Linda Stocum

 How does the approval for dupilumab [Dupixent; Sanofi and Regeneron Pharmaceuticals, Inc] in the 6 months to 5-year age group change the pediatric atopic dermatitis [AD] treatment space?

Amy Paller, MD, chair of the Department of Dermatology at Northwestern University’s Feinberg School of Medicine:

 We have been so fortunate to have a medication that has such a great safety profile, and yet does a wonderful job just as well, if not better than what we've seen before with other immunosuppressants for children. As we get younger in age, we can have [severe cases of AD in] children. Not only is it wonderful to have that kind of safety, where we don't even have to draw labs, but we could be resetting their immune system towards a more normal life, maybe even preventing the development of some of the comorbidities [associated with AD] in addition to making their quality of life [QoL] and their families [QoL] better.

 How does the mechanism of action in this treatment work in this young population?

 It works, as far as we know, just as it does in any other population. The mechanism of action, of course, is inhibition of [the interleukin (IL)-4 and IL-13] receptors. Since there's such a dynamic interplay between these signals, and everything that we see in [AD], whether it's the itch, the thickening of skin, [or] potentially even some relationship to the development of comorbidities. We really don't understand [the relationship to comorbidities] well. But as you can imagine, if you can block the signal that really increases levels of cytokines and chemokine, not only in the skin, but in the blood as well, then, we're hopefully dialing down signals that ultimately cause damage.

 Were there any adverse events more prevalent in this patient population?

 No, that's why [dupilumab is] so exciting. We certainly didn't see anything that we've not seen before. There are low rates of everything. The only [adverse events] out there were injection site reactions, but that wasn't terribly different. [There was a] very low risk of [injection site reaction]. [The greater adverse event] was conjunctivitis, but again, very low risk.

 How does the dosing work? Is it the same loading dose process as the other pediatric patients that are already approved to take this?

 There is no loading dose. So, it's a single injection. Other patients do get a loading dose, but not so with this age group in the studies. It’s good to know that's not needed. Secondly, we have to teach the parents how to give the injections and do things that are comforting to the babies. It's like giving any kind of a vaccine in the younger children, we try to have them sitting upright in the parent’s lap in a comfortable, not restrictive position so that they don't get scared and trying to do something with them that is disrupted.

We have tricks that can be used to create decent tactile stimulation near the area where the injection is going in. We have a lot of tricks up our sleeves that we can use in younger children to try to help them to have less pain with this very short injection.

I can't wait for the day when the pen form [of dupilumab] is available in the younger patients. Right now, it's only available for 12 years old and older. [In the pen form] there is no needle to be seen, it takes less time, and it’s superior because a lot of parents know about epi pens already.

 And what happens if a patient's parents wants or needs to discontinue treatment for their child?

 Well, I think this is an interesting age group for that question. Usually, we're talking about adolescents who've had [dupilumab] for years, and oftentimes, it's probably not going anywhere fast. Especially once we get to about 10 years of age, with these young children, that's not necessarily the case.

I have a lot of excitement about the potential for resetting, with some very aggressive management, those [patients] who don't respond to the topical therapies very well. We see the possibility that when they're very young, with suppression for a period of time, maybe they won't need it [for as long.] We don’t know that there's no studies to that, but we might rethink a little bit this concept of having to do this very long term. That said, I probably personally, would keep [a patient] on it for at least several months.

The older children, we always say at least a year, maybe even 2 [of active treatment]. [This will] give the family a break, [increase] quality of life, make sure to give them enough time to really get away from their [AD]. It’s a terrible effect on their life that occurred before starting the dupilumab.

In this case, “I would probably say ‘were going to have to get some experience.’” But like with older children, after a period of time, and maybe that's going to be 6 months, rather than a year or 2, I would start to space out of bit from every 4-weeks to perhaps every 5-weeks, every 6-weeks, whatever it might be, and just see if they're flaring. Obviously, if a baby is doing quite well on the dupilumab, but still has disease activity, you're not going to do well to stop the medication. On the other hand, somebody who's clear or very close to clear, I think it is a good idea to try to space out. If things go well try to stop it and control [the AD] with topicals that we couldn't use before, or maybe not even need anything at all.

