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<a href="http://www.hivandhepatitis.com/hep_c/news/2005/ad/060605_c.html">Peginterferon Alfa-2b (PegIntron) and Ribavirin for Chronic HCV Patients Who Relapsed or Were Non-responsive to Interferon/Ribavirin</a>
(from the study):
"<i>The authors conclude,
(from the study):
"<i>The authors conclude,
I suspect a lot of that hesitation and debate goes back to the principle of "first do no harm" (regardless of whether that phrase is not in the Hippocratic oath). Though the Ferenci paper definitely reinforces the 12-week rule and the overall importance of early viral drop it only <i>speculates</i> about the possible benefits of longer duration or higher dosage:
"The high relapse rates in patients with a delayed virological response <i>may</i> indicate that treatment was not administered for a sufficient duration. Thus further improvement in SVR rates in patients with genotype 1 <i>might</i> be achieved by increasing the initial dose of peginterferon alfa-2a (40 KD) and/or by prolonging the duration of therapy. Higher SVR rates in response to more rapid viral clearance have been obtained with high doses of conventional interferon alfa in prospective randomized controlled trials [13] and [14]. Prolongation of treatment in slow virological responders (ie in patients with an EVR at week 12 but who remain HCV RNA positive) <i>may</i> decrease relapse rates in end of treatment responders. The feasibility of this approach <i>is being tested</i> in prospective trials. "
Their references <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11679972&query_hl=3">14</a> and <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11172344&query_hl=5">13</a> are definitely not new data. In short, while higher ifn dosage and/or longer duration may very well be shown to help 1s, this remains to be proven (and there is fair amount of data showing that higher dosages/longer durations does not always help - eg high riba or longer duration for 2s).
"The high relapse rates in patients with a delayed virological response <i>may</i> indicate that treatment was not administered for a sufficient duration. Thus further improvement in SVR rates in patients with genotype 1 <i>might</i> be achieved by increasing the initial dose of peginterferon alfa-2a (40 KD) and/or by prolonging the duration of therapy. Higher SVR rates in response to more rapid viral clearance have been obtained with high doses of conventional interferon alfa in prospective randomized controlled trials [13] and [14]. Prolongation of treatment in slow virological responders (ie in patients with an EVR at week 12 but who remain HCV RNA positive) <i>may</i> decrease relapse rates in end of treatment responders. The feasibility of this approach <i>is being tested</i> in prospective trials. "
Their references <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11679972&query_hl=3">14</a> and <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11172344&query_hl=5">13</a> are definitely not new data. In short, while higher ifn dosage and/or longer duration may very well be shown to help 1s, this remains to be proven (and there is fair amount of data showing that higher dosages/longer durations does not always help - eg high riba or longer duration for 2s).
This is the NATAP paper of the above "Predicting SVR ..." article:
<a href="http://www.natap.org/2005/HCV/060605_01.htm">Predicting SVR: 12 Better than 4 Week Early Viral Response</a>
(from the paper):
"<i>...the results of this analysis provide further support for assessing virological response after 12 weeks of treatment with peginterferon alfa-2a (40KD)/ribavirin, rather than at week 4....although 87% of patients with undetectable HCV viral load at week 4 achieved an SVR, the ability to predict who will NOT achieve an SVR is better after 12 weeks of therapy.... Perhaps the most intriguing new finding of this analysis was the consistent evidence of a relationship between the rapidity of HCV RNA suppression and the likelihood of achieving an SVR... the importance of adherence to therapy was reconfirmed...high relapse rates may indicate SVR might be improved by increasing initial dose of Pegasys and/or prolonging the duration of therapy...</i>"
"<i>Perhaps the most intriguing new finding of this analysis was the consistent evidence of a relationship between the rapidity of HCV RNA suppression and the likelihood of achieving an SVR. Furthermore, the high NPV of the absence of an EVR at week 12 and the importance of adherence to therapy was reconfirmed and serves to reinforce the recommendations in the NIH Consensus Statement [4]. These data can be used to tailor treatment for individual patients.</i>"
<a href="http://www.natap.org/2005/HCV/060605_01.htm">Predicting SVR: 12 Better than 4 Week Early Viral Response</a>
(from the paper):
"<i>...the results of this analysis provide further support for assessing virological response after 12 weeks of treatment with peginterferon alfa-2a (40KD)/ribavirin, rather than at week 4....although 87% of patients with undetectable HCV viral load at week 4 achieved an SVR, the ability to predict who will NOT achieve an SVR is better after 12 weeks of therapy.... Perhaps the most intriguing new finding of this analysis was the consistent evidence of a relationship between the rapidity of HCV RNA suppression and the likelihood of achieving an SVR... the importance of adherence to therapy was reconfirmed...high relapse rates may indicate SVR might be improved by increasing initial dose of Pegasys and/or prolonging the duration of therapy...</i>"
