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Short- or long-term denosumab therapy? Part 1
Dr. J. Everts-Graber, Bern
Friday, May 13, 2022 · 1:37 p.m. · 15m 22s
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00:00:01
good afternoon i guess it's on so thank you very much for this kind introduction and
00:00:07
the invitation i'm glad and on or to be here and discuss with you this important
00:00:13
question should we treat our patients with short or long term tunnels amount
00:00:19
i doubt we'll start is the bait by advocating shorter than other map treatment this
00:00:28
so the northern map is a unique and very potent anti resulted agent
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in contrast to this falls funny it leads to
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continued p. m. d. increases for at least ten years
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and during this time it reduces both vertebral ends known vertebral fractures
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we can even up so if the other reduction of nonverbal fractures
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in the long term use does this however continued low and not
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aggressively declining fracture rate you wanted three years of then also map therapy
00:01:04
but still this efficacy of the northern map
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that appears particularly in the longterm use raises the
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question why shouldn't we benefit from this and
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treat our patients only with the shortest another maturation
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and in the next couple of minutes i will give you for arguments
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why you could consider short duration at least in some patients or some situations
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and i will start with the question what are
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reasons to discontinue then also map because after all
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osteoporosis is a chronic disease and mostly needs a lifelong treatment management
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and we usually discontinued and also map and switch to another therapy
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if our patients have side effects or adverse events or are
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they have a evidenced treatment failure but all of which is rare
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but we also stopped therapy in general when we cannot expect for the treatments benefits
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and and analysis of freedom extension trial data showed a clear relationship
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between the total hip t. score g. if while and then also map
00:02:18
at the sub sequence you one here fracture risk and
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achievements uh bob it totally hip t. score of minus one point five
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did not for the reduce the fracture is and
00:02:32
this was independent of h. and prior nonverbal fractures
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so in this situation we should strongly consider to
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discontinue the northern map switch to where p. p. therapy
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not just for patients saved can cost reasons but also
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in the light of the diligent provision of health care
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my second point is actually not an
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argument against along third term therapy does rob
00:03:02
precondition for it it is crucial that our patients are adherent to dan also map
00:03:09
and this is particularly note where to because we prefer ripley treat
00:03:14
our eldest and frail patients with long term or even lifelong bundles amount
00:03:19
but we know that goes in the lays off already forty six week
00:03:24
can lead to an inadequate b. and your response and then increase the risk of vertebral fractures
00:03:31
and all they we know with that get hearings to parental medication is generally do it
00:03:39
i think it can become critical when our patients i'm moving to a nursing home
00:03:43
because as you know with the parental and just uh projects every peak
00:03:47
israeli on the medication laced and never in the pills organise rubber patient
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so every uh well study of two hundred
00:03:56
post menopausal women showed that about fifteen percent
00:04:01
how did elaine get using and nearly whole fifteen experience the vertebral fractures
00:04:07
so the mean age of this stuff study population was seventy five he's and they
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were all persistent with therapy so they had the maximum closing delay was three mom
00:04:19
and this risk of vertebral fractures may be associated with they didn't also
00:04:24
map treatment duration this has been found in some but not all studies to
00:04:31
my third point is closely related to the
00:04:34
risk of dozing delays it's the rebound effect
00:04:38
so the rebound all still classed activity off to
00:04:42
the northern map leads to increases of bone turnover markers
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highly above prix treatment levels and this leads to a complete loss
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of being d. gains within one to to use and in
00:04:55
the spirit we can observe him at increased risk of vertebral fractures
00:05:00
and meanwhile we know that we can meet a cage this rebound effect
00:05:04
with sub sequent peaceful so need therapy and solitaire nate is the most
00:05:09
widely studied agent didn't in randomised clinical trials
00:05:13
but still many of our patients experience a certain bone
00:05:17
loss often also map despite subsequent this also like therapy
00:05:23
actually is to get a we analysed the risk factors for the bone loss
00:05:29
in a retrospective observation or study of twenty twenty post menopausal women
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yeah i received another map for one to five years
00:05:38
and most of them also with a sequence peaceful snake therapy
00:05:42
and two years later we assess the fracture rate and being d. changes in these women
00:05:49
and we found that younger age below were body mass index
00:05:53
the absence of a prior peaceful sweeney therapy to be and he gains during then also map
00:05:59
therapy but also didn't also map durations were
00:06:03
associated with increased bone goals often also map and
00:06:09
this observation with the longer than also marked duration
00:06:11
as a race factor was also found in prospective studies
00:06:17
so i'd like to show you this figure this this and
00:06:20
that b. m. d. evolution of two groups of patients patients
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who received an also received five tunnels map injections and sub
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sequence is false one eight so it was mostly solitude eight
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these are in black and those who received ten
00:06:35
than also map injections and sub c. compass falls funny
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and you can see that goes with ten injections they had higher higher p. m. d. gains
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on the ferry people also increased last off to bits and off to six to eight he's
00:06:50
the b. m. d. was comparable in these two groups
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the same applies for the total hip and this figure
00:06:59
reminds me off the famous you you with fact right
00:07:02
that's not pointing losing a lot of weight and then very gaining it again within a short time
00:07:07
the key point is to maintain the health your weight or health european d.
