Researcher comment: The SPIRIT-P3 study | Laura Coates

Researcher comment: The SPIRIT-P3 study | Laura Coates


[MUSIC PLAYING] So the SPIRIT-P3 study which
I’m presenting here in ACR is a very novel trial
design, and it’s looking at withdrawing drug in
patients who have done well. And it’s one of the first
large-scale withdrawal studies that we’ve seen
specifically in PsA. So these were patients who
were treated with ixekizumab. It was open-label. They knew that they
were getting the drug. And then, if they reached MDA,
the minimal disease activity criteria consistently
for three months– so on four separate occasions
each four weeks apart. Then they were randomized
either to continue on the drug or to switch to placebo. So they then didn’t know
what they were receiving. They were randomized
from that point onwards. So they’d been on the drug
potentially up to nine months. So obviously people achieved
MDA at different times after starting the drug. But then they had it withdrawn. And what we saw is a very
high relapse rate in patients who were withdrawn to placebo. We saw some relapses
in the patients who actually continued on the drug. So there are two possible
explanations for that. One is that, obviously,
psychologically they were concerned that their
drug had been withdrawn– that might have affected some
of their patient reported outcomes. And also there may have been
just a bit of natural variation in their states. So if they had just
achieved MDA and then maybe lost control in one
domain, then that would have counted as a flare. And then the follow-up
part to the study was obviously to
give the drug back to people who had struggled. So as soon as people reported a
flare and lost their MDA state. Then they were
eligible to go back onto ixekizumab– and nearly
all of them recaptured very quickly. So we know that
stopping the drug completely is very
risky, that we’re going to see a high rate of flare– up to 90% for patients
who were left longer. But if we then get
them back on drug, they stand a good chance of
recapturing that same disease control. I think that this is
helpful in taking us forward because this kind of
study has never been done. It’s a very different picture
from axial spondyloarthritis. So in axSpA, we see that some
patients can withdraw the drug and actually stay well– but in PsA, they really can’t. These patients who admittedly
have more severe disease– they’re at the severer end of
the spectrum for the patients that we see, but you see
a very high relapse rate. So I think it would put us off
doing future studies like this, where we stopped
the drug completely. I think where we need to focus
our efforts now is on tapering. So we may not be able to
stop the drug completely. But we’ve got a number of
smaller observational studies which suggest we can probably
taper the dose in patients doing very well. And then we can minimize
any risks from the drug, save the costs, and
keep people well. Through the additional analysis
that we did on the same study, we’re looking at which
components of MDA actually caused the flare. So when we’re thinking
about patients in MDA, there are seven
different domains. So there’s tender joints,
swollen joints, enthesitis, skin pain, global, and HAQ. And any of those
components losing control could cause a loss of
the MDA criteria overall. And so we looked
at which components tended to be associated
with the flare. And actually we saw a difference
between drug and placebo for all of the components–
except for HAQ and enthesitis. So I think the HAQ makes sense. We’re not seeing
such a quick change in somebody’s functional status. That tends to be
a slower change. But we did see some patients
who flared with tenderness, some patients flaring
with swelling, some patients whose skin flared,
and some patients showing increase in pain
and global scores. So it was really
different disease activity across the board, when you’re
comparing those who continued on the ixekizumab,
with those who had it withdrawn and
switched to placebo. [MUSIC PLAYING]

Leave a Reply

Your email address will not be published. Required fields are marked *