1b - Slow Response

[miked]

Today I received my results from a week 24 PCR.  I remain HCV RNA posititve with 5,000 IU/mL.

The good news is that I have lowered my viral count from 3,080,000 IU/mL at the start of tx to 9,000 at week 12 and now at 5,000 at week 24.

My doc wants to keep me on tx and monitor for undectable HCV RNA.  Then stay on tx for 36 weeks after undetectable.

Question 1:  "Will I get to undetectable?"
Question 2:  "What are my chances for a SVR?"

Thanks,

Mike

[miked]

Bob, at what point did you actually clear?  Also are you now completed with tx and SVR?

DoubleDose has shared some experience with increased dosage.  I would like to know if you stayed on the same dosage and if it was PEG-Intron.  

Thanks,  Mike.

[miked]

Thanks DD.

[DoubleDose]

If I were in your situation I would make sure to connect directly with your doctor, explain your take on the situation, and then PUSH as hard as possible for at least ONE MONTH of increased dosage Peg...OR being allowed to go to a 6 Day, or 5 day schedule, for a month, with a PCR to determine whether you are undetected.  If you can get undetected, YOU DO have a good shot at eradication....you are just going to have to maintain the higher dose that gets you to undetected, and go for a long, long time.(At least a year AFTER the undetected)  Getting undetected, and staying undetected is PRIORITY #1 at this point.  People with various types of cancer often take much higher doses of interferon, and for longer periods of time, often two or more years.  Impress on your doctor your adament feelings about salvaging THIS therapy!  Ask him not to wimp out!!  IF you are handling the sides up to this point, there should be no reason why he could not allow an incremental increase of 20% or so. Ask him to just monitor you closely.  I did a much higher dose than prescribed, and it worked.  TALK WITH YOUR DOCTOR!!!!!

DoubleDose

[miked]

I'm really frustrated right now and don't know what to do.  Today the PA for my doc returned my call...I had called to ask if there is some way to increase my dosage of PEG-Intron. She said that it was an off-label application and most likely will not be supported.  Additionally she painted a pretty bleak outcome for a 1b who is still detectable at 26 weeks of tx, even though I started at  3 million and dropped to 5,000. Am I kidding myself here or should I accept the fact that I may not be cured.  Sorry to beat this horse some more.  Mike.

[DoubleDose]

My biggest concern in your case is the 12 week vs. 24 week viral load count, which is virtually 'flat'.  Same log-load level.  Maybe the inf. will once again kick-in, and drop the load to undetected, but it seems pretty 'iffy'.  Generally, over a 12 week period, you would expect a continued steep decline, or close to it...like your first twelve weeks.  This is somewhat uncharted territory, since there is not a lot of related data on this particular phenomenon.  It probably will not hurt to wait three to five weeks to see what is going on, because either you will be finally at the undetectable point, OR if you are not, then it will be completely obvious that you need to really push the envelope, to salvage this treatment regime.  Better, I believe, than starting again.  If the load begins to significantly RISE on your Dec. PCR, then I think you may have a bigger problem, and may need a whole new protocol.  If the load stays close to the same, or goes down by just a few thousand, then I think tweaking upward MAY be very helpful.  If you are undetected, then you may be fine with just a continuation of the current dosing, and going for as long as humanly possible, after the PCR.  (12 months or ideally longer)  After the Dec. PCR you might want to really get into the trenches with your doc, and wrestle out a better strategy if you remain detected above a few hundred IU or so.  Tell your doctor that you are not a research study, but a guy who wants to be 'cured' THIS TIME AROUND!
Best wishes...keep us posted!!!  DD

[miked]

The RediPen is limited to .5ml unfortunately.  

My doc said no to dosing 2x/week.  His plan is to continue on treatment with monthly PCRs until undetectable (or levels off or worse elevates).  My next PCR is December 22nd with results lagging 10 days later.

This doc is young and smart but I feel like I'm a bit of a science fair experiment.  Before 2004 AASL he was negative on tx longer than 48 weeks for geno 1's.  Now he's coaching me to stay the course; continue to lower the viral load and then go for extended tx.

Any ideas about just waiting for the December PCR results....if still detectable then ask....or fudge the dosing now to every six days?  There's about a week-10 days of play because I delayed my start date.

Great nickname!  I hope mine will be something like SVR-Man.  Thanks again for your help.  Mike.

