Measuring Outcomes in Atopic Dermatitis

Peter L. Salgo, MD: It’s that old super hero model. You knew the job was dangerous when you took it. Jonathan, what are the advantages, as you see it as a clinician, of these new emerging therapies?

Jonathan Silverberg, MD, PhD, MPH: The key thing for almost all of these new emerging treatments is really safety. It’s that balance between the safety and the efficacy. We have on the topical side, topical steroids, which technically are effective, but we’re limited in how long we can use them, and that ultimately leads to poor real world effectiveness. When you think about systemic agents out there, our options are systemic steroids, cephalosporins, methotrexate, and azathioprine. These are scary drugs.

Peter L. Salgo, MD: I was going to say, as an internist sitting here listening to those names, I’m beginning to shake, and I’m not paying for them.

Cheryl Allen, BS Pharm, MBA: And none of those drugs are approved.

Jonathan Silverberg, MD, PhD, MPH: Exactly. None of them are approved.

Peter L. Salgo, MD: They’re all off-label, are they?

Jonathan Silverberg, MD, PhD, MPH: Exactly, all off-label, and they come with some hefty baggage. So, the issue is for patients who do get treated with these drugs, they get a lot of iatrogenic complications because of them. And for many of the patients, they’re just not being treated with them at all. They’re just miserable because there’s this fear and reluctance to using them.

Peter L. Salgo, MD: Okay. Let’s come back now to these two new drugs that are creeping up, that are on the horizon. What are their advantages in your opinion?

Jonathan Silverberg, MD, PhD, MPH: So, crisaborole, on the topical side, is a nonsteroidal agent that, at least based on the data that we’ve seen so far, looks like it has some pretty good efficacy. It may rival something equivalent of a mid-potency topical steroid, but has that advantage that you could use it longer term in patients without worrying about those safety issues. On the flip side, when you think about dupilumab, for starters, the efficacy is really the best we’ve ever seen so far. It may be, with this drug, we get better results than with anything that we even have right now. But, on top of that, it’s the ability to keep patients on at longer term. The current standard right now with, let’s say, steroids would be [to] give them a 5-day course of steroids. They may do well while they’re on it, but then they rebound or they get this severe flare down the road. And so, for patients who are chronic, who have persistent disease, we have at least the safety behind it and the efficacy data to suggest we could keep them on it longer term.

Cheryl Allen, BS Pharm, MBA: I have a question, though, back to the SOLO studies. Investigators Global Assessment (IGA), is that something that you use in your practice?

Jonathan Silverberg, MD, PhD, MPH: No. And, in fact, the Investigator Global Assessment is very challenging. There’s actually a fascinating systematic review that just published this, I think, the past couple of months that shows there’s about 47 different Investigator Global Assessments out there, and they’re not all the same. This is a global measure that the FDA likes. It’s not one that really has any validity behind it. Our preferred assessments, I think we’ll talk about that a little later, are ones that also are not really used clinically, but are ones that at least have a little bit more methodologic validity around them, like the EASI score or the Scoring Atopic Dermatitis, the SCORAD. So, using this IGA is a little tricky from a clinical standpoint, and there’s going to be a little bit of a disconnect between the trial outcomes versus what we would probably use in the real world.

Peter L. Salgo, MD: I think I know the answer to this, because we’ve been talking about, but are the payers really paying attention? I know you are, but are all payers as attuned to it as you are or is this going to come as a big surprise very soon? And what about the specialty pharmacies? Because they’re going to be the pharmacies providing these drugs. Are they aware?

Jeffrey D. Dunn, PharmD, MBA: Payers will be aware of this as far as the pipeline, for sure.

Peter L. Salgo, MD: What about the specialty pharmacies, what do you think?

Cheryl Allen, BS Pharm, MBA: Absolutely.

Peter Salgo, MD: Are they aware now? If I were to call a specialty pharmacy about these new drugs, what would they tell me?

Cheryl Allen, BS Pharm, MBA: Yes, they will. National Association of Specialty Pharmacy will meet next week in Washington, and in the pipeline presentation, there’s actually a segment on atopic dermatitis. We’ll walk through these drugs that are in phase III now, and there are actually drugs that are in phase II. So, payers are aware of that. They’re looking at cost. Specialty pharmacies are monitoring this for our patients and for education purposes.

Jeffrey D. Dunn, PharmD, MBA: What Jonathan said, I think to me personally, is one of the top three or four issues right now with this. We don’t have objective measures. So, if they’re not using IGA or EASI, it’s hard for us to have a beneficial discussion with a physician or provider about is this drug working and when to start it and when to stop it when all we’re getting back is the patient feels better.

Peter L. Salgo, MD: Well, if the patient feels better, what’s wrong with that? But, again, what you’re looking for is a metric, right?

Jeffrey D. Dunn, PharmD, MBA: And if it’s free, fantastic. There’s a dollar associated with that. That’s why I have to have that conversation.

Jonathan Silverberg, MD, PhD, MPH: The issue with the, let’s say, for example, dupilumab—which I think is going to be the more costly or the systemic agents in general will be the more costly ones—is these are not meant to replace a topical steroid or any topical agent for that matter. They’re really designed for those patients who are refractory or somehow contraindicated to the topical agents out there. That’s going to be a much tinier segment of the population, but those are also the ones who they’ve already expended, they’ve already gone through all the generic cheap stuff that you’re comfortable with and there’s nothing left.

Jeffrey D. Dunn, PharmD, MBA: I don’t disagree. I think, at some point, we will get there where the initial utilization management will be step therapy. You’ve tried these other agents or you have a contraindication. That’s just to be expected, and that may be loosened up over time as we get more comfortable.

Peter L. Salgo, MD: Other disease stages have gone that route, right?

Jeffrey D. Dunn, PharmD, MBA: Exactly.

Peter L. Salgo, MD: Step, step, step and then, wait a minute, we don’t need to step anymore.

Jeffrey D. Dunn, PharmD, MBA: And, to your point, if a drug is not working, you would think because of the cost and the member out-of-pocket and everything else that these patients would stop taking the drug. But, again, we still want, from a payer perspective in an ideal world, to have some consensus around when do you start, when do you stop, who’s the appropriate patient, what is the objective measure for us, if this drug is working.

Peter L. Salgo, MD: I’ve been listening to you and something that crossed my mind as an internist, not as a dermatologist, is you’re going to wait for a flare, then use these drugs. But if this is a chronic disease and it’s always there, whether it’s simmering along or just bursting out, wouldn’t it be better to suppress? And if these drugs are useful long term, why not just keep somebody on it?

Jonathan Silverberg, MD, PhD, MPH: We try that in dermatology all the time, in general, working on everything we can prevention-wise that wouldn’t require pharmacology—moisturize or avoiding triggers, things like that. So, we’re doing the best we can with this already, but sometimes even with the best practices, you can’t fully avoid these flares. There is definitely a big shift in the field to try to work on prevention of flares, and we do that now even using some of the topical steroids, where you could use it a couple of times a week on clear skin to prevent flare-ups from happening. But it’s sometimes just not enough, and you fall right back into that trap where patients are using topical steroids every day and are going to run into the side effect issues. When it comes to the systemic therapies, it’s very hard to use anything we have right now for prevention of flare-ups because that would require keeping them on it for extended periods of time.

Peter L. Salgo, MD: Ever.

Jonathan Silverberg, MD, PhD, MPH: Exactly. And then there’s the safety issue that just comes up almost immediately.