Updates on Atopic Dermatitis Treatment Options and the Role of Biologics (Recording)
This webinar was recorded on September 18, 2024
Biologics are typically prescribed for people living with persistent, moderate-to-severe atopic dermatitis who need more than topical treatments. Biologic medications can reduce inflammation and calm the immune system in people living with atopic dermatitis. In this webinar, learn about the role of biologics in treating atopic dermatitis and the approved biologics that may help patients with moderate-to-severe AD.
Speaker:
- Peck Ong, MD
Dr. Ong is an Associate Professor of Clinical Pediatrics at Children’s Hospital Los Angeles and University of Southern California. He is an allergist with a special interest in atopic dermatitis. He has published over a hundred papers in atopic dermatitis. His 2002 New England Journal of Medicine paper on antimicrobial peptides in atopic dermatitis remains as one of the most cited papers in atopic dermatitis. His recent interests in atopic dermatitis include infections, prevention and unmet needs in treatments.
This Advances webinar is in partnership with the American College of Allergy, Asthma & Immunology. ACAAI offers CMEs for physicians for this webinar. If you are a member of ACAAI, you can obtain CME through the member portal for Advances webinars.
All attendees will be offered a certificate of attendance. No other continuing education credit is provided.
CME is available through ACAAI for this webinar.
Sponsored by the American College of Allergy, Asthma and Immunology
Transcript: While this transcript is believed to be accurate, errors sometimes occur. It remains your responsibility to evaluate the accuracy and completeness of the information in this transcript. This transcript is not intended to substitute for professional medical advice.
Catherine: We are going to go ahead and get started. I am Catherine Blackwell. I want to welcome you to this afternoon’s webinar. We are in for a real treat today with Dr. Peck Ong. We have a few housekeeping items. All participants will be on mute for the webinar. We will record today’s webinar and posted on the website within a few days. You can find all of our webinars on our website. All you have to do is scroll down to the bottom of the page to find our recorded webinars and any upcoming webinars and choose the one you would like to see. This webinar will be an hour long. That includes time for questions. We will take those questions at the end of the webinar but you can put your questions in the Q&A at any time. The Q&A box is located at the bottom of the screen and we will have someone monitoring the chat if you have questions or you need some help. We will get to as many questions as we can before we conclude today’s webinar. This is a partnership with the American College of allergy, asthma and immunology. AACI offers attendance credits. You can create a free account and obtain CME or attendance credits. All attendees will be offered a certificate of attendance and no other credit is provided. A few days after the webinar you will receive an email was supplemental information and a link to download the certificate of attendance. We will also try to add the link to the certificate in the chat. Let’s get started. Today’s topic is updates on atopic dermatitis, treatment options and the role of Biologics. Biologics are typically prescribed for people who live with moderate to severe atopic dermatitis who need more than topical treatments. Biologic medications can reduce inflammation and calm the immune system with people living with atopic dermatitis. It is my pleasure to introduce our speaker, Dr. Peck Ong. Dr. Ong is an associate professor of pediatrics at Children’s Hospital Los Angeles and University of Southern California. He is an allergist with a special interest in atopic dermatitis. He has published over 100 papers on the topic and his 2002 paper on and — remains one of the most cited papers in atopic dermatitis. His recent interests in atopic dermatitis include infections, prevention and unmet needs in treatments. Dr. Ong, thank you for being here and I will turn it over to you now.
