Add -on interferon to a stable nucleoside, hbsag loss 40% full poster

[stef2011]

https://docs.google.com/open?id=0B_yFgxI8KNcROTI2YzFkYTctMjZjMy00MjBjLWE0ZDEtNWY3NmI0MDQ3MzNl

this is very important because we can make the following comments:

adefovir had the higest results but since tenofovir is similar with less toxicity, more potency and no resistance we maight have same or higher results

another observation is etv mono for only 3 years and huge hbsag decrease from 7900iu/ml.while all others had already very low levels of hbsag this patient had response on the hbsag range where interferon mono has little decrease on hbsag.the decrease looks also a sudden decrease and not slow and homogeneous

too bad we dont have etv+tdf combo among these patients i guess it may have stronger effect

[mer971]

Steff, I just want to thanks for all this info, you are such a helpful guy on this forum. Dio ti benedica

[stef2011]

to note peg was kept for 96weeks and then stopped keeping nucs only

i think this is a mistake if there is a trend of hbsag decline like on those patients at 100-130iu/ml, if there are no significant sides it is best to keep pegintf until hbsag und or at 10-20iu/ml where hbsag clearance in the follow up is more certain

i remember a chinese trial keeping pegintf, but monotherapy, for those with hbsag decline and the hbsag rate was very very high

[stef2011]

here is the link at page 23 with the chart

http://www.aphc.info/pdf/2014/Luncheons_13012014/S-242A/Denis_OUZAN.pdf

[stef2011]

i have found the update to this trial at week 120 and hbsag loss went from 4 patients to 6 patients, the 3 remaining responders hbsag from 100 to 130iu/ml which is sure clearance in the follow up
the non responder who stopped peg at 24 weeks had a decline of hbsag too from 1754 to 1000iu/ml (i would have not stopped peg at 24weeks)

https://docs.google.com/open?id=0B_yFgxI8KNcROTI2YzFkYTctMjZjMy00MjBjLWE0ZDEtNWY3NmI0MDQ3MzNl

[4est]

good luck!

and keep us updated  ;)

[stef2011]

i think that will be my trial

[4est]

and another clinical trial that have to keep an eye on it:

http://clinicaltrials.gov/ct2/show/NCT00877760?cond=Hepatitis+B&cntry1=EU%3ARO&rank=3

[4est]

A new trial for tnf + inf  is in recruitment phase:

http://clinicaltrials.gov/ct2/show/study/NCT01277601?term=hepatitis+b&recr=Open&cntry1=EU%3ARO&rank=1&show_locs=Y#locn

this is a trial that we have to look for the results.

[stef2011]

http://www.kenes.com/easl2010/orals/118.htm
this was peg+telbivudine (ltd) 24-48weeks with hbsag 0.5log decline on 63%

Background and aims: HBeAg seroconversion is a key milestone for HBeAg-positive chronic hepatitis B (CHB) patients allowing for treatment discontinuation. Compared with other treatments, higher rates of HBeAg seroconversion (e-seroconversion) are reported with PegIFN or LDT. We aimed to investigate whether PegIFN+LDT combination could further improve antiviral efficacy and e-seroconversion compared to their monotherapy.
Methods: 159 HBeAg-positive CHB patients were randomized (55 LDT, 54 PegIFN, 50 PegIFN+LDT). 110 patients (49 LDT, 43 PegIFN, 18 PegIFN+LDT) reached treatment week 24 (W24), but the study was terminated early due to PN events with PegIFN+LDT. Key efficacy (HBV DNA, ALT, HBsAg/HBeAg quantitation by Abbott Architect) and safety is reported.
Results: Mean baseline HBV DNA levels (log10copies/mL) were 9.8 (LDT), 9.6 (PegIFN), 10.1 (PegIFN+LDT). At W24, LDT containing regimens achieved significantly greater viral load decline than PegIFN (figure 1).
HBV DNA became undetectable in 35%, 7% and 71% of patients (LDT, PegIFN and PegIFN+LDT, respectively), p0.5log10IU/mL) occurred in 41% LDT, 31% PegIFN and 63% PegIFN+LDT treated patients (p=0.03); ALT normalization: 54% LDT, 32% PegIFN, 12% PegIFN+LDT. For the few LDT and PegIFN patients who achieved W48, 7/19 and 3/12 respectively had e-seroconversion.
ITT discontinuations due to SAE/AE occurred in 7.3%, (LDT), 5.6% (PegIFN) and 18%, (PegIFN+LDT). PN cases with PegIFN+LDT were more severe and shorter median time (months) to symptom (4.5, range 2-6) vs LDT (14, range 4-25). 9 SAE PN cases were drug related, 8 were on PegIFN+LDT, 1 was on LDT and at last follow up, 6 were improving, 2 ongoing and 1 unknown.
Conclusions: The combination of PegIFN+LDT provided very potent antiviral efficacy with rapid and profound reduction in HBV DNA and HBsAg/HBeAg levels, but combination therapy with PegIFN+LDT carried an increased risk of PN. The underlying mechanism needs further investigation. Despite increased efficacy, concomitant use of PegIFN+LDT should be avoided at present.