00:07:14
the baseline directory sticks between these two groups showed no
00:07:18
significant differences but still it was just a retrospective observations
00:07:23
but just a few months later marcus and colleagues
00:07:27
may very similar observations in the prospective multi centre study
00:07:32
so they assess the the and bone loss of fifty post menopausal
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women who were exposed to the northern map for one to five he's
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and all of them received one sub sequence solar donating fusion six months later
00:07:48
and then he says that that b. m. g. m. t. bone turnover marks when you use later
00:07:55
and these these ready to study group so patients who received less than sex
00:08:00
than all the map injections and there was received more than six injections and
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those with the longer than also map three twenty had
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a lower body mass index and the higher prevalence of
00:08:13
uh of fractures at baseline so basically a more severe osteoporosis
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and now while select an eight was able
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or efficient to preserve the bone mass gains
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at the longer spank in patients with less than six another map injections
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this was not the case induce with along with an awesome duration
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and also with they found highly significant correlation between the northern map
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injections and the bone loss posting also map at the longer spine
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not attitude leap to but in our
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aforementioned retrospective study we also found significant association
00:08:58
between didn't also maturation and t. bone loss at total hip
00:09:03
as well as with bone turnover marker so basically every band itself
00:09:10
and overall our patients who received an awesome half of one to five he's
00:09:16
i just of sequence originated therapy they had lost
00:09:20
about thirty percent of being d. gains at still
00:09:23
longer spine and about fifty percent i choked leap
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which is probably even more did detrimental to our patients
00:09:31
and an extensive research is now on going in order
00:09:35
to maintain the b. m. d. of the ten also map
00:09:40
but still we are not sufficient in preserving the b. m. t.
00:09:44
so i'd like to show you shortly this this study and
00:09:48
sophie stalling and cool leaks and analysed to bone loss in
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sixty post in sixty patients who were exposed to uh
00:09:57
the northern after forty five years and then they were randomised
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to receive step sequence alternate at three different time points
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six month off to the last another map injections nine off
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and the group who receives originating case of increasing going to new markers
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but in all groups the patients experienced a significant bone loss
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both at the longer spine and to total hip your respective
00:10:27
of the timing of the frequency of sub sequence alternate
00:10:31
and these were very important findings for our for ross clinicians but still a bit frustrating
00:10:38
and now many studies now are addressing the question of how to maintain to be empty
00:10:44
and while we're waiting for more every vince i show you would we do so i think most of us do we
00:10:49
give the first solid turn eight six months off to the
00:10:53
last another map injection and then we check the bone turnover markers
00:10:57
and if we can it's a a relevant increase so in our thing
00:11:01
to write a two fold increase we re administer a second semester need infusion
00:11:07
and then we can see those who receive does that console t. bone turnover walkers decrease
00:11:13
okay but i'm not sure if this is us march timing of the second solo journey because
00:11:19
when they want to know who marcus are increased twofold to boone is probably already lost
00:11:26
as the deportation productive college in the back
00:11:29
to cross laps somehow reflects to poodles particularly
00:11:34
in a woman who had a complete suppressed bone turnover with just a few months before
00:11:40
and two additional comments these factors all in switzerland it's off label so
00:11:45
we have to make sure that up patients are getting digs this reimbursed
00:11:49
i'd these fat consoles in the rebound or often not very
00:11:53
well tolerated so we have to prepare our patients to this
00:11:58
but still hopefully we will have soon and efficient and feasible
00:12:03
management off the long term than also map because because then my argument with
00:12:08
every band will become irrelevant but i still have a fourth and last argument
00:12:14
for a short and also map therapy at least a very short one
00:12:19
it is a well documented assumption that the bone turn who would does not
00:12:23
re bound off to one maybe even not off to to dan also map injections
00:12:28
and that's also the reason that many studies of that helps
00:12:31
to be banned or excluding patients with only one or two injections
00:12:36
and so did we but when we looked at these patients two yeas ago
00:12:40
we observed a surprisingly high b. m. d. again
00:12:45
in the other who's received one then also map injection and subsequent is false funny
00:12:50
that was the reason that that we intentionally treated some patients
00:12:54
in the last two he's with these short street in sequence
00:12:59
and i want three just table this is the overview of all sixty one patients
00:13:04
who received want another map injection in our study population but i will focus now
00:13:09
on the thirty two patients who received one then also map one solution eight six
00:13:14
months later and then we check to b. m. d. and t. bone turnover mortars
00:13:19
one year later and these patients experience to be in the increase off almost
00:13:25
eighty percent at the longer spine and between three and five percent at the hip
00:13:31
and also to p. one and p. decreased significantly in this time
00:13:38
and of course this is just a retrospective observation it cannot prove treatment if
00:13:43
it is yes this would require around the mice control study design but still
00:13:49
this could be an interesting option for some situations for example
00:13:53
younger perry menopausal women with high bone turnover or at risk for bone loss
00:13:59
but they have not a very high fracture is because they are
00:14:02
young and these patients could benefit from this short intervention who would
00:14:08
that would mitigate the high bone turnover every salt in it b. m. t. gain in a short time
00:14:15
and the long term than also map therapy could still be administered
00:14:19
relate to when they are older and at higher risk of fracture
00:14:25
so
00:14:26
i gave you for arguments for short term duration so we should consider to discontinue then also map
00:14:32
if our patients reach the total hip t. score of minus one point five
00:14:38
with the short term than also map we have let probably less problems
00:14:42
with it he rinse we have a less pronounced bone loss often also map
00:14:47
and who knows tunnels them up all for short could be an interesting treatment option in some patients
00:14:53
but after all and this is my most important message choosing the optimal then also map
00:14:59
duration is always individualised treatment decision that we
00:15:04
make together with our patients thank you very much
00:15:17
uh_huh
00:15:20
what
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Short- or long-term denosumab therapy? Part 1
Dr. J. Everts-Graber, Bern
May 13, 2022 · 1:37 p.m.
401 views
Short- or long-term denosumab therapy? Part 2
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Clinical debate: Short- or long-term denosumab therapy?
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