Dr. Ong: Thank you. Welcome, everybody. This webinar has had significant changes in the treatments for atopic dermatitis since 2017. Today we will talk about some of these updates. This is the mission of AAN. This is my current position. Below are my disclosures. Regarding today’s objective, we will talk about the basic management of AD, or atopic dermatitis, first. The basic treatments such as daily skin care and topical treatment remains a critical part of the management of AD for a majority of the patients. We will touch on the physiology of AD and summarize upcoming treatments and will discuss some unmet needs in Capitol Peak Strategies. — some unmet needs in AD. This is an example of AD engine infant. Generally they have rashes on their face. In the older children and adults , you may see more distribution of the rash. The natural history of AD, majority of patients have onset during childhood and most have onset before five years of age. By adulthood, majority of these patients will have outgrown AD. Traditionally it is believed to be 70% but more recent data shows this number may be lower. Or a number of patients, 30% of patients who do not outgrow their AD tend to have more severe disease and have more associated atopic condition such as food Allergy & Asthma. The risk factors for more severe disease include early onset and more severe disease at the onset. Research has shown that mutation is related to a more severe disease. Those of us who are clinicians have encountered patients with more severe AD. You can experience that these encounters can be very stressful. It is very stressful for the parents, the child because these patients have not been sleeping well so they are crying, screaming in the clinic. For the clinician involved, it can be a very stressful situation. Parents have many questions and therefore it may be hard to hear the parents because the child is screaming. AD does not only affect the patients. It also affects the family and the caretaker. This has been well documented by the global parents for eczema research. One of the problems with AD is due to the itching and scratching it can lead to the scarring of the skin. Scarring can be significant. These are younger children. In the older children, they may be very conscious about these rashes. They may be bullied or made fun of at school. Many of the older children will wear long sleeves or long pants, even during a hot summer day. Other problems with AD, especially those with more severe AD, infectious complications. This child prevents with lesions on the face. This turned out to be eczema. This child was positive for the virus. The treatment. This rash can also mimic eczema. This is a type of eczema caused by a virus. The diagnostic features that may give it away is the patient may have some rashes on the palms, the soles, and ulcers, so called hand, foot and mouth disease. The treatment is symptomatic. A patient will configure routine eczema care and anti-inflammatory treatment. This is the most common bacterial infection with eczema or AD. Staph. This patient has generalized AD. He does have a resistant staph infection that will require systemic antibiotics. It is important to assess the severity of AD. The severity will dictate the types of treatment. There are different ways you can assess AD based on patient reported outcomes or measures. You can ask about sleep and quality of life, activities, school and work. There are some validated measures that you can use, also. If any of these areas like sleep, activities, school or work is affected, we have a problem. In terms of the clinician measure, it may include global assessment. In general, the IGA, it is easier to use, very simple it ranges from 0 to 4. It is an easy scale to use in the clinic. The EASI and SCORAD are more time-consuming and generally used in research. More clinicians should document a picture of the body or face in the chart. That will help follow-up the progress of the patient. These are the current approved topical treatments for AD.
We will go through each of them one by one. First. In moderate to severe AD, we want to use a mid-potency. This is likely the most common used topical steroid. It comes in large quantities, relatively inexpensive. Regarding proactive versus reactive approach to applying medications. In general, the proactive approach has shown to be effective. However, in real life, it may not be as practical because we are basically telling patients to apply these medications on asymptomatic areas. As we all know, it may be already difficult to get patients to use these medications when they are symptomatic. Personally, I prefer the reactive approach. I have a patient use it as needed. Once or twice a day when they have symptoms. The key here is to apply the medication early during the onset of the rash. I put here the fingertip units. It is a practical and easy way to explain to the parents how much topical anti-inflammatory medication to use. I think this is very helpful sometimes in reassuring the patients and parents they are not over using the medication. You can search how to use fingertip units. This is a relatively common side effect of topical steroids — skin atrophy. In general, a patient will sustain skin atrophy because of long-term use of topical steroids. In general, mid-potency, the side effect from skin atrophy, it is not very common. In the thinner skin areas such as the face, use the non-steroid anti-inflammatory treatments is preferred. In this case, Tacrolimus and Pimecrolimus. These are inhibitors that have been around 20, 25 years. They were given a black box warning regarding cancer. This has been proven by review and analysis there is no association with cancer.