[DoubleDose]

How many ml. are there in total within the 150 mcg. Redipen?
If you are using the 150 mcg. / .5 ml, are there one or two additional ml. of fluid left over in the pen, after you do the .5 ml???  Can you use the full amount within the pen??

If so, your problem is easily addressed.  If you are limited to ONLY the .5 ml amount, then you may need to go to a more frequent dosing schedule, like 6 days.  Since you are CLOSE to clearing, you MAY clear on the current dose...BUT..the decline curve is not a very quick or steep one, and in my thinking, this just means an even longer extension after your initial undetected, IF you get undetected.  You may need more than a year of tx AFTER obtaining your initial undetected result.  
Again, you are close to the guideline, so any 'tweaking' upward in dosing should be helpful.  Also, the extended part, after clearing, WILL BE critical to your long term success, I believe.  The slow response chiefly means that your body is killing off HCV virions only slightly faster than it is reproducing them...which means a LONGER time to total ERADICATION throughout the blood and liver.  Getting 'undetected' is only a first step, and getting every virion takes much, much, longer...especially with 1-B's.

Please discuss this with lots of 'vigor' with your doctor.  No sense doing almost enough drug, for almost enough time, and then relapsing....only to have to treat again, with a longer and/or higher dose. If the TOTAL fluid in the pen is ONLY .5 ml. then you will have to get your doc onboard, in order to 'up' the bloodlevels of Peg.  My Peg-Intron vials usually allowed me to get at least .7 ml. and often .8 ml. from them.  I also used the 150 mcg. dosage.  My weight was usually in the high 160's during tx, which is why, when using .8 ml, I was actually getting about 230 to 240 mcg. of PEG, and based on my body weight that was about 3 mcg/kg.  (or 240 mcg.Peg to 80 kg. weight..or 3 to 1)
Hence my nickname: DoubleDose!  Just for the record.

[DoubleDose]

Yes, I think every six days will boost the actual dosing or blood levels, and you can do the math to see what the daily increase would work out to be....but as you indicate, at some point you get behind in your meds, and your doc or insurance is providing meds based on the original weekly schedule.  THAT is why I did the HIGHER dosing, AND drained every 'molecule' from each vial, but still only did the weekly  or standard 7-day shot dosing.  What size vial are you using, and do you use the entire amount from every vial.  Some docs will have a patient use only .4, or .5, or .6 ml. out of a vial depending on their weight.  Often you can get more from the prepared vial than you are prescribed.  Many patients use the entire vial, to boost the mcg./kg. ratio.  It sounds like you may need that boost.  TOO LITTLE interferon can be a cause of failure to fully clear in tx.  The only way to see if that is a possible factor in your 'slow' response is to bump to a higher dose.  I used the largest of the Peg-Intron vial sizes available on my tx.  I am not sure if they have gone to pre-mixed, or more controlled dosing with Peg-Intron in the last 15 months, since I finished tx, but my version was a powder filled vial, that needed to have saline injected into the vial to mix the final solution for injection.  There were several sizes available for the powder filled vial.  Again, I used the largest size available.  

My doc ALSO extended my tx from 48 weeks to 72 weeks since I was a slow responder.  I was still detected at 18 weeks, but was fully undetected by week 24.  I think extending tx was the ONLY way to go, in my case.  I am sure I would have relapsed without the 18 month tx.  You probably need both the bump up in dosing, AND most definitely the extended dosing period.  YOU ONLY want to do this regime ONE TIME!!!!

Doubledose

[miked]

My doc prescribed the "RediPen" which is a device that premixes the Interferon.  

The RediPen comes available in 50, 80, 120 and 150ug per 0.5 ml.  I'm taking the maximum 150ug.

http://www.redipen.com/pegintron/redipen/index.html

The topic of twice weekly injections came up at my last appointment and he was negative on the idea.

Three questions:
1.) Stay at 150ug with monthly PCRs looking for undetectable?
2.) Am I missing an opportunity to kill the virus and go undetectable with above strategy (question #1 that is)?
3.) Move up the injection date to every 6 days on my own and deal with the issues later?

Thanks for your input.  Mike.

