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Non-invasive biomarkers of response to intervention
Jerôme Boursier, University Hospital Center Angers, Angers, France
Thursday, Feb. 20, 2020 · 7 p.m. · 46m 42s
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so much for i've uh inviting me to speak about is very important um
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concept because uh is it follow very nicely the the the talk
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of uh is the better it is important to evaluate a response to
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to to treatment to because in the context of upcoming to drugs for counterpart
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is just something that we have to we have to do some kind of batteries
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so important but also very interesting because there is not so
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much data finally so a lot of discussion to to to have
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so when i prepared the uh the the talk
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i thought how can i organise myself because finally
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it can just as a lot of question there are many and evolution that we can monitor
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or in the context of a treatment for not fall we can what your status this evolution
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we can one thought that this is activity that is arguably the
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don't ask all the construction from the us all the weapons that's cool
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you have also to mourn it or the the two main endpoints that i recommended
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by the f. d. a. and you may that other nash resolution in fibres this improvement
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money to all the evolution of decision we have no several levels of course
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you have clinical parameters we'll discuss about the about these nominees some very simple seems that
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you can you can can get back this is a bit uh already is spoken about that
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we have some biological marker so single well mark a combination of by our marketing but that's
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you have all the yeah so roughly technologies to try something that's worth the pointers
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as to where v. p. dimensional magnetic resonance as a referee and also the emerging technologies
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so to discuss about the uh monitoring these all these tools finally i have
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not so much the done because i can't use the phase two in trials
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the face to a child's use the nonnative test as surrogate
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endpoints so this is not the the the the proposal talk
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we have some phase three trials but very few that have that are ended with positive results
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so many of the of the results we rely on the phase to be trials that are currently available
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so we'll try to to to discuss with you the data that we
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have and also to to trying to find the discussed was the direction
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uh and the possibilities for the for the near future uh in distiller research
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so why is it important
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so today for the tanker trials we need to perform liver biopsy
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at the beginning because we need to this exam to select the patient
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and we need to perform liver biopsy because uh we are
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not able to uh anonymously really evaluate the treatment response to it
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but has is a bit uh say that they are with the
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dries very few responder with the uh uh the rest right study you
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have twenty five percent of their responded that means that you have
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seventy five percent of the past some of the patients well not firsthand
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so in this case what can we do we can change our strategy had and the director also which wasn't right
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and then we need to go back again to leave a biopsy at the end of treatment to see if there is a response
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so once again one quarter of responders another three quarter of lovers on those and
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say that we we have to perform several liver biopsy so encouraging already parts to see
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we have the rubber than others if that's because we don't want to perform a biopsy
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and today in the field of anaphora would definitely for biopsy if we have the patience
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so that's not possible we need none of us if testimony
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top the disease evolution and evolution of evolution the treatment response
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so what does mean treatment plus points so you know that interface we actually we via a
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fist retrial as already uh shown is a bit that's you perform liver biopsy at the beginning
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you perform and there's a liver biopsy uh after a short period so twelve
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to eighteen months to evaluate what most response and today it's done sayings to histology
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so while uh the um it's o. j. and remember the the
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two endpoints that's really important to know a recommended back that you may
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and the f. d. a. out the resolution of nash without was
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something of a fibres is that means that after twelve to eighteen months
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no patience needs to have nobel winning unbelievable you'd
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see absolutely no bloating and all all very little information
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that means that is very restrictive need to actually uh the activity of
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the disease with the single dread that i get so one ought to pathways
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and the second point is the improvement of fibres is at least one stage
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without any worsening of uh of nash but remember that today
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these two endpoints are a a recommended for the conditional approval of drugs
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we don't know factually we don't know if achieving these two endpoints
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associated with a better outcomes of the patients that's wise to concur trials needs a followup area
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up demonstrates that there is a benefit for uh the the outcomes in the in the patients
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and because we don't want to perform liver biopsy we want
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to develop not as fast attack correlated with its too and it's
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so first i was i'd like to emphasise the fact that we have very simple tools
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that we can use to date when it or treatment response the first one is white walls
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so uh as the waiter shows you the results of one study there is a a a result made analyses
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of thirty two studies evaluating the impact
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of white lights on the resolution of evolution
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uh there where more than two thousand and five hundred
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biopsy at the follow up the response was evaluated when yeah
