24-week deadline for 72-week extenders?

[smaug48]

My week 20 and 22 pcr's were 194 and 99, respectively.  My NP said that the 24-week deadline for undetectable is seeming more and more not to apply to people who extend to 72-weeks.  She said the hospital where I am going has continued to treat patients who didn't get to undetected until week 30.  She didn't tell me if anyone in that situation SVRed or not.

Any SVR's out there (geno 1) that didn't get to undetected until after week 24 and treated 72 weeks?

smaug

[smaug48]

Thanks for your post.  I got a 2-log drop by week 12, so have already decided to extend to 72 weeks.  My understanding is that the 24-week deadline for undetectable is largely based on studies using 48-week treatment only.  There isn't much data on going 72 weeks, and some doctors, including my own, believe that a 24 week deadline for undetectable isn't appropriate for someone who is planning on treating 72 weeks.

Hence I was hoping to find out if there was anyone out there who went undetectable after week 24, treated 72 weeks, and SVRed.

Thanks for the wishes of good luck, I can use them!

smaug

[HectorSF]

I'm sorry to hear that your viral load hasn't become undetectable at this point in your treatment. You must at least be on week 23. Maybe by week 24? Persons who go from a more than 2 log drop to undetectable between weeks 12 and 24 should be treated for 72 weeks in order to have the best chance of SVR.

Below is a recent paper by one of the leading researchers in the study of Hepatitis C. According to his studies if you don't because undetecable by week 24 you have no chance of SVR. Treatment needs to be modified in order to drop your VL to undetecable, otherwise treatment should to stopped.

"Understanding HCV Nonresponse and Identifying Candidates for Retreatment"
Source: New Management Strategies for HCV Nonresponders and Relapsers
By: Mitchell L. Shiffman, MD
Chief Hepatology Section
Medical Director, Liver Transplant Program
Virginia Commonwealth University Medical Center
Richmond, VA

http://clinicaloptions.com/Hepatitis/Treatment Updates/HCV Nonresponders/Module/Shiffman.aspx

Defining the Patterns of Virologic Response and Nonresponse
Virologic response patterns can be divided into 3 groups (Table 1): 1) those that lead to virologic response where the patient achieves undetectable HCV RNA, 2) those associated with nonresponse where the patient does not achieve undetectable HCV RNA, and 3) those associated with an initial virologic response which is subsequently lost either during treatment (breakthrough) or after treatment has been discontinued (relapse). It is important to realize that only those patients with a virologic response in which HCV RNA becomes and remains undetectable throughout treatment can achieve an SVR. Continuing treatment in patients with a virologic pattern of nonresponse or breakthrough will not lead to SVR. As a result, it is imperative that the patterns of virologic response and nonresponse be recognized. These patterns can only be accomplished by assessing HCV RNA at monthly intervals until the HCV RNA has become undetectable or a nonresponse pattern has been defined.

Approximately 15% of genotype 1 patients have a ≥ 2 log10 IU/mL reduction in HCV RNA and therefore have an EVR but never achieve undetectable HCV RNA.[7] These patients are referred to as having a partial virologic response. Since these patients do not achieve undetectable HCV RNA by Week 24, there is no possibility of SVR being achieved if the same therapy is continued. Treatment must either be discontinued or modified as soon as partial virologic response has been recognized. Partial virologic response can only be identified if HCV RNA is monitored on a regular basis through Week 24.

Partial Virologic Response
Patients with partial virologic response are excellent candidates for retreatment. These patients elicited an initial response to interferon-based therapy and exhibited a 2 log10 IU/mL or greater decline in HCV RNA during the first 12 weeks of treatment. If these patients are treated with higher doses of interferon or peginterferon alfa, they can potentially achieve a greater decline in HCV RNA, perhaps achieving undetectable values and, in some cases, SVR (Capsule Summary).[32] Unfortunately, most retreatment studies have not characterized the previous virologic response pattern, and the relative percentage of null and partial responders is commonly unknown. However, in 2 studies, the previous response pattern was well characterized. In the first study, a population of patients with previous nonresponse to standard interferon were retreated with a higher dose of standard interferon and ribavirin. Only 13% of patients achieved an SVR. However, all of these responders had also achieved a partial response during their initial course of therapy; no previous null responders achieved SVR.[33] In the second study, patients with a previous nonresponse to standard interferon and ribavirin were retreated with peginterferon alfa and ribavirin.[34] Overall, 28% of patients in this study achieved an SVR. However, 75% of these patients had a partial virologic response during the initial course of treatment. In an interim report of another study, the REPEAT trial, patients with nonresponse to peginterferon alfa-2b and ribavirin were retreated with either standard-dose (180 µg/week) or high-dose (360 µg/week) peginterferon alfa-2a (Capsule Summary).[35] After 12 weeks of treatment, the percentage of patients who achieved undetectable HCV RNA was 17% greater with the higher dose of peginterferon alfa-2a compared with the standard dose. Final SVR results will be required to see if the advantage of high-dose peginterferon alfa treatment remains. Based on these observations, it has been hypothesized that some patients with a partial treatment response can achieve undetectable HCV RNA if switched to a more intensive interferon regimen. The time at which to intensify the interferon regimen can be anywhere between 12 and 24 weeks. However, the patient must be able to tolerate the higher dose of peginterferon alfa and be motivated to continue with treatment. The major limitation to this strategy is firstly the accessibility of higher dose of peginterferon alfa to many patients, as it is unlikely to be approved by many insurance companies without more concrete data supporting this approach and, secondly, the increase in the discontinuation rates because of tolerability issues. In patients treated with a more intensive interferon regimen, HCV RNA should continue to be monitored at monthly intervals. If the patient does not achieve undetectable HCV RNA within 12 weeks of dose intensification, treatment should be discontinued. By contrast, if the patient does achieve undetectable HCV RNA, this treatment should be continued for an additional 48 weeks. This is the typical duration of extended treatment in patients with slow virologic response.

Identifying Candidates for Retreatment: Insufficient Treatment Duration
Patients with a slow virologic response have a high rate of relapse. This is true both for patients with HCV genotype 1 who achieve undetectable HCV RNA more than 12 weeks after the onset of treatment[7] and patients with genotypes 2 or 3 who achieve undetectable HCV RNA after Week 4.[3] Genotype 1 patients with a slow virologic response during their initial course of therapy are excellent candidates for retreatment for a longer duration of 72 weeks. For patients with genotypes 2 or 3 who relapsed after their initial course of treatment, retreatment for a longer duration, from 24-48 weeks, is also a logical approach and supported by a retrospective analysis.[21] However, no prospective data are available to support this approach.

Best of luck to you!
Hector