 Would this be able to be used in combination?

 The studies were done with topical steroids in this [6 months to 5 years] group, as well as in the age group of 6 to 11. We do have some experience with topical steroids. It's going to be an individual [patient treatment recommendation]. I know there are going to be many children who don't need topicals at all.

You wonder, “do you want to continue with the systemic?” I think, in my own experience, that if a physician is having to put a medium strength or higher topical steroid on someone at least once a day, and not seeing clearance, think about moving to something that's relatively safe and can give [the patient] better results. There is a significant burden with trying to put on topical steroids, sometimes twice a day, and all the routine that goes with that. When somebody is putting on daily, at least a medium string steroid ointment they are getting absorption. We know they're getting some absorption and that hasn't been well studied. But I do worry about that.

I really think carefully about that and using shared decision making with the family to decide whether it's worth trying to [try another medication], even if there can be at least partial control with a medium strength or more potent tropical steroid.

: Are there any concerns about insurance cost or availability?

 Access is the biggest issue we have. These are expensive medications and we as caregivers have to keep that in mind. Not just for the individual patient, but for society as a whole. We can't put everybody with [AD] on a medication that costs several 1000’s of dollars every year. That said, we don't want to withhold that from someone who really could have a much better life using the medication. So, that's part of being a physician. We have to make these kinds of decisions.

Fortunately, in patients who are deserving based on the severity of their disease, when one has tried other medications, and particularly topicals, we've been largely able to get it for these patients. Of course, it has to be on label, and we do have to try the whole series of topicals. Even if we think from the start, that it may not work. In this particular age group [of 6 months to 5 years], I have been very gratified by the large number of patients who come in with severe [AD], particularly in the first year or 2 of life, whom I can manage beautifully with topical steroids and often really dialed down their need, after hitting them hard with fairly aggressive management, and getting that under control.

 And is there anything else that you'd like to add about this at all?

 I think that the important point is that parents are very worried about the children. [AD] is a horrible disease. Can you imagine having such sleep disruptions? [Patients] scratching all the time creating infections on the skin. [It can] really disturb their ability to develop socialization skills, their ability to sleep, their mental health, there's much more anxiety and depression, even at young ages.

It's gratifying to have something that is safe [and] doesn't even require lab testing that we can introduce, when it's appropriate. Making the decision about when it's appropriate is a tough one because nobody wants to give a child, especially in this age group, shots. That causes pain for anyone. We don't have any way to totally eliminate that pain, even if we put on a topical anesthetic.

So, I think we have to be grateful, because the injection is only every 4-weeks and recognize that it's critically important regardless of [its potential pain], to utilize a relatively safe medicine, and improve somebody's life.

Originally published on our sister brand, 

Articles

Amy Paller, MD, sits down to answer important questions on the FDA approval of dupilumab for patients aged 6 months to 5 years.

An inside look on the dupilumab approval

The FDA has approved dupilumab (Dupixent; Sanofi and Regeneron Pharmaceuticals, Inc) for children aged 6 months to 5 years with moderate-to-severe atopic dermatitis (AD) whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable, according to a press release. This filing is also under review by the European Medicines Agency (EMA) for this age group along with and submissions to regulatory authorities in other countries worldwide. Dupilumab is a fully human monoclonal antibody that inhibits the signaling of the interleukin (IL)-4 and IL-13 pathways and is not an immunosuppressant.