"<i>Perhaps the most intriguing new finding of this analysis was the consistent evidence of a relationship between the rapidity of HCV RNA suppression and the likelihood of achieving an SVR. Furthermore, the high NPV of the absence of an EVR at week 12 and the importance of adherence to therapy was reconfirmed and serves to reinforce the recommendations in the NIH Consensus Statement [4]. These data can be used to tailor treatment for individual patients.</i>"
This is the NATAP paper of the above "Predicting SVR ..." article:
<a href="http://www.natap.org/2005/HCV/060605_01.htm>"Predicting SVR: 12 Better than 4 Week Early Viral Response</a>
(from the paper):
"<i>...the results of this analysis provide further support for assessing virological response after 12 weeks of treatment with peginterferon alfa-2a (40KD)/ribavirin, rather than at week 4....although 87% of patients with undetectable HCV viral load at week 4 achieved an SVR, the ability to predict who will NOT achieve an SVR is better after 12 weeks of therapy.... Perhaps the most intriguing new finding of this analysis was the consistent evidence of a relationship between the rapidity of HCV RNA suppression and the likelihood of achieving an SVR... the importance of adherence to therapy was reconfirmed...high relapse rates may indicate SVR might be improved by increasing initial dose of Pegasys and/or prolonging the duration of therapy...</i>"
"<i>Perhaps the most intriguing new finding of this analysis was the consistent evidence of a relationship between the rapidity of HCV RNA suppression and the likelihood of achieving an SVR. Furthermore, the high NPV of the absence of an EVR at week 12 and the importance of adherence to therapy was reconfirmed and serves to reinforce the recommendations in the NIH Consensus Statement [4]. These data can be used to tailor treatment for individual patients.</i>"
<a href="http://www.natap.org/2005/HCV/060605_01.htm>"Predicting SVR: 12 Better than 4 Week Early Viral Response</a>
(from the paper):
"<i>...the results of this analysis provide further support for assessing virological response after 12 weeks of treatment with peginterferon alfa-2a (40KD)/ribavirin, rather than at week 4....although 87% of patients with undetectable HCV viral load at week 4 achieved an SVR, the ability to predict who will NOT achieve an SVR is better after 12 weeks of therapy.... Perhaps the most intriguing new finding of this analysis was the consistent evidence of a relationship between the rapidity of HCV RNA suppression and the likelihood of achieving an SVR... the importance of adherence to therapy was reconfirmed...high relapse rates may indicate SVR might be improved by increasing initial dose of Pegasys and/or prolonging the duration of therapy...</i>"
"<i>Perhaps the most intriguing new finding of this analysis was the consistent evidence of a relationship between the rapidity of HCV RNA suppression and the likelihood of achieving an SVR. Furthermore, the high NPV of the absence of an EVR at week 12 and the importance of adherence to therapy was reconfirmed and serves to reinforce the recommendations in the NIH Consensus Statement [4]. These data can be used to tailor treatment for individual patients.</i>"
The above study reinforces what I have come to believe, and expounded upon recently in a post regarding slow response. If you are going to attempt to go for SVR, you had better get the 2-log by week 12, and if you need to speed up the response, adding more interferon is one very good way to often achieve that goal. For those who are still detected at 12 weeks, but who get the 2-log drop, then just increase the length of treatment, according to how long it takes to get the undetected after week 12. In those cases of slow response, but still achieving the 2-log, a great way to really help insure success, is to not only extend the tx duration, but to also bump the interferon up a bit.
I am always amazed that there has been so much hesitation and debate within the medical community regarding the above tactics (which are all confirmed by the study cited). It also makes tons of logical sense. I always feel bad for the patients who have been so limited by some doctors that only think 'inside the box', and the doctors that need a lightening bolt in order to try something a little bit creative to achieve the response targets.
Hopefully studies like the above will open the doors to more customized therapies, and provoke less pessimism among the medical practitioners who only see 'responders' or 'non-responders'!
Thanks again for the high quality information, as always. You do a great service to the new patient, and to those who may not have the necessary data to debate with their doctors, in order to obtain the most current treatment approaches.
DoubleDose
I am always amazed that there has been so much hesitation and debate within the medical community regarding the above tactics (which are all confirmed by the study cited). It also makes tons of logical sense. I always feel bad for the patients who have been so limited by some doctors that only think 'inside the box', and the doctors that need a lightening bolt in order to try something a little bit creative to achieve the response targets.
Hopefully studies like the above will open the doors to more customized therapies, and provoke less pessimism among the medical practitioners who only see 'responders' or 'non-responders'!
Thanks again for the high quality information, as always. You do a great service to the new patient, and to those who may not have the necessary data to debate with their doctors, in order to obtain the most current treatment approaches.
DoubleDose
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