I generally would explain to the parents when I prescribe these medications rather than to have them open the box and discovered himself. Topical JAK inhibitors. Small molecules that block the pathway of what leads to information — leads to inflammation. R uxolitinib is approved in the U.S. Delgocitinib is approved in Japan. These topical JAK inhibitors are labeled with a black box warning that includes a major cardiovascular events such as stroke, heart attack or thrombosis and serious infection. Since these medications are relatively new, even though they are topical, potential side effects warning is needed. Indicated mild-to-moderate AD. Patients who have less than 20% of BSA. There is some uncontrolled study that have used a more severe patient in the study. The systemic level correlates with the amount of the severity of the AD. If used with a more severe patient in that study, it indicates that we have to be more careful in terms of side effects. Based on the farmer go kinetics, it is still below the suppression. Topical PDE4 inhibitors, another class of anti-inflammatory medications. We have Crisaborole, which has been approved since 2016. It has been approved down to six month old for mild to moderate AD. The latest to be approved for topical treatment is the Roflu milast cream, which is also an inhibitor. This is 0.15% and was just approved two months ago down to six years old for mild to moderate AD. I summarized the stage 3 studies in terms of IGA or the number of treated patients. 29% versus the placebo group. For the EASI, 42% in the treated group versus 30% in the placebo group. Roflumilast cream also comes in a lower concentration. It is currently being — studied in the younger group. Here are examples of patients with moderate to severe AD. These patients generally have widespread AD on their body. Many of them, as you can see, have developed consistent, persistent i — persistent itch-scratch cycle. Generally, when a patient has these problems, topical treatment is very challenging in these patients.
Very likely most of these patients will need systemic treatment. The need to understand what causes AD becomes even more important. So we can target the causes and to increase the efficacy and minimize the side effects. On the right you see the environmental triggers. These are not causes but factors that make AD worse. For example, staph on the skin, environmental allergies including a furry pet. Air pollution has been studied in terms of a trigger for AD. The most common trigger in the environment would be humidity changes and temperature changes. AD patients are very sensitive and susceptible to changes in these factors. In terms of causes, the genetic causes for AD, one of the proven causes is a mutation. It is present in some patients. All of the patients with AD have skin defects. All of these patients have deficiency in certain lipids including fatty acid. Skin defects — skin barrier defects are one of the major causes of AD. Some of the prescription moisturizers have not made significant changes in these patients in terms of the more severe patients. Another cause of AD is immune dysregulation. AD patients are more TH2 prone. They have more TH2 inflammation. These are — this is a study from many years ago. They show that AD patients and their lesions, increased expression of IL-4 and IL-13. What do these do? From immunology studies, we know IL-4 is very important. In this case, in predisposed patients or persons to IGE. In AD patients, we tend to see a higher total IgE and more specific IgE sensitization. IL-4 and IL-13 together leads to allergic inflammation. . That is why we see the swelling and the itching. There are other factors that lead to increased production of IL-4 and IL-13. These are mostly produced by the skin cells. TSLP. IL-33 is another keratin. These have been targeted in terms of treatment. So far the clinical studies have not been very successful in terms of treatment of AD and likely because these occur or produced early in the pathway of AD. By the time patients have developed moderate to severe AD, it is too late to target these. Increased IL-22 has also been shown in AD lesions. This is a potential future target in AD. Currently, there are two, and since last week three, Biologics that are approved for AD. Dupilumab has been approved since 2017. It targets the IL-4 receptor. It has been approved down to six months old. Patients with moderate to severe AD. Tralokinumab targets IL-13 and has been approved since 2021 and has been approved down to 12 years old. Just last week we had an anti-IL-13 approved down to 12 years old.