[DoubleDose]

Regarding my previous comments, and your dosing info:

I did the larger vial size of Peg-Intron, which worked out to about 2.7 mcg./kg for my weight (180 lbs).  I always TOTALLY drained the vial, using all  of the .7 mg, rather than the .4 to .5 mg. prescribed. My doc had also ordered the largest vial size available, since he seemed to think that a heavier dose would be helpful in my case (though he tried to not admit directly that this was his strategy).  There may be a fear of liability in prescribing larger than normal dosages, but many docs seem to do it anyway.  Using either more Peg-Intron, or doing the dose more frequently, MAY increase your clearance rate, and allow you to first get undetected, and long-term, may allow you to fully eradicate the virus.  I would really discuss this strategy with your doctor, and you may need to be persuasive.  Check out Dr. Ben Cecil's website for some additional medical insights related to customized dosing.

Best of Luck!!!!

Doubledose

[miked]

My doc initially would not entertain more than 48 weeks however with good data he's OK'd me to go past 48 weeks assuming all goes well.  What do you think of the idea about taking my Intron every 6 days....won't insurance or my doc notice?  Thanks.  Mike.

[cuteus]

check Dr. Cecil's site that I gave you above, he is using customized dosages, you can also email him(it might be a while before he answers so email asap)and explain your stats to him.

He had suggested to me to follow the course stated by doubledose.
you can go to hepatitisdoctor.com and print what he has to say on this.
The high iron might have hindered your viral response so far. I would go longer than 36 wks. Dr. cecil mentions this also, check his site and arm yourself with studies and such. The latest Conference(AASLD) in Boston had some presentations on changing doses to stimulate a viral response.  Maybe you can do a search on the conference and read the studies presented.

[miked]

I'm taking 1200 mg of Rebetol daily and the PEG-Intron is the Alpha 2b.  Any ideas on how to get my doc to approve an increase in PEG (or frequency)?  I feel that I'm at a critical point right now and don't want to miss an opportunity to kill the HCV.  Once again thanks for your input.  Mike.

[miked]

Wow....thanks for your responses!!!  I'm new to this site and the knowledge base here is impressive.

Below are my stats:
1.) I'm on Peg-Intron at the maximum dose of 1.5 ug/kg.
2.) Additionally taking Rebetol at 1200 mg/daily.
3.) 6'3", 185 lbs. (200 lbs. @ start of tx).
4.) Genotype 1b.  
5.) I've never been treated before.
6.) Estimated 20 years for infection.
7.) All labs for blood work are great (red,white,Neutrophil)
8.) ALT/AST have normalized.
9.) Iron overload @ beginning of tx but now low.
10.) F1 @ start of tx with no bridging.

I'm resolved to rid myself of HCV and will continue tx.  

The plan from my doc is the same drugs and doesages but with monthly PCRs looking for a continued drop, undetectable (or worse case stabilized/elevated).  With undetectable my doc will be very aggressive and go 36 weeks or longer.  

IS THIS THE RIGHT COURSE OF ACTION?  Does anyone have data about introducing another drug or interferon that will help shock this thing into undetectable?  Or perhaps more than once per week injections of PEG-Intron?

Once again, thanks for your input and I'll return the favor in the future.  Happy Thanksgiving!  Mike.

[cuteus]

http://www.hcvadvocate.org/
this is a great site that publishes abstracts and articles.

http://www.projectsinknowledge.com/recent/indexg.html
I love reading stuff at this site.

[cuteus]

I would even go longer than 36 wks, for good measure. A member here, don alfonso, took about 7 months to finallly clear, bob l just told his story, Kathie, at another forum, just went undetect at 11 months. she will extend to almost a yr past that mark.
As Scottt said, the dismal results for slow responders come from studies that allowed for only 48 wks of tx, regardless of when they became negative.
The other great suggestion, to customize your dosages to achieve SVR, is worth considering.
please read the hepatitisdoctor.com site for some info on how some drs are customizing treatment.

[Bob L]

Thanks Chev I have always enjoyed your help and spirit here

Bob L

[Bob L]

Sorry about that hit the button to soon



I just finished 72 wks of tx. I did not clear till later myself and decided on pushing it to 72 wks. I say suck it up and do what you have to do to beat this. We are not Doctors but we read and do our home work here and when we are not able to our friends here help and do it for us.

My experience was one of my Docs told me to stop tx and I said B.S. I had a 1.5 log drop at I think 12 wks and then my viral load kept dropping. and I was in the 4000's and then in the 100's and then I was 30 and then I was clear. I am still clear and I feel I have a good chance of maitaining SVR so it is your choice but read, read, read and make your own choice some Docs are just not up on latest findings. WE need to be it our LIVES!


