Clinical relevance of detectable but not quantifiable hepatitis C virus RNA during boceprevir or telaprevir treatment.

[can-do-man]

Clinical relevance of detectable but not quantifiable hepatitis C virus RNA during boceprevir or telaprevir treatment.
Harrington PR, Zeng W, Naeger LK.
Source
Division of Antiviral Products, Office of Antimicrobial Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993. Patrick.***@****.
Abstract
Boceprevir- and telaprevir-based treatments for chronic hepatitis C virus (HCV) infection use specific response-guided therapy (RGT) guidelines. Eligibility for shortened treatment duration is based on achieving Undetectable HCV RNA early during treatment. It is unclear whether a detected HCV RNA level that is below the assay lower limit of quantitation (Detectable/BLOQ) is comparable to an Undetectable HCV RNA level, particularly regarding RGT decision making. We analyzed data from boceprevir and telaprevir clinical trials to obtain a comprehensive understanding of the frequency and clinical relevance of Detectable/BLOQ HCV RNA measurements. In Phase 3 trials P05216 (boceprevir), C216 (telaprevir) and 108 (telaprevir), Detectable/BLOQ levels were reported for approximately 10-20% of all on-treatment HCV RNA measurements. In P05216 and C216, subjects with Detectable/BLOQ HCV RNA, on average, had a reduced sustained virologic response (SVR) rate compared to subjects with Undetectable HCV RNA at the same on-treatment timepoint. At key RGT timepoints (Week 8 for boceprevir, Week 4 for telaprevir), subjects with Detectable/BLOQ HCV RNA had an approximately 20% lower SVR rate compared to subjects with Undetectable HCV RNA, and this difference widened for later on-treatment timepoints. A similar trend was observed for Study 108, but the differences in SVR rates were more modest, which may be explained by a higher frequency of reported Detectable/BLOQ results. Analyses of Phase 2 boceprevir and telaprevir trials indicated subjects with Detectable/BLOQ HCV RNA at RGT timepoints benefited from extended treatment duration.

CONCLUSIONS: During boceprevir- and telaprevir-based treatment, subjects with Detectable/BLOQ HCV RNA had a reduced virologic response compared to subjects with Undetectable HCV RNA. Eligibility for shortened treatment duration should be based on patients achieving Undetectable HCV RNA at RGT decision timepoints. (HEPATOLOGY 2011.).
Copyright © 2011 American Association for the Study of Liver Diseases.

http://www.ncbi.nlm.nih.gov/pubmed/22095516

[eureka254]

can-do-man:  Excellent info for those currently on triple on the pivot of 12 week results and length of treatment.  

willbb:  Think you hit the nail on the head.  Just as in early years of treatment relapse rates were high using VL und based on <615, we've hit a point in understanding of hcv where higher sensitivities and finer distinctions need to be made to optimize treatment response. Mayo's experience really underlines the need of both patients and medical professionals need to utilize better strategies when 'standard' tests don't address individual needs.  Using the <5 or <2 as the 4wk and 12wk markers would so better serve everyone as a whole, imho.  

[Aquisi]

Thanks Will, I understand now, everything seems so confusing at first. This is all a learning process, as I keep reading everything falls into place, until tomorrow when I'll forget.lol (I need a lot of repetition).

[willbb]

So according to the Mayo Clinic, <43 does not mean UND as the posting from Can-do states because under 43 can not be quantified? I may be missing something here.
--------------------------------------------------------------------------------------------------------------
No your are not missing anything. The test you mention can be DET. or UND.  
Often on this result (<43) there is still virus DET. ,however thy can not quantify it(still low level virus,and this is considered for extending therapy)

However it may be <43 UND. where it is below the qunatifiable number and also  there is no virus  detected.

I agree with  Dave &cando ..the more sensitive tests  <25 (mentioned above),  <5(Quest Heptimax) or the <2 (Labcorp Quantisure) should be used,given there is a lot at stake  and many doctors don"t seem to be as familiar with the reports  as  should be.

Will

[hrsepwrguy]

I live in a fairly small community and the docs around here really have no exp using the new PI's and are not required to do continued education on the meds unless they choose to, big problem, thank goodness I only live an hour away from a metroplex and travel to a teaching hospital for treatment though a trial, I do see a local GI for more frequent CBC's and RX's for side effects but all tx decisions have to be approved through tx team at UC Denver as to their tx protocol. As far as PCR results all mine have either said DET under limit of quan or UND below LOD.

