Discussing the guidelines for managing psoriatic arthritis: Part 2

Discussing the guidelines for managing psoriatic arthritis: Part 2


[MUSIC PLAYING] INTERVIEWER: Hello, and welcome
to this Medicine Matters podcast. Recently, the American
College of Rheumatology and the National
Psoriasis Foundation released their first
evidence-based guidelines for the management of
psoriatic arthritis. In the second of a two-part
series on the new guidelines, we spoke with
Professor Dafna Gladman from the University
of Toronto, Canada; Professor Philip Mease from
the University of Washington, Seattle, in the USA; and
Professor Oliver FitzGerald from University College, Dublin,
Ireland about the implications of the new guidelines,
the limitations, and key research trials
in psoriatic arthritis. INTERVIEWER:
Firstly, Dafna, what implications will the
new ACR guidelines have on clinical practice? DAFNA: So I think that
here the relevance is going to be on the site. In the United States, many
rheumatologists already are treating patients
with an anti-TNF agent as a first-line agent. In other jurisdictions, it may
not have any impact at all. DAFNA: Because for example,
where I practice, in Ontario, Canada, I cannot give an
anti-TNF agent to a patient with psoriatic arthritis
unless they have failed both methotrexate and leflunomide and
they have five swollen joints. And I know that in Britain
it’s the same thing. They have to go by the
NICE recommendations, which allow them to use an
anti-TNF agent after failing methotrexate and leflunomide. INTERVIEWER: And Oliver,
is this the same in Ireland and other European countries? OLIVER: No, quite different. In Ireland, we can use whichever
agent we feel is appropriate. And that would be the case in
many European countries as well that wouldn’t be as strict
as they are in the UK. I think overall
in Europe, you’ll find that there are
more patients that will end up, because
of these guidelines, going straight to
an anti-TNF therapy when they have active disease. INTERVIEWER: Philip, what
has your experience been in the USA? PHILIP: I agree with Dafna that
there are many clinicians that are wanting to proceed with
use of a biologic medication first, before methotrexate. But insurance companies
have historically made us step through use
of methotrexate first. At least at this
juncture, even if they do have that requirement
still in place– and it may take a while
for these guidelines to really penetrate
into the payer arena– I think that this will give some
ammunition to rheumatologists who want to push back
and request that they be able to use a TNF inhibitor,
either first line or at least earlier in the
treatment paradigm. INTERVIEWER: Are
there any limitations of the new guidelines? OLIVER: I guess one
of the questions I had was the definition
of active disease and the threshold across which
patients have to cross in order to be considered for treatment
with an anti-TNF therapy. And one of the concerns would
be that you might have patients with relatively low
level of disease– perhaps with just
one or two joints– who might end up being treated
with an anti-TNF therapy because of these guidelines,
when they might equally be treated, for example, with– an intra-articular injection
for many of these patients may be sufficient, at
least for a period of time. DAFNA: So Oliver, with
regards to the definition of active PsA– it was defined
as “an unacceptably bothersome level as reported by
the patient and judged by the examining
health care provider to be due to PsA based on
the presence of at least one of the following: Actively
inflamed joints, dactylitis, enthesitis, axial disease,
active skin and/or nail involvement, and/or
extra-articular manifestations, such as uveitis or
inflammatory bowel disease.” So… OLIVER: Yes. DAFNA: I think it’s clear that
you’re not going to just get anybody moving on here. This has to be a significant
disease for the patient. It also says that the
health care provider may, in deciding if the
symptoms are due to active PsA, consider information
beyond the core information from the history and physical,
such as inflammatory markers– CRP or ESR– and imaging. OLIVER: I just
wondered whether people feel that the fact that a
lot of the recommendations are based on the very
low levels of evidence, whether that might
also be a limitation of these new guidelines– of any of the
guidelines, I guess. PHILIP: That’s certainly
a good point, Oliver. It’s commented
over and over again that the recommendations
are conditional, which means that they were
indirect comparisons as opposed to based on data from
head-to-head trials. DAFNA: Well, one
other limitation is the fact that by the time
these guidelines come out, including the ACR/NPF
guideline, there are already other
investigations on the way. So for example, the SEAM
study was in process at the time of the
guideline development, but it wasn’t out yet