The president and CRO of the National Eczema Association, Julie Block, commented on the approval and said, “moderate-to-severe atopic dermatitis in babies and young children is more than just a rash – the intense itch can make them scratch uncontrollably throughout the day and night and cause their skin to crack and bleed.” She continued, “caregivers do their best to manage skincare routines multiple times a day, but for many, topical treatments are not enough. We’re pleased to see how scientific innovation and research continues to address unmet needs for the atopic dermatitis community, and we’re hopeful for the positive impact Dupixent can have for these children and their families."

Most patients, 85%-90%, first have AD symptoms before the age of 5 years, which often affect them into the later years of their lives.

submitted for priority review from the FDA, which was accepted in February 2022,

 and had an original target action date of June 9, 2022.

The approval was supported by data from the 

 a phase 3 trial evaluating dupilumab every 4 weeks (200 mg or 300 mg, based on body weight) plus low-potency topical corticosteroids (TCS) or TCS alone (placebo) in pediatric patients aged 6 months to 5 years with uncontrolled moderate to severe AD. The trial met all primary and secondary endpoints.

The analysis found that at 16 weeks patients treated with dupilumab:

Twenty eight percent achieved clear or almost-clear skin compared to 4% with placebo;

fifty three percent achieved 75% or greater overall disease improvement from baseline compared to 11% with placebo;

seventy percent average improvement from baseline in EASI 75 compared to 20% improvement with placebo;

forty nine percent average improvement from baseline in itch compared to 2% improvement with placebo; and

significantly improved measures of observed patient outcomes (including sleep, skin pain and health-related quality of life), as well as caregiver-reported health-related quality of life.

The data found that the safety profile in this trial was like the safety profile in patients 6 years and older with AD. The long-term (52 weeks) safety profile of patients receiving active treatment found it was also consistent. The most common adverse event was hand-foot-and-mouth disease and skin papilloma reported in 5% and 2% of patients treated with dupilumab aged 6 months to 5 years, respectively, and none of these cases led to treatment discontinuation.

“This approval is a tremendous advancement for children as young as six months old with moderate-to-severe atopic dermatitis, as there is a large unmet need in this population and we’ve seen what Dupixent can do for older children and adults with this disease,” said Mercedes E. Gonzalez, MD, FAAD, pediatric dermatologist at Pediatric Dermatology of Miami. “Dupixent is a very welcome addition to our treatment options, which up until recently, primarily included potent topical steroids. Now we have something that targets an underlying cause of the disease, and may change the trajectory of their childhood by removing the burden of moderate to severe eczema from their lives, hopefully making the future brighter for these children.”

Press Release: FDA approves Dupixent® (Dupilumab) as first biologic medicine for children aged 6 months to 5 years with moderate-to-severe atopic dermatitis. GlobeNewswire News Room. Published July 6, 2022. Accessed June 8, 2022. https://www.globenewswire.com/news-release/2022/06/07/2458243/0/en/Press-Release-FDA-approves-Dupixent-dupilumab-as-first-biologic-medicine-for-children-aged-6-months-to-5-years-with-moderate-to-severe-atopic-dermatitis.html

Sanofi and Regeneron Pharmaceuticals, Inc announced the FDA approval of dupilumab. It is now the first biologic medicine for children from 6 months to 5 years old with moderate to severe atopic dermatitis.

Dupilumab FDA approved for AD patients 6 months to 5 years

Sexually transmitted diseases and infections (STDs/STIs) are common health issues in the United States, according to Kenneth J. Tomecki, MD, staff physician in the department of dermatology at the Cleveland Clinic, and past president of the American Academy of Dermatology.

 He cited 2018 data from the Centers for Disease Control and Prevention (CDC) that revealed 1 in 5 people in the United States had an STI. In that year alone, there were 26 million newly acquired STIs, nearly 50% of which were acquired by people aged 15 to 24 years. Nearly $16 billion was spent on direct medial costs.

In light of these statistics, it is important that physicians expand their knowledge about different STDs and how to treat them, Tomecki said.