[can-do-man]

"It's not very complicated if treating Drs use the same PCRs that are at least as sensitive as those used in the trials for Vic and Inci. I don't know why some are not since they are available. Personally I would question my doc who is supposedly knowledgeable  about the PIs not using the proper tools to oversee tx."

Dave, i am at a lost on how alot of these doctors are even treating some people, let alone doing a pcr.

[spectda]

It's not very complicated if treating Drs use the same PCRs that are at least as sensitive as those used in the trials for Vic and Inci. I don't know why some are not since they are available. Personally I would question my doc who is supposedly knowledgeable  about the PIs not using the proper tools to oversee tx.

This is the labcorp test used in the Victrelis trials. If someone wants a test that is even more sensitive they can use the labcorp quantasure or the quest heptimax but they will have to wait longer for a result.

Hepatitis C Virus (HCV), Quantitative, Real-time PCR (Graphical)
HCV RNA Quantitation, TaqMan®
Test Number: 550070

"The limit of detection of this assay is 7.1 IU/mL for HCV genotype 1, and the quantifiable range of the assay is 25 IU/mL to 69,000,000 IU/mL."

[Aquisi]

For the purposes of assessing response-guided therapy eligibility, an "Undetected" result is required; a "Detected" result below the limit of quantification should not be considered equivalent to an "Undetected" result.


So according to the Mayo Clinic, <43 does not mean UND as the posting from Can-do states because under 43 can not be quantified? I may be missing something here.

[willbb]

Hi Dee.. the 1.63 is nothing to worry about . It is just another way of saying <43  but in log form.
If the report says <43UND. then you are UND. I agree with cando.ask for hard copies of your PCR report,..if they refuse ..be persistant .
Best ..
Will

[can-do-man]

Ask for a copy, that should not be a problem............. From what you wrote you are UND.

[Dee1956]

Mine says <43 UND
Then there is another # <1.63
The Doc and PA say I am UND I am worried since they do not want to give me in writing, just show me on their laptops what should I ask for?

Thank you
Dee

[frijole]

Wow - can do where did you find this.  This is the information I like to see.  And that Mayo clinic info makes it quite clear, doesn't it? Undetectible does not mean detectible but under 43.  I think we will see a lot more of this type of data in the next year ---  but how can they even put together the stats unless Quest starts to qualify their <43 test.

Will -- You know Kwo was can-do's treatment doctor, don't you?  I have more respect for him that about anyone I can think of.  Thank you for the link.

frjiole

[rockymoe]

Thank you. I learn so much from you!

[hrsepwrguy]

Thanks will that looks much more promising than the 60% I was seeing, and I am tolerating tx well only bloodwork problem so far is low lyphocytes which are at a .4 but monitoring hepa has no concerns and am still on full inf dosage.

Keith

[flcyclist]

Thanks for sharing candyman.  It makes understanding the PCR results even more important now.  

[willbb]

Keith..Don"t know if you are registered with CCO or not . If so, go to this site and  then go to the " Slides"   not the " launch program "   and there is some info. there you may find helpful. Scroll to the slide titled :

"SVR Rate BY HCV RNA Status (LLOQ vs. LLOD) for  Boce & Tela "

.http://www.clinicaloptions.com/Hepatitis/Treatment%20Updates/HCV%20Assays.aspx

Hope all is well..
Will

[hrsepwrguy]

I think I found it in the tela advance 108 study, it is a little unclear to me, it shows a 60% SVR rate with no eRVR and 48 wks of tx but only a 4% relapse rate over all and a 7% break though rate during tx.

[hrsepwrguy]

Do you have any SVR stats on people like me that were under 43 at wk 4 but UND at wk 12 if they do the full 48 wks which is what my treatment plan is, not that it really matters because I plan to follow the treatment plan as long as I am UND at 24 wks but would like to see what the true stats are.

[can-do-man]

Morning Deb, also this from the mayo clinic.

A "Detected" result with the comment "HCV RNA level is <43 IU/mL (<1.63 log IU/mL). This assay cannot accurately quantify HCV RNA below this level." indicates that the HCV RNA level is below the lower limit of quantification for this assay. When clinically indicated, follow-up testing by this assay is recommended in 1 to 2 months. For the purposes of assessing response-guided therapy eligibility, an "Undetected" result is required; a "Detected" result below the limit of quantification should not be considered equivalent to an "Undetected" result.

[nygirl7]

Very very interesting Dr. B.  Makes all the folks who want to quit early look like they should reconsider UND is UND anything else is not. But we knew that, just not that the odds potentially went down from 80% to 60%. That's huge.