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you are the uh uh i'm mean of twenty five percent reduction of to
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be my one year after the biotech surgery and this net advises show us that
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strong weight loss is associated with a strong response interleave
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uh so sixty c. percent of the patient clear status is
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fifty percent is clearly but i'd variation a swig out of the patient cleared bowling
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and forty percent of the patient at the regulation of uh of of fibres is
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so a simple parameter weight loss had tissue to have an idea of
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what could happen uh in the lever and too many top the treatment response
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and i sure exactly the same study than than than before
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so it was a a clinical trials when when nash patience
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fifty two weeks off exercise and uh
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and i it's a modification so lifetime modifications
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we spell eva biopsy one at the beginning an idea and and you can see that the magnitude of
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an improvement in the activity of the disease any
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nash position was strongly correlated with the weight loss
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and when you would shave ten percent of what your so it's not so much in the patient weight
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eighty kilograms that means h. low weight loss but
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not so much you achieve ninety percent of flash resolution
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so just with white lots with this simple goal you
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are able to have an idea of the the the
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the evolution of the vision of the reader and you are able to money top uh the the the treatment response
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and it was low rents went through all concede the lever
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fibres is improvements so in this study the stratified according to
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the presence of bands line fibres is in the absence of buys line fibres is
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so in those patients with heart fibres is at baseline if you wait
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if you lose more than seventy percent of your uh of of your white
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you can see that there was no progression of liver fibres is the the the white
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and for those patient we didn't achieve at least said percent which was there was some question to progress
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showing that weight loss interested with less that is less activity and as far as just progression
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so let's move to a status is monitoring of sentences so we have many innovative
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test able to to to that how well correlated with a with a status is
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i won't speak about the book test because we know they are they are they are correlated with uh with this
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that is is a a mountain the diva but not so not the not so good correlation you can see that result
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a lot of overlap between the the different upgrades in it exactly the same for all the the status is uh
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a blue test so they're more dedicated for large pretty musical studies that monitoring status is in the single patient
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we have now emerging that thought so the in their i. p. d. f.
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f. you can see that there is a very nice correlation cross sectional study
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between uh the amount of status is evaluated uh using in your
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i. p. d. f. s. and the status is great only for biopsy
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the problem with an i. p. d. f. f. t. e. that it is a a
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not so availability is not a a very uh a chip examination now we have the cat
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and that is an image of the the the at innovation of the transcendental divides in the in the fibres can devices
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you have a a quite nice correlation
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between the the the the cap measurement and
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the status is great so what were we have to learn from the cross sectional studies
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if that cat is able to diagnose that loses but is not so well correlated
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with a with a status is great but yeah it is not the purpose of a
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correlation in a cross sectional studies it's the purpose of monitoring the disease of we should
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and you see doing to talk that cross sectional studies good correlation in cross sectional studies
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doesn't really get remain ability to evaluate into the
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i evaluate the the the evolution of evaluation and treatment
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so once again a a correlation yeah it's uh uh an ancillary study of the
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fin trial that has evaluated give it because you can see the interface to be
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a cross actually you can see that there is a very nice correlation between
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uh and write p. d. f. f. and the status is great and he uh
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you have the evolution of status is those patient who improve with breasts that disease
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uh people biopsy does well stable dollars will send you can
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see that in the right p. d. f. f. was right
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a different between this way categories of patient in those positions
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when programmable see you out the decreasing i. p. d. f. f.
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does west it'll never biopsy there was a source they will ever i. p. d. f. f. and for those was on that was or something
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showing that your i. p. d. f. f. exact rate in questionnaires that you it is
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also an accurately thoughts to money top a step is is a evolution and the syrup
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so we have four status is not as if to able to money top the disease evolution
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so what about cat because every set before the rise act right but the chip does that very available
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so this is the results of a face to a trial so there is no liver
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biopsy it has been present to the leslie per meeting in a in an event but
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uh it's the air a study that i as evaluated in
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the c. c. u. b. to also an artist as it dried
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so you can see here on the left there was a strong degrees instead to this and
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the therapy has evaluated with the right p. d. f. f. and when you use the cat
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there was a degrees but not so not so much or is that a high a completed
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and here you have the different groups of rights with increasing those is there was a does effect
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that was when uh depicted by the any right p. d. f. f. but finally for the cat it was not so
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that's a good kept was not able to to put in like to the
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the the does effect that was seen with the right p. d. f. f.