Good Luck

Hey all my friends here have a great Turkey day. I am feeeeling better since I stopped Interferon and especially the Riba.

GOD BLESS

Bob L     formally Ral (I could not post one day so I just changed my nick name

[Bob L]

Miked

[DoubleDose]

PS

Britgirl is correct, generally therapy would be discontinued as a result of not becoming undetected by week 24...but in your case, there are other variables to consider, AND, the possibility of changing the entire dosing paradigm, by bumping up the dosages, and keeping them at the increased levels...MAY do the trick, and MAY be what you needed from the beginning.  There has not been much research around ADJUSTMENTS to dosing, for people not getting undetected by week 24.  Most of our discouraging data comes from 24 week detecteds, who finished out the 48 weeks using the SAME dosage, AND who did not extend therapy.  In those studies, the SVR rate dropped to about 3%....
BUT, they did not use flexible, creative approaches, that now are being used from the beginning, to increase the SVR results.  You MAY just need a different regimen, AND you are very close to the 24 week undetected level....If you adjust, and get undetected in the next 4-6 weeks, YOU may indeed have a good shot at SVR.  I think it is worth a real attempt.  You have come too far, and I do not believe that scrapping the entire tx is the best strategy.  On the other hand, I think you do need to be aggressive, move quickly, and monitor whether or not it causes a rapid undetected result.  If that happens...you just need to stay on the dosage level that gets you there, for a long, long time.  Going for a full year at undetected (by VERY sensitive PCR testing) could give you high odds of success.  You just need to get undetected, and QUICKLY!!!!  (My Opinion, of course)

DD

[honey1616]

You are responding to medicine which is a good sign.  If it was me,,,I would follow your drs advice and continue and once you reach "undetectable",,,then go another 36 weeks past that.  People that are 1's are clearing so hang in there but just taking some extensions and determination...Good Luck!

[DoubleDose]

My questions would involve the following:
1.  What type of interferon are you using?
2.  What  dosage level?
3.  What is your height, weight, genotype, duration of infection?
4.  How much Ribavirin (or Copegus) are you taking?
5.  Have you treated before this tx?


Possible strategies, depending on the above answers include:

1.  RAISE the interferon dosage, to bump the viral decline curve.  You have obviously hit a resistance level, and need more horsepower.  Note:  This MAY not work, but SHOULD work.
2.  Change to a different interferon...especially if you are on Pegasys.  Going to Peg-Intron may be more powerful, and may be more flexible as far as dosing levels.  You can more easily do MORE than standard protocol with Peg-Intron.  Another choice would be daily, high dose infergen, using 15 mcg. / day.
3.  Make darn sure you are using the very maximum allowable Ribavirin dosage for your weight.
4.  Keep pushing until you do get undetected, using some combination of above strategies, and then go AT LEAST the 36 weeks after first undetected result, as your doc suggests.  I would seriously consider going for 52 weeks minimum, AFTER clearing.

Please take heart:  You are responding, you are just a slow responder, and are probably taking a sub-optimal dosage of drugs necessary to getting the proper decline curve.  You DID get the necessary 2-log drop at 12 weeks, but have bogged down, and need an adjustment , in order to really give you good odds.  You most definitely will need extended therapy, if you do indeed become undetected.  Please let us know all your variables, regarding the above questions, so that you might receive appropriate suggestions from the members of the forum.  Many of us have been there in the past, and had to get creative in order to get our SVR's.  I had to do a 'double dose' of Peg-Intron, in order to get the right decline curve, and still needed to extend to 18 months.  This is just my opinion, please consult your doc, and/or top prominent HCV practitioners, with lots of exp. treating difficult responders!  This period of tx is very critical to your success.

Good Luck!!!!  Don't give up, just push harder!  You are in a position to overcome this obstacle, and win.

Doubledose

[britgirl]

In the UK you would be taken off the medication if you had not cleared the virus by 24 weeks. I am willing to believe that is because we only do 48 weeks max, there is no culture of extended tx (as far as I know). I don't wish to be too pessimistic, but I do think your chances of clearing the virus are slim. However, "slim" may be enough for you to feel happy about continuing.

[miked]

Thanks.  I've seen your logon at hepCnet; you are knowledgeable on the topic.  How do you know that I'll go undetectable and not stay at 5,000 or elevate?  My inclination is to suck it up and stay the course.  Mike.