WYNNIS L. TOM, MD: And I m Dr. Wynnis Tom. I m Associate Professor of Dermatology and Pediatrics at the University of California, San Diego.

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1 LEARNING OBJECTIVES At the conclusion of this activity, participants should be better able to: Assess the severity of atopic dermatitis (AD) and its impact on the patient Evaluate treatment efficacy Design strategies for proactive management of AD LAWRENCE F. EICHENFIELD, MD: Welcome to our program. I m Dr. Larry Eichenfield, Chief of Pediatric Dermatology at Rady Children s Hospital and Professor of Dermatology and Pediatrics at University of California, San Diego. We have a set of video modules discussing atopic dermatitis and I have excellent co-faculty with me. JONATHAN I. SILVERBERG, MD, PHD, MPH: I m Dr. Jonathan Silverberg, Assistant Professor of Dermatology, Preventive Medicine and Medical Social Sciences at Northwestern University Feinberg School of Medicine. WYNNIS L. TOM, MD: And I m Dr. Wynnis Tom. I m Associate Professor of Dermatology and Pediatrics at the University of California, San Diego. DR EICHENFIELD: This module is about optimizing therapy in atopic dermatitis. My first question: What s the best way to assess atopic dermatitis severity and the response to therapy? DR TOM: This is an interesting question. I think in clinical trials it s pretty clear we have very good standardized severity scores, including the Eczema Area and Severity Index (EADI) and Scoring Atopic Dermatitis (SCORAD). We also have patient assessments where patients get to include their outcomes as part of the evaluation. But once you move into the clinics, it becomes less clear, because these are pretty 1

2 cumbersome, time-consuming measures, not easy to utilize in a very busy clinical practice. Would you agree, Dr. Silverberg? DR SILVERBERG: Absolutely. Many of the trial outcomes, like EASI and SCORAD, are now the preferred outcomes for clinical trials identified by the Harmonizing Outcome Measures for Eczema (HOME) group, the international consensus group. But they all require extensive training. There are also some major challenges with respect to inter- and intra-rater reliability. These issues limit the potential for using these in clinical practice. DR EICHENFIELD: As practitioners we should know about them, because when the studies come out that s how we figure out what the results mean. But in clinical practice, then, how do you approach your clinical assessment? How do you look at severity and how do you use that to determine treatment? DR SILVERBERG: I think there are some lessons to be learned from these measures, like EASI and SCORAD. They fit conceptually with what we do in clinical practice, which is that they factor in both the severity of the actual lesions that patients have, as well as the extent of the lesions. And they take into account the symptoms as well. Some patients may have very localized disease, while others may have very extensive disease, whether that involves very thick lesions or very thin lesions. And then some patients may have less extensive disease, but it s really severe, intense, and refractory, and that might bump them up and make us recognize that they have moderate to severe disease. Location, which you were just alluding to, is another important factor, because there are certain areas that are more functionally significant than others for example, the hands and the feet. When patients can t walk, even if their disease is considered to be localized, it can be so debilitating to them that you need to step up therapy. Quality of life is another huge concern. We know that this is a highly symptomatic disease and something that can significantly reduce all aspects of patients quality of life. DR EICHENFIELD: Wynnis, what do you ask to get a sense of how the disease is affecting the individual? DR TOM: There are several key questions: How often are they having lesions? Is this a continuous process? Has treatment reduced symptoms but the problem keeps coming back? Or have treatments not worked? And exactly what types of treatments? Certainly you ll have a lot of patients who have had minimal treatment or who are using very lowpotency topical steroids. And then you have some who maybe have been managed more aggressively, or who are later on in the course of their disease, and that s a gauge that indicates the refractoriness of the disease. I also ask about quality of life. Sleep is a major issue. Even when we 2

3 think the skin looks better, if there s significant itch and they re still not sleeping, that can have a huge impact on their quality of life. DR EICHENFIELD: We have the responsibility to figure out which patients need which treatment, especially given the new systemic and topical therapies, compared to traditional medicines. The questions you pose are at the core of what we do. Such questions are going to be increasingly important. We have to document that patients are failing and document the impact on the individual. We need to convey the message that our patients shouldn t be walking around with a lot of eczema, with a lot of disease impact, with a lot of sleep disturbance or other comorbidities. DR SILVERBERG: A not-uncommon scenario I encounter is one where patients come in and they look pretty mild on that day of the visit. You make the judgment that this is a mild patient, someone I can manage with mild topicals. And they ll say, Yeah, but Doc, 2 weeks ago I had the most severe flare of my life and needed to go to the emergency room. We must recognize that sometimes what we re able to see may just not be an off time. You have to really take into account the global history of disease. DR EICHENFIELD: One thing I do to is to assess the patient s use of medicines and the quantity of medicine they re using. Some patients say they re using the medicine twice a day and then say they ve used 15 grams over 4 months. That tells me they re not using it twice a day. Knowing the quantity of medicine that someone is using gives us a helpful sense of how active their disease is. More importantly, it reflects how much active therapy they re doing. We don t have time to talk about all the basics of skincare and bathing and moisturizing. Let s presume people are doing that, but they come in and they have active disease. How do you line up your first-, second-, and third-line agents? DR SILVERBERG: Again, for patients of all severity, we re going to reinforce the importance of avoiding triggers and of using all those basic skincare approaches that are the prerequisites for care. But our starting point generally would be to use topical steroids or topical calcineurin inhibitors. The potencies used will vary based on the location of the disease on the body, and certainly age will factor into our choice as well. But if a patient is compliant and has done an adequate course of topical therapy without achieving good control of the disease, then we have to think about stepping up to stronger options, such as phototherapy or systemic treatment. It can be tough decision to step up therapy. 3