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this is the only study to mainly that that the that has evaluated kept for monitoring statuses evolution
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uh so this is not very good results but still need confirmation in uh in other studies
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now we have the two right p. d. f. f. that is able to
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money taught to start to this evolution but what does mean a status is degrees
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so if you have a decreases that disease you can
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suggest that suppose that do have degrees new products the city
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so that you have a degrees probably inactivity in many other less progression of i was this this is necklaces
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uh is it very file in the in the study so here it's a small study
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the most at trial that has evaluated is it to be versus placebo in fifty patients
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and what they found they found that the respondents patient so response was define at two
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two point at least two two point decrease the last call so two point agrees inactivity
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in those patients who i shave uh this endpoint to bond degrees in the in the the nasa an escort
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there was a thirty percent degrees instead this is as evaluated within right p. d. f.
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and for those who well known responder yeah right p. d. f. f. was stable suggesting
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that decreases that is is is this your shaded with degrees in activity of the disease
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it has been can feel in another recent study and that's just
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three of the of the fringe trial published by them by this yeah
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uh those patients who where respond uh with the seven point
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at least two point degrees and an escort that was fifty
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percent uh uh the the special where chip thirty percent of the crazy right p. d. f. f.
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half of the patients were responder according to do activity uh
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endpoint and for those question what expensive less degrees instead disease
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you have less a responder according to the to the to the activity in point
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once again suggesting that a significant decreases that is is is associated with a significant decrease in activity
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the problem is that it has not been comfy on you know
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on the study that put three different study about therapy doesn't versus placebo
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here you have the results in the in the bible doesn't pounds in in the there
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is is in the placebo arm those patient to achieve a high degrees instead of these
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those patients who didn't achieve a high decreases saturdays and the rates of response according to the activity
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next was the same so decreases that this was not associated in the study is a decreasing activity
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so how can we do in as a way uh we can
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derive some more than try to model the evolution of the disease activity
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this is the purpose of this uh study once again the the the the find the printed the thing trial
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more than two hundred and eighty patients we spell either biopsy at the beginning in at the end
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they they try to find what where the power
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mittens that why independently associated with a decreasing activity
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so they find that the the treatment was a associated with the 'cause activities because
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practical traverse positive the baseline ass baseline to decide the buys line i a now
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that buys lines although i mean is is and they found also very simple things
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but to degrees in the l. t. higher than seventy eight
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you need a leader was a strong project or of decreasing activity
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here you can see that the audrey so why higher than ten to combine
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all these parameter in the signature in the in the in the in the model
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in this little either very good or rock zero
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point eight for predicting decreasing activities so treatment response
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you can send a graph here in the blue you have the patient data as a correctly classify at
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in right does that way um but great because if i had and you had
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a seventy seven percent great production using this parameter to predict response and the therapy
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so this is possible things to quite simple parameters and we didn't know
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that he l. t. degrees was the strongest parameters she did was response
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so we had also try to move to others i can set you know
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that most of the face to be in phase three trials include patient with nash
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a significant activity an essay oracle and four and a significant amount of fibre
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is is f. to industry we don't have them as if this flash today
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we have to test for advanced fibres is but they are not so good to dine those earliest stage such as i have to
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so there is a problem to identify decisions need to be included in clinical trials
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that's why it's some test has been developed specifically for this dynasty baguette
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uh it's in french sorry a figurative nash so now you have three
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test did you get it for details to to get the news for
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that included getting will be in your fight remarkably green y. k. forty
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in a a macro right this test is uh the vote by gen fit
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we have developed the max three that combines you might banks yes the instigating
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any cause us as developed in alaska graffiti a test that combine stiffness and got resort entries i mean is it
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so this test they they get a diagnosis
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figurative match which is the inclusion criteria interpretive trials
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and what is interesting indigo then uh in the button study you can
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see that they well a close relationship between the evolution of the news for
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of gen fit and the abolition objectivity when the activity goes down that
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this goes down when did you guys that to discuss that so the test
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that was designed to include the patient in the clinical trial so to dang those disease
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was also very interesting money to all the disease evolution and the therapy
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and will present at the next uh a compressor of the european association
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similar results between the evolution of the max free and uh and you have a vision
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of uh the activity uh it's not in the therapy it's letters really special perspective a biopsy
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so finally it's like the concept of the greedy get the mobility in of the battle budgets
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you have a test that gives you the dynasties and then you just need to follow its evolution when it all the treatment response
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that would be very nice but we need to actually data definitely prove this uh this concept
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so i have spoken a lot of disease activity a two point degrees in the mascot
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but this is not the endpoint recommended by the f. d. a. in the in the
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remember that the twin points on nash resolution without washing fibres is
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and five resist regression so we need we need to put a
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false to be able to know that you really diners these twin point
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because these two endpoints are required for the conditional approval of drugs and
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we require those when can contract is to money thought the disease activity
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so i show you she i unfortunately the results of
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the study that where quite positive for uh the monitoring of
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this is activity with the decrease in two point of an escort when you consider natural position there is no difference
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no association between to decreases that was is and the rest of patients which even s.