I did not put that here because the slide was made before that. This is one of the crucial studies that led to the approval of Dupilumab. This is a phase 3 study that went on for 52 weeks. Placebo control. As can be seen here, the treated group, almost 70% of patients achieved as compared to the placebo. No difference in terms of efficacy before the groups. Since then, we have had five-year data of Dupilumab study. This just got published. It shows the five-year open label Extension study of Dupilum ab. One of the highlight boxes, by five years, up to 90% of patients continue to obtain EASI -75 from their baseline. A high number maintain a IG of 0-1, which is mild. Over five years, these are the side effects that are shown. A highlighted one of the most common side effects. In the five-your extension study, if you combine them, it is about 20%. In real life, I am observing much less than this 20%. Likely my population is probably mostly younger patients. You have the most severe side effects. Keratitis. That is about 1% to 2%. I had one or two patients would have to discontinue due to a severe condition. The rest of the patients normally can continue. This shows the five-year data on how many of the patients continue to use topical treatment. As seen in the third column, majority of these patients, almost 60%, will still need some treatment with topical steroids or topical inhibitors. This also correlates with my clinical observation to the majority of the patients on Dup ilumab still require treatment with topical anti-inflammatory. These patients’ persistent areas are in the flexor areas. This is another five-year study. It is a study for up to five years in the Netherlands. Up to five years, almost 80% of these patients continue to be almost asymptomatic with an EASI score of less than 7. These patients have either asymptomatic or mild AD. Again, they also show the majority of these patients are still needing some tropical treatment. Up to 80% of these patients are still using some form of tropical steroid — topical steroid. In terms of side effects, in the real life study, according to the data, about 7.6% of patients discontinued due adverse effect and some due to eye disease and some due to joint and muscle pain. Lymphoid reaction, this was shown in a dermatology case series recently that some patients developed so-called CTCL-like lesions. However, on the biopsy, it turned out these patients had a reaction that eventually resolved when the Dupilumab was discontinued. They did find a few that had CTCL but those patients were misdiagnosed for AD and treated with Dupilumab. 6.6% discontinued due to ineffectiveness. That is a little bit higher than what I observed. 0.8% discontinued due to controlled disease. That is an area some of us might have questions. When do the patients stop the medication? T ralokinumab, these are phase 3 study results. A significantly higher number of patients. Those who attain EASI-75, they were randomized and then followed up in week 32. By then, 70% of these patients attained EASI-75. If a patient improves by 16 weeks and attains EASI-75, you can decrease the frequency of the treatment to make it easier for the patient. The graphs show the Tralokinumab have been studied in older adults. I think this could be significant because we know the patients who have failed Biologics, if they need to go on medication like a JAK inhibitor, the age would be a critical factor in terms of the potential side effects. In this case, Tralokinumab is also a factor in — also effective in older adults. These are some of the Biologics in the pipeline. Lebrikizumab got approved. Nemolizumab, which blocks IL-31, it is being evaluated by the FDA regarding approval for AD. the lastTwo, they are anti-OX. These are potential Biologics being studied for AD. Below here, another anti-IL-13 that is in a phase 2 study.
These are some of the crucial phase 3 studies for Lebrik izumab. As can be seen on the graph on the right, almost 59% of patients attained EASI-75. That is similar to Dupilumab as compared to the placebo. The side effects in the 16-week study. Also, interesting just like Tralokinumab and Dupilumab, it has been shown anti-IL-13 and IL-4 medication have shown to decrease bacterial skin infection. One of the benefits of these medications, the TH2 inflammation is predisposed to more infection. Lebrikizumab also has 52-week data. It is very interesting. It provides very useful data. What happens is at 16 weeks, those patients who attain EASI-75, they were randomized to three groups. One group received every two weeks and then another group receives every four weeks of Lebrikizumab. The third group would be placebo. They stop Lebrikizumab once they attain EASI-75. It can be seen here. About 80% of patients continue on Lebrikizumab continue to maintain that EASI-75. Similar maintain the anti-itch affect. The placebo, lower, 66% attained EASI-75 and the anti-itch affect. If you look at it the other way, it is also interesting. By 16 weeks, if they attain EASI-75, about 65% of these patients continue to be OK maintaining their EASI-75. If you look at the EASI ID data, which is also useful, of all the patients who attained EASI-75 at 16 weeks, about 60% of them already had EASI 90. These patients are essentially asymptomatic. At most, a very mild AD. As can be seen, the 40% of these patients who initially had EASI-75 or EASI 90 has mild AD at 52 weeks. Useful data. What are the comparisons between these biologic and immuno modulators? This is analysis that compares. The middle line is Dupilumab. As can be seen , they are more superior with efficacy. Tralokinumab, less effective than Dupilumab. This is a more recent comparison by the same group. That includes Lebrikizumab. Lebrikizumab seems to be equal in terms of efficacy compared to Dupilumab on the middle line. Again, the other systemic will reproduce. In terms of oral JAK, even though our talk today is on biologic, I will mention briefly these medications. The control study of 12-20 weeks with placebo control shows there is a higher rate of side effects in terms of nausea, acne. That is compared to placebo. Regarding the side effects on the blackbox warning such as major cardiovascular events, thrombosis or severe side effects, infection, there was no difference between the treated group and the placebo group. Therefore, for short-term use, I think these medications remain a viable alternative for patients who are not able to use Biologics. In long-term use, we need to continue to monitor current data. It suggests age in terms of patients older than 55 or 65, especially a patient with risk factors, they are more susceptible to those side effects. The topical treatment in younger children, Biologics may be effective but are not always the easiest medications to use. Injections. Not most friendly to children.
