Understanding the Comorbidities: Psoriasis and Metabolic Syndrome - Episode 9

Decreased Efficacy, PASI Score vs BSA, and Nonresponders

The panel discusses the potential for decreased efficacy of treatment based on comorbidities. They also discuss the use of PASI score vs BSA to determine severity of disease and the need to identify responders and nonresponders to specific agents.


Peter L. Salgo, MD: Let’s examine a little more, this interrelationship because Th-1 [type 1 helper cell], Th-17 mediators are primary mediators in metabolic syndrome. Does that fact make it more difficult to treat psoriasis in patients with metabolic syndrome than it would be in patients with psoriasis without metabolic syndrome?

Joel Gelfand, MD, MSCE, FAAD: Well first of all, I think that most of the data really link Th-1 pathways to metabolic syndrome. The data for IL-23 [interleukin-23], IL-17 pathways are really more emerging at this point and somewhat controversial. But I think, as we mentioned before, the obesity component of it was what makes it challenging. When people are more overweight, they tend not to respond as well to therapies we use. They tend to lose response more frequently.

Peter L. Salgo, MD: There’s a study, right, the PSO-BIO-REAL study. What is that? What does that show? Does anyone have data on that? Why are you laughing?

Peter Dehnel, MD: There are a number of studies out there. If either of these gentlemen knew the specific reference, I would be fascinated to hear it.

Steven Feldman, MD, PhD: In that study, they found that rates of psoriasis treatment failure were higher in the patients with more comorbidities.

Peter L. Salgo, MD: That’s what I was getting at.

Steven Feldman, MD, PhD: Yes. And it could relate to the immune mechanisms. I can’t say that it doesn’t. I’m very interested in how poorly patients take their medicine. It could be that people with comorbidities have other things going on, and for some reason they may not be as good at taking their psoriasis treatments.

Peter Dehnel, MD: Cure management is 1 answer that may be for some of this, especially for people with complex care. It may be a matter that some of these other comorbidities that they’re taking treatment for interfere with the treatment for the psoriasis.

Steven Feldman, MD, PhD: Yes, it could be beta-blockers for their hypertension. It could make psoriasis worse.

Peter L. Salgo, MD: What about the PASI [Psoriasis Area and Severity Index] score, is anybody using that?

Joel Gelfand, MD, MSCE, FAAD: In clinical trials for research we do that. In clinical practice, not so much. It’s not particularly helpful for clinicians to do it. It’s time-consuming and burdensome. Typically in clinical practice, at least from the AAD [American Academy of Dermatology] point of view, we recommend providers do maybe a body surface area assessment. Maybe a global assessment. You know, a simple 0 to 5 scale, if you will, to give a general idea of how thick and scaly the plaques are.

Steven Feldman, MD, PhD: One of the nice things about insurers is that, to get into a psoriasis study, you have to have a PASI score of 12 or higher. And so you might think that an insurer would say, “Well, before we’re going to give you these drugs that are approved by the FDA, you should have a PASI score of 12 or higher.” But almost no dermatologists do PASI scores in the clinic. And as far as I’m aware, given that that’s the standard of care, no insurer, or very few, would ever ask a dermatologist, “Well what was the PASI score?”

Joel Gelfand, MD, MSCE, FAAD: Oh, I’ve seen that. It’s so variable, that’s the issue.

Steven Feldman, MD, PhD: But it’s not that common. By and large the standard of care is the body surface area.

Joel Gelfand, MD, MSCE, FAAD: Oh, absolutely. But I think there are so many payers in the country, and where you are regionally. I’ve had some request PASIs and deny coverage because there was no PASI in the chart.

Peter Dehnel, MD: To both of these points, I think that what we require is a definition of moderate to severe disease.

Joel Gelfand, MD, MSCE, FAAD: Yes.

Peter Dehnel, MD: And then you’ll be more eligible for other products, as opposed to someone who just has mild disease. And you may not want to treat people with mild disease with more aggressive treatment because of the complications of that treatment.

Peter L. Salgo, MD: If you’re going to have the same kind of risk profile, then the trick would be to identify those people who would benefit from these drugs. Is there a way to stratify patients into responders and nonresponders?

Steven Feldman, MD, PhD: We used to really feel the need to have a test to know who the responders are and who the nonresponders are. The IL-17 and IL-23 drugs, pretty much everybody is a responder. The number of nonresponders is so small that I’m not sure I would want to have a test to try to detect them.

Peter Dehnel, MD: In your experience, with some of the biologics, they will want to do testing for antibodies to these medications. Is there any sense of needing an antibody profile against these newer agents that are IL-17s?

Joel Gelfand, MD, MSCE, FAAD: Well, the newer therapies are associated with very low rates of drug-related antibodies, and it’s not clear that they are clinically important in that. The first biologic to market was infliximab, right? And in that drug very common rates of antibody formation to it as well is clinically important because they would lose response, need higher drug levels, or they would have more rates of anaphylaxis. With the subcutaneous administered drugs, it’s not as much of a clinical problem.

Steven Feldman, MD, PhD: I think the gastroenterologists rely on these drugs. And I’m not sure what they would tell us because if a patient is failing the drug, if the antibody tested positive, you have to stop the drug. If the antibody tested negative, you’re going to move on to another drug anyway. So I’m not sure what the value is.

Joel Gelfand, MD, MSCE, FAAD: I think that it came out of the fact that they had 1 mechanism of action for many, many years, right? And so they had to do whatever they could to figure out if is this TNF [tumor necrosis factor] is going to work for this patient long term. And we’ll see. They may even get less interested in that type of test now that they have more mechanisms that are effective for disease.