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resolution eight is consistent about all the studies that evaluate duration should beaches deposition nash resolution
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so how can we do not so much data what we know coming from the friends that he that
00:19:19
is evaluated the evolution of the by you marker and the correlation between a non was programmers from the last
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you can see here that surround reasoning is is once again are very useful marcus
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we have a much more degrees in haiti in the responders compared to non non responders
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in here for a yes the that was really interesting because those were numbers although there was
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no moving of the u. s. d. but interest for the other was a huge degrees in yes
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and it was also found a exactly the same results in the tonic study does evaluated the
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bit i mean even uh in the in children we can see that for those patients who improve
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uh there are there divisions and uh and uh and
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nash we have a much more degrees in some percentages
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but maybe not finally die knows it's very difficult but
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to money toward very simple parameters could be very useful
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and i'll regression of your fibrosis which is probably the
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most interested in point because if there is reversion of
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fibres is on the progression you can assume that you want another version two services and you're at the competition
00:20:31
so we are there are extensive results to find new by you
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marcus special you hear the process really a matter of a fibre cases
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here you can see a very nice correlation between the the level of the of the of
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the process three and the different fibres stages and there have these uh you have this study
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uh showing that we spell liver biopsy is not treatment response it's evil
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biopsy and then give about c. l. format so it's more natural history
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when you have an improvement in uh in fibres isn't of a biopsy of new programs and process we
00:21:09
and when you have a a while sinning of also worsening of
00:21:12
the market so the buyer marco is able to follow a disease evolution
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ops the reasons sticks sorry uh i need to go back
00:21:27
tuesday i just want to show use that so um the idea of the as you dine this
00:21:34
is only the fibre is is is to combine directorate single buyer marker to even more increased designs detectors
00:21:40
so now we have panel that are very well correlated to the fibres stage in cross sectional studies so naturally
00:21:47
because they are calibrated unbelievable and the lever fibres is we want to evaluate their ability to follow the disease evolution
00:21:53
so here are the results of the national study present
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at the the last the e. us a meeting uh
00:22:01
any does the abolition off the fibre test according to
00:22:05
treatment response here you have the special when profile was
00:22:09
here you have those patients wa stable in your those patient wilson look at the principal group yeah the the the
00:22:16
white circle it's quite logical when you have a worsening
00:22:20
of fibres is you have a worsening of the fibre test
00:22:24
well you have no jennifer with stage the fibres this is quite stable
00:22:29
and when you have an improvement it is also stable so what quite logical
00:22:32
but when you look at the treatment arms you have always a decrease in the fibre test
00:22:39
so you have a total disconnection between the test in the evolution of evil fibres is
00:22:45
so i want only why is there any interference
00:22:49
between the drug mechanisms action in one of several
00:22:54
parameters of included in the in the fibre text
00:22:58
and i found a study it was the i found this
00:23:01
to be a where they explain in vitro that act ethics activation
00:23:06
directly suppress the production of it probably putting
00:23:11
in one which is including the fabric test
00:23:14
so thanks to this paper we can assume that if you use a fix are going east
00:23:19
you will have already got three degrees nepal what anyone and evolution of the fabric test is not
00:23:25
evolution of fibres is much more much more target engagement finally
00:23:30
but it was a nice reasoning but uh thirty fours because if
00:23:33
you should press uh people putting in one the fibre test infected increased
