a lot of life after treatment and you want to arrive there in as good a condition as possible. Sometimes we lose track of this when in the heat of battle (treatment) but doctors are well aware of this fact and therefore most will not advocate too agressive dosing in most cases, unless the patient forcefully advocates it. I know I did in the beginning of my treatment, and I did get myself into trouble. Looking back, not sure all the xtra meds helped my case.

-- Jim

-- Jim

[cruelworld]

thanks for all the help, i owe yall one. when i get rich and famous (a very high possibility LOL!)  ill pay and we will all gang up somewhere and terrorize some unsuspecting town for a few days. we can exchange some exaggerated sx war stories, embarrass some girls and maybe even get thrown in jail. sounds like fun eh?

jim, i started with my hometown gastro and only just met with the liverhead once 2 weeks ago. this is why pcrs were scarce. i feel better hearing that you agonized for weeks over this issue just as i am. i guess everyone does.

i am much relaxed to get you alls opinions. it has helped me immeasurably. i am setting up the big boy meets as soon as possible. once i can get comfortable with a decision, all thats left is doin the time. relatively easy. a big question for the liverheads is recovery time and permanent sx for 72 death march people.  will they even tell me the truth on this? do they actually know the truth?  i hope so.
thanks again and i wish all to have a happy and fatigue free day!
over and out
cruelworld

[jmjm530]

Cruel: will they even tell me the truth on this? do they actually know the truth?

No,.

Cruel: will they even tell me the truth on this? do they actually know the truth?

No.

Cruel: ill pay and we will all gang up somewhere and terrorize some unsuspecting town for a few days. we can exchange some exaggerated sx war stories, embarrass some girls and maybe even get thrown in jail. sounds like fun eh?

Yes.