Ixekizumab for the treatment of psoriasis

Ixekizumab for the treatment of psoriasis


Hello, my name is Kenneth Gordon. I’m a dermatologist at Northwestern University,
and I’ll be discussing a recent New England Journal of Medicine article on the medication
ixekizumab for the treatment of psoriasis. This article is a compilation of three Phase
3 trials looking at the short-term data from one trial and longer-term data from all three
put together. It’s important to put ixekizumab in the
context of all the new medications we’ve developed for psoriasis over the last 10 to
15 years. We’ve had numerous biologic medicines develop,
starting in 2003, that we’ve had access to. But what’s really different and what’s
gone on over the last few years is the development of new levels of efficacy that we can use
for treating our patients with psoriasis. The standard we’ve used for many, many years
has been the PASI 75, where 75% improvement in the Psoriasis Area and Severity Index. When we first started with medications like
alefacept and efalizumab, we had levels of response of about 25–30%. That was improved upon with the anti-TNF agents:
etanercept, of about 50%, and adalimumab, of about 75%; and ustekinumab was in the same
context as adalimumab, about 70–75% PASI 75. But with the advent of the newer medications
blocking interleukin 17, like secukinumab but in this case ixekizumab, what we found
is higher levels of response. Numerous areas of information have suggested
that getting higher levels of response, at least a PASI 90 (or 90% improvement in the
PASI) or even a PASI 100 and complete clearance, really makes a difference to our patients. We were really never measuring those numbers
before because the numbers of subjects in clinical trials that reach those levels was
relatively low. However, studies like those that were published
in this article really suggest that those levels are attainable. So, let’s go through the article for a moment. The important thing is looking at the short-term
and long-term data associated with ixekizumab. We have one of the short-term trials, 12 weeks
of ixekizumab versus placebo in this trial, and it showed a PASI 75 rate in the high 80s
and approaching 90%, PASI 90 about 70%, and PASI 100 (complete clearance) approaching
35–40% and that was consistent with the data that was seen in other short-term trials
with ixekizumab. But even more important was looking at the
longer-term data where the PASI 75, PASI 90, and even complete clearance was maintained
very nicely over 60 weeks of therapy. This is the kind of response that we haven’t
seen before in psoriasis therapy and really adds to our ability to take care of patients. I think there’s one other piece of important
information in the efficacy portion of this paper that’s hidden in the supplemental
materials of the paper, and that is looking at the production of antidrug antibodies and
their impact on disease and therapy. So one of the things that we’ve always wondered
is, what is the true impact of development of antidrug antibodies? How does it really impact therapy? Because the only thing that’s really important
is whether the patient is getting better or not. What we can see in this trial is that while
number of patients that had antidrug antibodies against ixekizumab, relatively few actually
had a clinical impact. So it was clear that the titers of the antidrug
antibodies were very significant, but only about 1.7% of patients had any impact on their
outcomes. What that tells us is that in a drug that
acts so highly on patients in terms of making them better, the presence of antidrug antibodies
really only distracts a very, very small proportion of the response. Obviously when looking at long-term therapy
for psoriasis, safety is of great significance as well, and the power of having a paper that
has all three major clinical trials in the Phase 3 program together gives a great deal
of power when looking at safety, with over 1200 subjects being studied. What we find in this trial is that even though
there is a little increase, a slight increase in the number of candidal infections that
we can see (and that would be predictable by the nature of the drug), these were very
mild and no patients had to stop the therapy based on candidal infections. Other things that we’re concerned about—things
like major adverse cardiac events, serious infections—were very, very low rates and
comparable to what was seen in placebo, and even with the comparator of etanercept. So, in looking at this paper in a larger sense,
what we see is very high levels of response along with a good safety record, and something
that we strongly believe is that ixekizumab, based on these data, should be a major player
in the treatment of psoriasis over the next few years.

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