00:23:39
in in the in in the in the in this is that you can
00:23:42
share the fate degree so it's a good idea but it's not the good answer
00:23:45
so i would be very interesting to see the evolution of the different parameter
00:23:50
including the fact that there's the type understand why there is always a degrees
00:23:54
but yeah id and the message is that when you evaluate the buyer marker
00:23:59
even life you evaluated by their that include several by america you need to be sure that
00:24:05
the by america include in the test up totally independent of the mechanisms of action of the drug
00:24:11
if not you will major target to gauge events rather than monitoring to disease evolution
00:24:18
so jeff you have the seem to demand
00:24:20
a study which shows how it's complicated finally because
00:24:24
in the at three patients you at twenty percent progression to services and you've already the difference
00:24:31
that yeah that's got news you're at baseline was predictive of the progression of the disease
00:24:36
and the the abolition of the yet if was also productive
00:24:40
but when i try to derive a model that combines both yellow
00:24:44
if at bass line and the evolution of yellow if during the treatment
00:24:49
it has no much more uh accuracy than the yet if the loan
00:24:53
at baseline and finally the abolition of the l. f. as no information
00:24:58
so probably we can have some uh explanation and shop them
00:25:02
follow a not so much um uh events to to study but
00:25:07
this study shows that how it's difficult to predict the disease evolution things to test
00:25:13
that they've been developed for the diagnoses of division and not the monitoring of the disease
00:25:21
now let's move to end after buffy we have also data
00:25:24
for after buffy so uh the fibres get in the regiment study
00:25:28
not so bad finally because it seems more logical than the uh with the fibre test
00:25:34
she yeah when you have an improvement of abuses stage we
00:25:37
have a slide degrees in the fibres can whatever treatment owns
00:25:43
well it is stable fibres can is the well in when you have a
00:25:47
a name it was single fibre is is you can see that there's a trend
00:25:51
for a devotion the of uh of uh well solution of the fibres can
00:25:55
the problem with the fibres can is that we know that there is a a liability the measurement
00:26:01
when usually the stiffness is one guy then you took another guy the
00:26:05
senders among the same passion to meet after you have twenty five percent difference
00:26:11
so this is a huge variation that probably impairs the ability of the
00:26:15
device to press is when it all this is uh this is evolution
00:26:19
so we need to actually deeper to see fibres can is really accurate to monitor this is the third
00:26:27
you have also and there i met databases published last year and
00:26:32
write these match accurate than the the the the fibres can to diagnose
00:26:38
uh give a five is is so is it more able to monitor i was just evolution
00:26:43
so we have this study published last year uh
00:26:46
coming from the simply maps to the small sample size
00:26:50
forty five a patient only with the magnetic resonance uh scruffy at the beginning it at the end
00:26:56
once again we have a nice correlation between every right and the fibres is stage only the biopsy
00:27:03
so i mean right is a good a marker diagonals in cross sectional studies eva fibres is
00:27:10
and when you look at the fibres this evolution there was no more significant difference between
00:27:15
the evolution of the delta often arrive in between the station were responding and those were not
00:27:24
so i feel a though disappointed because all the results are negative
00:27:30
so how can we do once again i come back to the study from the
00:27:34
log on as remember the study with laughter modification swindle patients believable see before and after
00:27:40
uh they try to as before fall uh oh but you can you can see the try to develop a
00:27:45
a model to predict uh the um the uh the yeah the evolution of a of a of fibres is
00:27:52
so they found that the the the product or of uh of fibres is a improvement
00:27:58
where the uh division of that effort fibres corrugated mobile be missing resistant weight loss
00:28:03
once again the platte let n. look at normality at the end of the treatment
00:28:08
so once again simple parameters gives you very interesting information if an ominous kitty at
00:28:14
the end of the treatment you have been form or a chance to achieve fibres improvement
00:28:19
to combine these parameters let let's get a remote
00:28:22
levine yell teams of evolution during uh the the trial
00:28:27
and they found a very nice thing it sure is a very good or very good discrimination between responder and then respond
00:28:33
showing that it is possible thanks to the monitoring of simple parameters to evaluate into
00:28:39
money doctrine first points so we need first to body this finding in other studies
00:28:45
and probably maybe i don't know that uh does
00:28:49
nature will not we will be a a specific
00:28:54
often i stole modification i don't know if it will be exactly the same with on the subject
00:28:59
um with a drag the uh it depending on the make a
00:29:02
vexing remember that we say that the marker needs to be totally dependent
