Clinical relevance of complete skin clearance in psoriasis

Clinical relevance of complete skin clearance in psoriasis


Good day, my name is Bruce Strober. I’m Professor and Chair of Dermatology at
the University of Connecticut Health Center. Today I’ll be discussing a paper regarding
clinical meaningfulness of complete skin clearance in patients with moderate to severe psoriasis. This concept was discussed extensively in
a paper recently published in the July issue of the Journal of the American Academy of
Dermatology, the blue journal. In essence, this paper examines patients in
clinical trials for the IL-17 receptor blocker brodalumab and whether it made clinical difference
if they achieved PASI 75, PASI 90, or full clearance: PASI 100, or sometimes PGA 0 (anyone
who’s a PGA 0 should be a PASI 100, by the way). In the past, the FDA and other regulatory
bodies have mandated that drugs purporting to treat moderate to severe psoriasis be first
and foremost measured as high achievements of PASI 75 or Physician’s Global Assessment
(PGA) 0 or 1. You don’t have to be 0 (0 or 1). Basically, the FDA is saying if you achieve
a PASI 75 or PGA 0 or 1 as a patient with moderate to severe psoriasis, you are a success
story. And we’ve always wondered, well, PASI 75
is good, is PASI 79 better? And is PASI 100 better than PASI 90 to PASI
99? And now I think we’re better able to answer
that question because of this particular analysis. Now, how do we measure whether PASI 100 is
better than PASI 75 or whether PGA 0 is better than PGA 1? We do it because we have metrics of quality
of life that we can concomitantly utilize in a clinical trial setting and we also have
metrics of symptoms specifically geared towards patients with moderate to severe psoriasis. So, our tool to measure quality of life in
this study was called the Dermatology Life Quality Index, the DLQI. And the DLQI is simple: it’s 10 questions,
scored 0–3, based on symptoms and psychosocial aspects of having skin disease, not psoriasis
specifically. That’s an important point—the DLQI was established
about 25 years ago as a metric for a variety of skin diseases, not just psoriasis, so including
acne and atopic dermatitis. But the DLQI still has validity in psoriasis
and is really a gold standard quality of life instrument. The other tool we use is called the Psoriasis
Symptom Inventory (PSI). That’s new, and Amgen developed this basically
at the behest of the FDA to measure specifically symptoms that are really aligned with the
patients who have psoriasis and their experience. So the Psoriasis Symptom Inventory, in short,
is an eight-item quick questionnaire conducted by the patient, measuring symptoms such as
flaking, scaling, burning, stinging, itch, pain, bleeding, redness—all of those are
measured in this instrument, and the patient basically scores them on a scale. And to be a success in this PSI, you could
either be a total 0 (and that’s called PSI 0)—basically you have no symptoms—or you
could be a composite score of 8 or below; there’s two different ways to define success. Obviously, 8 or below is not as good as total
0, so we looked at both. And finally, another aspect of quality of
life that was measured in these studies was the number of days during the study the patient
was 100% free of symptoms, alright. That’s a good measure—days where people
with psoriasis forgot they had psoriasis because they weren’t reminded they had psoriasis. And so that was another good way to measure
how quality of life was going for patients. And again, we always will correlate regarding
objective assessor response— PASI 100, PASI 75, PGA 0 or 1. Here’s the nutshell: a greater percentage
of patients showing PASI 100 fully cleared, were PSI responders of 0 total, were DLQI
responders of 0 or 1, were more likely to have many more 100% symptom-free days when
compared to people who were PASI 90–99. So, you would think a person PASI 90–99
would be just as good as a person who has a PASI 100, but you would be wrong. On average, there’s a difference, and clearly
PASI 100 patients do better than PASI 75 patients. So, the findings here from this study demonstrate
clearly that PASI 100 is a relevant clinical endpoint in that it discriminates between
people who are really happy symptom-wise and quality of life wise and only somewhat happy. People who are PASI 100 are more often doing
well symptoms-wise and quality of life wise and, of course, that’s intuitively correct. There should be no doubt that 100% clearance
more often leads to happier patients on all aspects of their quality of life, but it should
be emphasized that, in my opinion, this shouldn’t be the ultimate treatment goal. In other words, you’re not failing the patient
if you don’t get them to PASI 100; we all know that certain patients are happy at PASI
75 but not PASI 90, certain patients are actually happy at PASI 60, PASI 50—it will be still
patient-specific. When we do these studies, we’re looking
at populations and, on average, we can make comments about PASI 100 being better than
PASI 75. And also there are other issues that surround
the concept of complete clearance. One: if clearance, complete clearance, comes
at a price that really offsets the benefit then it’s not a good idea. So, for example, if complete clearance means
less safety then we have a problem. Now, the one good news about the new biologics—the
IL-17 inhibitors and some follow-on drugs that are coming down the line—is they actually
clear people with really great tolerability and very little or unable-to-measure safety
problems. So reality has it that the new biologics,
being so specific in hitting the right targets, might be just as safe as the older biologics—might
be safer, it’s left to be seen— yet clear patients better. That’s a sea change advance in our therapy. The newer biologics, though, might be costlier,
they might be less tolerable, they might require more follow-up visits—it’s left to be
seen there. I’m not seeing that, but obviously if that
were the case, clearance comes at too great a cost and we might want to revert back to
the older drugs, which are easier. I, again, will close by saying the issues
will not likely be convenience, will not likely be dosing regimens or tolerability, they all
look good for the new biologics. It’s going to come down to cost and access
and, reality has it, it’s going to come down to comfort of patients and their treatment
practitioners with new drugs. My analogy is this: of course PASI 100, and
PASI 90 for that matter, will become new standards; it’s inevitable, over the next decade. Much like we all have better smartphones than
we did 10 years ago (and we would never go back to our smartphone from 10 years ago),
or we have better cars than we had 10 years ago—even though the cars of 10 years ago
were fine, the cars now are better. They have more features: they have GPS, they
have cameras that allow you to back up more comfortably, they have lane-change sensors to tell you when you’re about to sideswipe somebody. All these are features we are now going to
take for granted and will never want to lose in cars going forward. The same with biologic therapy for psoriasis:
the old drugs were very good, the new drugs are great and don’t appear to be coming at
a cost. And, from that point of view, I think we need
to accept that higher levels of clearance will be acceptable and, really, in most cases
demanded by both practitioners and their patients.

Leave a Reply

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