Topical treatment remains to be pursued. One of the medications, Tapinaro f, a receptor that increases the skin barrier and that has been evaluated by the FDA for treatment. Topical is also important. We will see more of these treatments coming in the pipeline. Similar molecules including PDE-4 inhibitor and also topical probiotics, also an interesting area of study. The prevention of dermatitis in young children. We have seen some studies attempting to use moisturizer early in high risk babies to present AD. However, what is unknown at this point is the type of moisturizer and the timing that’s the moisturizer should be applied to the skin to prevent AD. There are also studies using topical anti-inflammatory medication. Probably in the future, systemic. However, these medications can be associated with potential side effects. Therefore, we need a very accurate method to measure, to predict which babies with AD. The skin tape method has been used because it is noninvasive. There are other methods in the pipeline. I think that is the end of my talk. Back to the moderator. AD thank you.
Catherine: Thank you. I was struggling to find my audio button. Thank you, Dr. Ong, that was very informative. A lot of good information. We have some questions in the chat that I am going to go over. One of the questions was, as a side effect when the skin gets thin with the atopic dermatitis and the person wants to know whether that is a permanent side effect or does it get better?
Dr. Ong: It depends on the severity. The majority of the patients, in general, usually it is not reversible in most patients who are more severe.
Catherine: OK. Thank you. You showed a lot of pictures with the severity of atopic dermatitis in children and how sometimes the lesions came upon scratching. For a pediatric patient, but has to be tough. You tell them to stop scratching and they just do not do that. How would you guide the parents and having them may alleviate the itching? Is there any kind of ointment you would recommend?
Dr. Ong: The itch-Scratch cycle is one of the toughest areas to treat. I always tell patients, talk to parents regarding this problem. We can treat a rash easily with medication. But once they develop the habit to scratch — it is not their fault, it is an automatic reaction and it is continuous. This is one of the biggest challenges in terms of treating, in this case, in children. In the adults, also, the itch can be very challenging. We do not have very good treatment at this point in terms of systemic treatment. We still use medication to help them sleep better.
Catherine: Another question that just came in — this person has a child which appears to be bruising under the eczema patches. Is this normal or common? What advice can be given to the child’s parents for this?
Dr. Ong: If this happens consistently, meaning every scratch leads to bruising, I would definitely talk to the physician and see if they can do some blood tests to make sure we are dealing with atopic dermatitis because there are other forms of eczema.
Catherine: OK. Sometimes, atopic dermatitis affects the feet. The question was, would you recommend wearing cotton socks? What would you recommend if they were having trouble walking?
Dr. Ong: If they have trouble walking, at a severity level, if that is the main area being affected, I would increase the intensity of anti-inflammatory treatment in that area. I did not mention an acute treatment that we use. Topical steroid in the area. In this case, you can put a wet cotton sock and cover it with another dry layer of cotton socks. Sometimes over a few hours, over several days, that can heal the inflammation much faster.
Catherine: OK. Very good. I think we got to all of the questions in the question and answer in the chat, so I just want to thank you, Dr. Ong. This has been very informative. This is the first time I have seen the severity of atopic dermatitis in pediatric patients. I have never seen it that bad. It is a serious condition. I want to let the audience know we have a few webinars coming up. We will welcome Melissa Page. They will discuss the training program on September 24 at 12:00 p.m. Eastern standard Time. On October 16, Dr. William Berger will discuss meeting the needs on the patient journey at noon Eastern standard Time. You will receive an email from Zoom in a few days with a link to the recording, an evaluation and additional resources. Thank you so much from the Allergy & Asthma Network. Join us as we work every day to breathe better together. Enjoy the rest of your afternoon and thank you for joining.