00:29:06
of the drug mechanisms of action we have many many many many many drugs to probably it would be difficult
00:29:11
to find a single buyer marker able to evaluate division of uh of the divisions uh for all the jets
00:29:19
and i would like to finish once again with the with the optimistic uh
00:29:24
uh things and a very simple ideas i go back to the regiment study
00:29:29
improvements table was indicative of fibre is is a very simple by marker the fee for use
00:29:36
d. let let's in age and you can see i i i think this feature is very nice
00:29:42
it is very simple parameter fibres is improve all goes down
00:29:45
for buses table or just it'll probably this was an all wilson
00:29:50
so we're thinking about magnetic resonance imaging about present it
00:29:53
as the referee combination process freeze very complicated by your market
00:29:58
this is really interesting and important to evaluate this but mark uh but you know that
00:30:02
somehow marker that are very uh simple that
00:30:06
i've been a ejected from the dying those
00:30:09
is because they're not very well correlated to the division when you more little the dizzying
00:30:13
when in fact we evaluate the evolution of the since the treatment to become very informative
00:30:22
oh and uh i would just to illustrate my
00:30:25
thinking if that thanks to the phase three clinical trials
00:30:30
with the long term follow up very close monitoring often and
00:30:34
if test in the buyers you going to serve a few parameters
00:30:37
maybe that we can change our mind not to try to
00:30:41
uh find somebody marco correlated to the is the vertical response
00:30:46
but to look at the trajectories of the buyer market during the for
00:30:49
up and try to find which one is directly predictive of the outcome
00:30:54
we are still very uh close to leverage the a. g. we know that the in points to the oh is that what you call
00:31:01
we try to develop by your marker that are radical related to do is to the g. but
00:31:05
remember that we should use the g. because it is a surrogate marker of the outcome of the patient
00:31:10
if we found a new value marco able to predict the outcome we will have
00:31:14
the final did did you get the mobile been of the of the about the ridges
00:31:19
and this first free trial we'll give us the answer because we'll have thousands of patients
00:31:24
close monitoring and we'll be able to show which by america which evolution on
00:31:29
the therapy is correlated to get come in just a predictor of good response
00:31:34
as finally it does vary the done very nicely in uh in c. d. with the globe school
00:31:42
so this is a highly relevant topic nervous where marcus of
00:31:45
response to intervention because uh in the still of a coming
00:31:48
doesn't make a pact is we we need to evaluate if you can see of the treatment we will give to the patient
00:31:54
i was like accuracy is not the same that ability twenty
00:31:57
per treatment response in super parameters give you very interesting information
00:32:02
but in fact we have tons of kitchen as i show you the data that are available now not so much
00:32:07
we need to accumulate a new new data so there are a lot of exciting work to do thank you so much
00:32:20
thank you don't you're really putting line some quite important concepts ah that's we have to remember yep
00:32:28
little wages for you talk but i would like to know what
00:32:31
what are you thinking sewn easy view developmental piecemeal by omar trips
00:32:36
you can do a mysteries in in animal models rather than humans there's
00:32:42
you know the the evolution you much take years and handles the bonds
00:32:46
so probably you give you can extrapolate from from animals to men
00:32:52
probably you could discover by about this much weekly in animals than men
00:32:58
that's very interesting uh a question i would trust i would stress in my own marker
00:33:05
are developed in any maps for fibres is because the story and on on it show that
00:33:11
when you find by my cousin my forefathers is you will produce the results in humans
00:33:16
for information is is not totally the said i think that for information uh animal models uh no
00:33:21
well designed to find value marcus it's much more difficult because it not not not totally new big
00:33:27
information in the process of of of uh um the not meaning
00:33:31
to be the region from so it's not exactly the same contacts
00:33:34
so it's difficult to express what for fibres is it's close to use in the evil is a lever questions so okay for
00:33:40
information it's quite much more complicated we need a really a an
00:33:44
animal model that mimics the different ages and we don't have to
00:33:54
the question no no no question
00:33:58
because you know a good way to improve your twins i mean is is is to lose weight but right so
00:34:05
um actually you showed us first that's weightless isn't important predictor
00:34:10
and then you set transmit is is is an important predictor
00:34:14
actually one had something to the other which is the same thing
00:34:19
this is a very interesting question but i wouldn't so with the russian rates
00:34:23
that age you have an effect on frozen noises but not so much weight loss
00:34:27
so i think that was i mean is is itself disinformation it is not a matter of weight loss