Tomecki ended his presentation with key facts about the STDs/STIs in 2022

There are 1 million STIs acquired every day worldwide, with most patients being asymptomatic,

Each year there are an estimated 374 million new infections, with one fourth of STIs being chlamydia, gonorrhea, syphilis, and trichomoniasis,

More than 500 million people 15 to 50 years old are estimated to have genital HSV infection and up to 1 million pregnant women had syphilis as of 2018,

There are as many as 350,00 adverse outcomes

The drug resistance of these diseases is increasing, notably in gonorrhea

Tomecki reported no relevant disclosures.

Tomecki, K.STDs: the dirty half dozen. Presented at: 2022 Fall Clinical Dermatology Conference for PAs & NPs; June 3-5, 2022 Scottsdale, AZ and virtual.

CDC newsroom. CDC. Published January 25, 2021. Accessed June 3, 2022. 

https://www.cdc.gov/media/releases/2021/p0125-sexualy-transmitted-infection.html

Sexually transmitted infections (STIs). Accessed June 3, 2022. https://www.who.int/news-room/fact-sheets/detail/sexually-transmitted-infections-(stis)

Kenneth J. Tomecki, MD, discussed the clinical relevance of sexually transmitted diseases to dermatology and outlined what to look for and how to treat various conditions at the 2022 Fall Clinical Dermatology Conference for PAs & NPs.

STDs and dermatologic symptoms

Acne vulgaris is a skin condition caused by the dysfunction of the pilosebaceous unit which causes red bumps on the face and truck. Commonly, adolescents battle with this skin condition, but this patient age group is also more susceptible to misinformation. A recent article looked into the issue of the amount of misinformation on the internet by compiling a qualitative review of misinformation and conspiracy theories in acne.

The reason why adolescents are often more likely to believe misinformation is due to age, stress about the condition, and the amount of time spent on the internet. The researchers performed a review in March 2022 of PubMed that used the terms ‘acne’ AND ‘misinformation’ OR ‘disinformation’ OR ‘conspiracy theory’ in which 1,024 abstracts were found and then analyzed to see if they should be included as misinformation. After the analysis, 5 were included. After, a Google search was conducted using combinations of the terms ‘acne’ and ‘misinformation’, ‘disinformation’ and ‘conspiracy theories’. After that, TikTok, Twitter, Facebook, and Instagram were also investigated.

The common categories of the false content were diet and other ‘causes’ of acne, distrust of traditional acne therapies, and the use of nonconventional treatments. The dietary causes of acne, in these misinformation posts, included exposure to dairy products, high-fat foods, and chocolate. Other supposed causes included poor hygiene, contagion, systemic infections such as Candida, and fluoridated water, the researchers explained. For cures, veganism was often cited along with natural topical treatments, and nutritional supplements like diindolylmethane.

The posts said treatments like antibiotics were poisonous, and isotretinoin was toxic and devasting to the patient. Other misinformation about common treatments included an over exaggeration of cases of depression, inflammatory bowel disease, organ failure, infertility, and sexual dysfunction.

The researchers found that the websites in which these pieces of content were found often were associated with companies that were selling products that were advertised to cure acne in a short amount of time.

“Dermatologists should be aware of the nature of acne-related misinformation available online, and be prepared to counter it with scientific principles and facts,” the researchers concluded.

O’Connor C, O’Grady C, Murphy M. Spotting fake news: a qualitative review of misinformation and conspiracy theories in acne vulgaris. 

. Published online April 18, 2022:ced.15222. doi:10.1111/ced.15222

Teenagers were the most likely to be affected by targeted misinformation.

Misinformation and acne

Most children will break out in/develop a rash at some point, but commonness does not make these skin conditions any less irritating or, in some cases, painful. Rashes are often caused by eczema or allergic contact dermatitis, which while similar, can be treated differently and recognizing the differences and causes is essential to making a correct diagnosis—the key to proper treatment and, ultimately, relief, according to JiaDe Yu, MD, FAAD.