and so it couldn’t be included in the GRADE
analysis of the literature. Both the European guidelines and
the GRAPPA guidelines are now almost three years ol–
three, four years old– and a lot of the drugs
that were included in the ACR-NPF
guideline not included in the earlier guidelines. DAFNA: All the guidelines are
currently undergoing revision, and so the new
pieces of information will come into play, but that’s
a limitation of the guideline, is because it takes anywhere
from one to two years to work through recommendations
by the time they come out, and they come out several
months after the completion of the work. Then there’s new information,
because life goes on and further research evolves
during that period of time. INTERVIEWER: Philip, what
other key research in this area has there been since the
publication of the guidelines? PHILIP: Now the SEAM study that
Dafna referred to is published, and I think that’s a
very interesting trial. There were over
850 patients that were enrolled and randomized to
receiving either methotrexate alone, etanercept alone, or
the combination of the two. And what was striking
about the study was that the median disease
duration was six months, which means that these were
patients very early in their treatment course. PHILIP: We saw
that etanercept was more effective than
methotrexate in achieving the primary endpoint
of ACR20 response, and, interestingly, the
combination of etanercept and methotrexate did
not yield any more value in achieving that response
than etanercept monotherapy. So in that primary outcome,
it did support the ACR/NPF guideline outcome. PHILIP: But the other
side of that coin was that I think everyone
was taking in the fact that methotrexate
was pretty darn effective in several areas. Nearly 50% of patients
achieved an ACR20 response. There was effectiveness in key
domains such as enthesitis, dactylitis, and skin disease. PHILIP: A limitation
of the study was that it didn’t
have a placebo arm, so it makes it a bit
hard for us to tell the true impact of methotrexate
compared to placebo, but I think it gives us some
reassurance that methotrexate can be effective,
and in some parts– especially in parts of the world
that are resource challenged, methotrexate still remains
an important medication that’s affordable to be
used for the treatment of psoriatic arthritis. INTERVIEWER: Finally, what
future research developments are ongoing, and how
can we expect these to impact on clinical practice? PHILIP: I’m very aware
of the head-to-head study between an IL-17 inhibitor
and a TNF-inhibitor. And we’re gaining appreciation
that the IL-17 inhibitor can be as effective in certain
domains, if not more effective in certain domains,
such as the skin domain, and the safety
profile of the IL-17s is proving to be
overall very good. So I think that that’s
an example where new head-to-head
research is going to help shape the guidelines. DAFNA: So there are a
number of key research areas that need to continue. One of them is additional
head-to-head studies, understanding the
drugs that we’re using currently a little bit better. And I think the
most important one will be work to define what
would be the most relevant drug for an individual patient. In other words, either
a personalized approach or a precision medicine
approach that would actually give us the true answer
for an individual patient. And that, we’re
still waiting for. You probably wouldn’t
need any guideline if you had that information. PHILIP: Agree completely. The world of oncology cancer
treatment, for example, is way ahead of us in
terms of being guided by either genetic or
other types of biomarker profiling of patients to guide
the clinician in choosing the most precise and
effective treatment. And I am sure that
eventually we’ll get there in rheumatology,
but we’re not quite there yet. And that certainly is a goal
and a research aim for a number of different groups. OLIVER: Yeah, I think
give it five years and we’ll have a lot more
data in that particular area. INTERVIEWER: So
while application of some of the
treatment guidelines may be limited by prescribing
regulations outside the USA, they nevertheless provide
impetus for rheumatologists to use TNF inhibitors
earlier in the treatment of psoriatic arthritis, while
the SEAM study, published after the guidelines,
provides reassurance that methotrexate as a
first-line treatment is not a futile choice. These guidelines, together
with future head-to-head trials and studies on personalized
medicine to manage the disease, brings hope to the treatment
landscape for this condition. INTERVIEWER: Thank you very much
to Dafna, Philip, and Oliver for sharing their thoughts
with us on this topic. You can find links
to the other podcasts in this series on Medicine
Matters Rheumatology. [MUSIC PLAYING]

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