00:34:33
are you sure that also you have the response a manager last night
00:34:38
when you look at if you have comments if you show that factory weightless
00:34:41
with not so much but it's your response but was and is that right
00:34:46
but then it could be interesting because you can measure transcending is uh
00:34:50
early in the tree now you can look at that after three months
00:34:53
and say maybe we can put you can't stop you can have some stop who's in trials me
00:34:59
yes what is interesting was anonymous it by our market it that you have always and only response
00:35:06
i never seen a buyer marker that a failed after one year of treatment
00:35:11
usually i even for fibres is you know the processes of hydrogen is isn't fibre is this
00:35:17
the the fibres is is at the end of the
00:35:20
of the process decrees fibre janice is fibrous is 'cause that
00:35:25
so you have degrees in the situation of the protein the fibres use in increasing the but
00:35:30
the removing of the metrics and then several months after you see what happen only for biopsy
00:35:36
so if i was this is really a late in point
00:35:39
in using by marco you see very well the singers that
00:35:42
is we re interesting to have a an idea of uh of the response uh after few a few time and it's
00:35:52
thank you from the
00:35:55
yeah
00:35:57
one major point that we have in this field is
00:36:00
that we still rely on a compatible which is imperfect
00:36:04
because we rely on the complies with the the biopsy we'll know that there are some time settled by ups
00:36:10
one of the positive aspects only basic methods it that at the end
00:36:14
that could be in some asian reflecting the reality that we do not
00:36:19
see really but by c. so i think in the steel what we need and we don't have it you to a matter of time ease
00:36:26
what happens to patients as for outcomes and all
00:36:30
these outcome really to to learn basic markers not just
00:36:34
for for response but also for clinical events of individual keys to do you think we will have some
00:36:41
news in the sense in the next few tour from from the studies that build only in the last ten years
00:36:47
mm with me in the sense of looking back there at
00:36:51
the natural history of the disease in relation to really basic markers
00:36:57
the problem is that my opinion natural history
00:37:01
is not the same that and treatment response
00:37:05
you can have some by remark about our work related to the not first
00:37:08
to me when when put to drag just up you can distill this relationship
00:37:13
and a good buy a marker could become to the in not informative so i think
00:37:17
that we need the prospective longitudinal studies we
00:37:22
under serve me is repeating deserving showing that
00:37:25
we are able to predict the outcome of patient and the server p.
00:37:29
and if the if clearly the phase three trials want them for uh we give us helping indians up
00:37:42
thank you wonderful presentation in santa we that by marker are
00:37:47
the common from clinical trials because that i could mark alfredo sees
00:37:53
should be it to oh all the stages of like
00:37:56
roses provides the right one next to a three and four
00:38:00
well see yeah all those trial error rates the left to have three and a four oh not too
00:38:04
bad we don't have to see wrong and then there are legal in f. one cell what do you think
00:38:12
is it going to attract the yeah the unreliability of display marker
00:38:21
ah i we have made a lot of
00:38:27
a false dying those being very dynasty targets
00:38:33
i read all the finance fibre test yet it task or fibre better
00:38:39
it's a a mathematical model and that gives you the probability of having a a
00:38:45
dynastic talk it so i've usually the bridging fibres is that's just a no forms
00:38:51
and we we we wanted to be even more increase the diagnostic accuracy
00:38:56
i think that for treatment response that two possibilities
00:39:01
i said the test you have developed are able to
00:39:04
follow the disease because they have been calibrated on the evaluation
00:39:10
but the first result shows that it is not so simple
00:39:15
we can continue in this direction to evaluate him to see your with
00:39:18
a high number of patient was much more events we can find better
00:39:21
correlation because all these results are very preliminary and do the the comes
00:39:25
from varies very small studies all the other direction and i think it's
00:39:31
you it will and like that we need to go back at the beginning in
00:39:36
to look at the in d. v. d. you have by you marker one by
00:39:40
one and find which one is well put forth as though if one of two
00:39:44
three no the idea is to predict the outcome in it is not the same question
00:39:51
if you look at the people are published from uh you and who in the uh the
00:39:55
the us registry there are a little impatient
00:39:59
with nash and how i'll call to predicted yorker
00:40:02
also reverberated complication in h. t. c. wheeze certain percentages let let i'll be mean and there
00:40:09
was a variable calibration between the model and the outcome my opinion is that it's a concept
00:40:16
the various to g. e.'s like uh uh uh uh this and we drove
00:40:21
it's like it's like a groovy you decide that's or is this is a circle
00:40:26