Yu, director of the Contact Dermatitis and Occupational Dermatology Clinic and an assistant professor of adult and pediatric dermatology at Massachusetts General Hospital in Boston, detailed the fundamentals and latest approaches for both skin disorders in a presentation on pediatric AD at the 2022 American Academy of Dermatology Annual Meeting in Boston.

Eczema is frequently characterized by intense itching, which can damage skin and worsen the rash. AD is the most common form and typically presents early in life, with most patients developing the condition before their fifth birthday. Eczema can appear differently on skin of color—an important point because Black and Asian American children develop AD more often than their White counterparts, and Black children potentially have itchier, more severe eczema.

Eczema may resolve as a child grows up, but 50% of patients still will have it when they reach adulthood. Although there is no way to know if the condition will persist, early diagnosis and treatment can prevent severe disease, which can be harder to treat and is more likely to continue into adulthood.

Although it can be confused with eczema, allergic contact dermatitis can generate symptoms such as rash, tenderness, burning, and blisters. Metals such as nickel and cobalt, which can be found in toys, clothing accents, and costume jewelry, are likely allergens among children. Soaps, shampoos, and laundry detergents are sources of 2 other common allergens: fragrance and preservatives. Chemicals and dyes used to treat fabrics can also induce a reaction.

“Dermatologists are seeing 2 emerging allergens affecting children—adhesive allergens, which are commonly used in wearable blood glucose monitors, and acetophenone azine, linked to reactions associated with…an allergen from a chemical used in shin guards and footwear,” Yu noted.

Knowing a rash’s location and getting a thorough family history of skin conditions can help differentiate the conditions. Allergic contact dermatitis often arises in unusual locations—say, fingertips, eyelids, or lips—whereas eczema frequently presents on areas such as the wrist or back of knee. Because allergic contact dermatitis worsens eczema, children who have eczema should avoid common allergens when possible.

Yu suggested referring patients to a specialist for patch testing because it can reveal allergic contact dermatitis. “Patch testing is the gold standard for detection of allergic contact dermatitis in adults and children,” he said. “It is the belief of contact dermatitis experts that patients should be patch tested before starting a systemic immunosuppressive agent such as methotrexate, cyclosporine, [or] dupilumab [Dupixent; Sanofi and Regeneron Pharmaceuticals]…due to the potential for ‘curing’ their dermatitis with allergen avoidance alone.”

Approximately 40% of pediatric patients with AD have a relevant positive allergen that may contribute to their dermatitis, Yu continued. Lack of awareness of the potential allergen can lead to unnecessary long-term treatment with topical steroids or systemic immunosuppressants.

Dermatologists have a wide range of choices for treatment. Although dupilumab has shown efficacy for AD in the pediatric population, Yu said, some patients fail treatment. In these cases, options include tralokinumab (Adbry; LEO Pharma)—the agent specifically binds to and inhibits the cytokine IL-13—and Janus kinase (JAK) inhibitors such as abrocitinib (Cibinqo; Pfizer) and upadacitinib (Rinvoq; AbbVie). Upadacitinib is FDA approved for patients 12 years and older with moderate to severe AD, whereas abrocitinib is approved only for adults.

According to Yu, tralokinumab has an adverse event (AE) profile similar to that of dupilumab, but JAK inhibitors are still being explored.

“In children, we always try to be more cautious, and therefore most pediatric dermatologists would likely offer safer treatment options like dupilumab or tralokinumab prior to novel JAK inhibitors until more is known about the [AE] profiles in children with atopic dermatitis,” Yu said.

The drugs’ ease of dosing and delivery is an important discussion point with patients. If a therapy requires multiple doses a day, adherence may be difficult; if it causes pain, the patient may be resistant. “In my experience, once children see the significant benefit a particular medication has on their skin, they are more likely to adhere to the dosing regimen,” Yu said.