[4est]

http://www.medhelp.org/posts/Hepatitis-B/wow-found-post-of-a-guy-who-cleared-after-48weeks-combo-interferontelbivudine-in-italy/show/1643426

just to keep all information in the same place :)

[stef2011]

thank you very much for finding the emails but i have just returned from pisa and they know already that hbv is cleared by combo int+tdf or int+etv, just a matter of time to clear almost all of hbsag.

so now we just need to make these combos and see how hbsag goes down and personalize interferon+nucs durability according to it:

for example interferon+tdf or etv doesn t lower hbsag by 24 weeks, stop interferon and continue the antiviral only.interferon can be retried later on

if hbsag keeps lowering the combo must be kept as long as hbsag detactable, even 2-3 or more years

[4est]

http://www.medhelp.org/posts/Hepatitis-B/news-from-researchers-interferontdf-or-etv-clears-hbv-in-almost-all-patients-96weeks/show/1643024

to have tractability for all related topics

[4est]

"can we use INTALFA (Recombinant Interferon Alfa-2b) available in india?" - treatment have to be done under the doctor surveillance and authority, so beter look for a good doctor.

as for INTALFA, better check with the doctors from India (they know the market) and also with the drug producer (for me it sound like a interferon and not peg interferon (and in this case the dosage is different ))

[4est]

yes, tenofovir has the same dosage for HBV and for HIV

[raja1972]

can we use INTALFA (Recombinant Interferon Alfa-2b) available in india?

reference site is:
http://www.intasbiopharma.co.in/Interferon.html

[raja1972]

what is the tenofovir and entecavir  dosage  (is the tenofovir the same used for HIV patients?)

[raja1972]

Hi steff,
Pls refer to the link for the email addresses.

http://www.springerlink.com/content/bl027j04p7488704/fulltext.pdf

[raja1972]

denis ouzan -  denis.***@****

Guillaume Pénaranda -- g.***@****
Guillaume Pénaranda - g.penaranda@ alphabio.fr


Marc Bourličre - [email protected];


Hacène Khiri -  h.khiri@alphabio. fr

Philippe Halfon - philippe.***@****

[stef2011]

that's a very good study made by a university.the most important thing is to find studies not funded by drug makers because they dont supply data, on the contrary they made combo study from a long time and never published data

i used to go to interferon drug maker website because they used to say data will be published by.......they never did and we know why now

[4est]

http://clinicaltrials.gov/ct2/show/NCT00973219?term=hepatitis+b&recr=Open&cntry1=EU%3ANL&rank=3 - this is another study that we have to keep an eye on him and also to try to contact the researchers.
this is one of few study that have INF+TNF and also claim a result that I was not able to found in previous study " ... Recently the investigators have shown that HBeAg negative patients with high HBV-DNA load and low baseline HBsAg levels had a significantly higher HBsAg clearance (positive predictive value of 85%) after combination therapy with peginterferon alfa2a (Peg-IFN) and adefovir" - notice that this affirmation is from 2009.

[4est]

"i was looking how to contact the doctors of this poster because 40% clearance is by 48weeks already while the other patients are still on therapy until 96weeks.the other patients have hbsag between 30-300iu/ml by 72 weeks and till decreasing" - for sure I will follow-up this presentation. I hope that they will came with an update on the flowing sessions, but until then I will try to find as many information as possible by contacting the doctors.

[stef2011]

i dont know if word can display ppt or openoffice files, open office is the best to display all formats

[stef2011]

the file is native ppt file, i ve uploaded as openoffice file to be displayed correctly.i dont know if work can display ppt or openoffice files

https://docs.google.com/open?id=0B_yFgxI8KNcRMDExNmMzYzUtOWE1Ny00NWY5LWE5OTctZGU0YzBhYWNhYjk0

[stef2011]

i ve uploaded native pdf, download here because with google docs conversion there is loss of data and it is less clear

low viremia under nucs
https://docs.google.com/open?id=0B_yFgxI8KNcRMWU5MmY5MTgtNzNiOC00YWQ1LWFjZGEtNjA0MTU4ZWJiN2Rj

my guess is maximum suppression plus active immune system will clear much of cccdna faster