4 DR EICHENFIELD: Stepping up might mean increasing the strength of a medication or switching to a systemic agent. Sometimes it means stepping up to a combination approach with different types of agents, whether that involves topical steroids, the calcineurin inhibitors, or the newest type of agent, crisaborole, a topical PDE-4 inhibitor. We have options for how we build up our treatment regimens. But when dealing with a child who has more persistent disease, how do you decide when to go beyond topical corticosteroids? DR TOM: One key factor is the extent and refractoriness in the sites. Certainly there are sensitive skin areas, like the face, private areas, and flexures, where we d be more worried about long-term side effects. That s where you re going to use nonsteroid therapies. Concerning the quantity of medicine, as you said, a lot of times patients underuse their medication, but once in a while they overuse. If they re putting on potent corticosteroids all over the body every day in order to maintain control, we worry about absorption and long-term risk. I also factor in concerns about quality of life. This disease impacts the entire family. It can affect school or work performance and can lead to lost days of attendance or lower productivity. And those factors need to be taken into account considering stepping up therapy. DR EICHENFIELD: How do you handle proactive or preventive management? DR TOM: I think that s important for every patient. The first thing of course is to get the acute flare under control. But we know this disease is going to be chronic for quite some time, and the likelihood of a flare coming back is pretty high. For most patients I recommend that they slowly taper, but not completely stop, the treatment. I will offer a scheduled proactive maintenance plan where they re treating with topical steroids or topical calcineurin inhibitors 2 to 3 times a week on a scheduled basis. Treatment usually focuses on areas that tend to be recurrent, not all over the body. We usually find that patients achieve better control and have fewer flares and need to use less medication if they take this proactive approach, rather than stopping therapy and waiting several weeks to see how well they do using nothing but emollients. Often in such cases patients have a big flare again, and then you have to use much higher quantities. DR EICHENFIELD: We ll discuss the newer topical agent, the PDE-4 inhibitor crisaborole, in another module in more detail. This agent wasn t studied in a proactive regimen. But do you think it might have 4

5 a role in proactive regimens? DR SILVERBERG: Probably. We certainly see that the topical calcineurin inhibitors, in addition to the topical steroids, have demonstrated efficacy in that sense. So I think that it s reasonable. DR EICHENFIELD: They weren t studied in a proactive manner, but in the long-term safety study crisaborole was used in this interesting method. Patients were seen every month. If they had active disease that was other than almost clear or clear, they applied the therapy BID for the month and then came back. There were a lot of patients who used their drugs fairly regularly and had good disease control. Keep in mind this was predominantly a safety study. It will be interesting to see how that works over time. DR SILVERBERG: I think this gets back to the question asked earlier about assessing patients. Those questions asked at baseline, such as how many flares do you have, can establish up front whether this is the kind of patient who has 1 flare a year during wintertime, or the patient who has flares 365 days a year, or who has so many flares throughout the year they need a long-term proactive approach. You can often know quite early on what you re up against. If the patient has episodic disease, maybe a proactive approach with medications is not as necessary; maybe what s needed is proactive moisturizing and the use of nonpharmacologic approaches. But if you find out the disease is chronic, you re going to have to treat it that way. DR EICHENFIELD: When, if ever, do we stop therapy? DR SILVERBERG: That s a great question. The thinking is much the same: If this is a patient who you think will have a great response to topical steroid, but if they stop treatment and the disease is just going to come right back again, why would you stop it? You have to at least have some kind of maintenance approach on board for the long term. DR EICHENFIELD: When I talk to families, as well as other doctors, I often refer to the parallels with the model for treating asthma. A lot of families get that, especially in pediatrics. I say, Look, we re going to come up with a regimen that will get your disease in good shape. If you re doing well, perhaps over time you won t need to use moisturizers every day; you might need them only now and then. But right now that s not the issue. You want to get the acute disease under control, and then you get the chronic disease under control so you re chronically not manifesting the disease, and then down the line we can talk about stopping therapy. Of course, it s possible that our newer therapies might change the course of the disease. We ll see about that in the future. Thank you very much for joining us for this module. And thanks to this great faculty. Faculty Disclosures Lawrence F. Eichenfield, MD: Consultant: Novan, Inc.; Steifel, a GSK Company*; Valeant Pharmaceuticals. Investigator: 5

6 Cassiopea; Galderma Laboratories, LP; Novan, Inc.; Steifel, a GSK Company; Valeant Pharmaceuticals. Jonathan I. Silverberg, MD, PhD, MPH: Consultant: AbbVie Inc.; Anacor Pharmaceuticals, Inc.; Galderma Laboratories; GlaxoSmithKline; Lilly; Medimmune-AstraZeneca; Pfizer Inc; Proctor & Gambel; PuriCore PLC; Regeneron-Sanofi. Investigator: AbbVie Inc.; Celgene Corporation; Chugai Pharma USA, Inc.; GlaxoSmithKline; Lilly; PuriCore PLC; F. Hoffman- La Roche Ltd.; Regeneron-Sanofi. Advisory board member: Anacor Pharmaceuticals, Inc. Speakers bureau: Regeneron- Sanofi. Wynnis L. Tom, MD: Investigator: Anacor Pharmaceuticals, Inc.*; Celgene Corporation; Janssen Global Services, LLC; Medimetriks Pharmaceuticals, Inc.; Otsuka America Pharmaceutical; Inc.; Promius Pharma; Regeneron-Sanofi. Advisory Board member: Anacor Pharmaceuticals, Inc. (*past) This transcript has been edited for clarity and consistency. 6