and you decide that bridging fibres this is a like some sept ah that goes the how the bottom tracks
00:40:32
and when you have a circle it's at four so we try
00:40:35
to find the correlation between natural parameter so some proteins in the blue
00:40:40
the speed of the sure way and some uh some uh ah picture around a a
00:40:45
a scan that we have design from uh had the operation can that be the perfect
00:40:51
so we can make a lot of effort to find new um and more and more accurate models
00:40:55
but uh does not the question she we don't want to find a a correlation between
00:41:02
natural things and the architectural vision of that even we want to
00:41:07
woo to evaluate it would the the the promises of the patient
00:41:11
and we want to correlate the buyer market now with the outcome which
00:41:15
is not the same in when you move to die from diagnostic to proposes
00:41:21
all the papers show that with very simple parameters you able
00:41:25
to have a very nice production it is not the same question
00:41:31
yeah
00:41:34
i raise a kind of this question
00:41:38
and by thinking that probably uh we a little bit
00:41:43
confused and the feel of flash or whether we're talking about
00:41:48
well i mean we all know what we're talking about that when we define what should be our our eighteen
00:41:55
then the difficulties there yes i've been many people it is the
00:42:00
you're looking at that point out of the labour other and we
00:42:03
uh uh looking at low cost tolerance other looking at the roses
00:42:08
but no one is looking to a disease that you specifically
00:42:13
define that we know very little about that but the physiology
00:42:19
of of uh of mash has to be attacking the fundamental
00:42:25
so from a practical point of view it would take another at it and
00:42:29
i would say well let's for that we don't like that component of the disease
00:42:35
probably the bail marcus that that would force approaches should work
00:42:41
as as well it's other projects and we're good at predicting outcomes when it's it's very advanced
00:42:49
yeah that would that would basically that that we we say all these libraries
00:42:55
that that comes only cam that the that says stages
00:43:01
but as for the other components of the of nice which at the kind that that's right
00:43:06
with all the components probably we ought to go to what is used to
00:43:11
in the chronology and get the vascular disease so i i agree that it's
00:43:19
uh what the score work of the allergies that would for the chronology is
00:43:23
that good for that but that was the simple score that takes a bit
00:43:29
if not we can please the situation that happened to get us
00:43:33
credit diseases and say well we asked the there with the kids
00:43:36
look at the last whatever is good you know that the patient i exactly the same but they like lace
00:43:43
they they list from my credit for that day that from a service rather
00:43:47
more it's so probably it's it's if it's in in job probably could be fertile
00:43:53
some treatment that doesn't look at that patient outcome but at these cool
00:44:00
i i i see that they're facing kind of these when we are looking at nash in every match
00:44:11
everybody say it's it's it's not important to treat because they don't like it so it for that
00:44:18
in in that they get but snatch that it thinks it
00:44:21
rogers and probably is when the civil just component is very important
00:44:27
the bible is probably more important than that we're speaking about trying to trying not the liver disease but
00:44:34
the metabolic disease as a war concept but i would say that basically it's nice when that let's see here
00:44:41
take up more probabilities of dying from the cut the best that i made a lot of
00:44:45
components that probably the disease so probably if you read the the little will not be pretty
00:44:51
if the patient is t. t. c. b. at that fits zero g. when huh the risk of they from that it's much
00:44:58
more important and in each one so i even that they should have to make up or not is not recorded it but it's
00:45:06
it to look at that and it does that reflect
00:45:09
the probability that these disease really influence you live up
00:45:16
but you can also imaging a a situation where you
00:45:19
have a funny question we have a question for congestion risk
00:45:24
uh you develop a question for the the the lever risk and then after you
00:45:28
choose the drag that best fit with the the problem is is of your patient
00:45:33
because as shown by uh is it is that you have some drugs dedicated to leave out that are also i've metabolic provide
00:45:40
we have we will have drug with different mechanisms of action in with different uh uh possibilities
00:45:46
according to the profile depression can can match and probably personalise missing
00:45:50
as a it was said the four of the e. only one
00:45:56
so you need to do a lifestyle intervention together with it in that it is it there
00:46:01
they have it again but if if if they have the best love this is is present
00:46:05
and they did it puerto separate it is present you you
00:46:09
would look at one thing that it's magic and cute is
00:46:17
a very moralistic we looking at the disease process uh_huh uh_huh uh_huh uh_huh
00:46:28
other comments questions
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