In addition to allopathic medicine, which is a system in which physicians and other healthcare professionals treat symptoms and diseases using drugs, radiation, or surgery, alternative regimens may benefit pediatric patients with eczema, according to Yu. Integrative approaches to consider, in his view, include acupuncture, behavioral therapy, and relaxation techniques, which may help reduce stress, a factor that worsens eczema and AD. For at-home help, apps such as Calm can Headspace offer breathing exercises, but these may not be as suitable for younger patients.

“Natural therapies such as sunflower oil, extra virgin coconut oil, and safflower oil have the most evidence for being effective,” Yu said. “However, I make sure to avoid products for which I don’t know the ingredients, given risk for contact dermatitis.”

This article was originally published by sister publication Dermatology Times.

1. What’s causing your child’s itchy rash? American Academy of Dermatology. March 25, 2022. Accessed March 26, 2022. 

https://www.aad.org/news/cause-childrens-itchy-rash

2. Kaufman B, Alexis A. Eczema in skin of color: what you need to know. National Eczema Association. February 16, 2018. Updated July 15, 2022. 

https://nationaleczema.org/eczema-in-skin-of-color/

3. Reeder M, Atwater AR. Acetophenone azine: The 2021 American Contact Dermatitis Society allergen of the year. 

 2021;107(5):238-240. doi:10.12788/cutis.0252.

4. U.S. FDA approves Rinvoq (upadacitinib) to treat adults and children 12 years and older with refractory, moderate to severe atopic dermatitis. AbbVie. Press Release. Published January 14, 2022. Accessed January 17, 2022. 

https://news.abbvie.com/news/press-releases/us-fda-approves-rinvoq-upadacitinib-to-treat-adults-and-children-12-years-and-older-with-refractory-moderate-to-severe-atopic-dermatitis.htm?view_id=6943

5. Breaking news: FDA approves Cibinqo (Abrocitinib). National Eczema Association. Published January 14, 2022. Accessed January 17, 2022. 

https://nationaleczema.org/cibinqo-approval/

Allergic contact dermatitis and atopic dermatitis are common causes of rashes in the pediatric population. Patch testing can help demystify the cause of such skin conditions and determine treatment. 

Using integrative, allopathic approaches to treat atopic dermatitis

The American Academy of Dermatology (AAD) has released their survey results of more than 1,000 Americans. The Academy found that responders did rate themselves higher for sun protection and said that sun protection is more important to them now than 5 years ago. However, many have a lack of knowledge on how to protect themselves from the sun and the risks of sun exposure, like skin cancer.

Other results include, 62% of responders rating themselves an overall grade of excellent or good for sun protection in 2021, but 63% reported getting a tan, which is an increase of 9% from 2020. About 30% of survey takers reported getting a sunburn, which is an increase from 25% in 2020.

“If you are getting a tan, you are definitely not doing a good job of protecting yourself from the sun,” said board-certified dermatologist Mark D. Kaufmann MD, FAAD, president of the AAD, in the release. “There is no such thing as a safe tan. Every time you tan or burn, you are also damaging the DNA in your skin. The more you damage your DNA, the greater your risk of getting skin cancer.”

Other misconceptions the survey found were:

Responders believing that SPF 30 is twice as protective as SPF 15 (67%)

Often forgetting to reapply sunscreen (65%)

Unaware that shade protects a person from UV rays (43%)

Patients understanding the difference between SPF numbers and what the measures mean is an essential part of sun protection. The AAD recommends that everyone, in order to reduce the risk of skin cancer, should seek shade, wear sun-protective clothing, and apply a broad-spectrum, water-resistant sunscreen with an SPF of 30 or higher.

“It’s great that 82% of respondents say protecting their skin from the sun is more important to them now than it was five years ago,” said Kaufmann in the release. “However, it’s important that people use sun protection now so they can prevent premature skin aging and reduce their risk of skin cancer before they start seeing the damaging effects of the sun on their skin.”

As a way to help educated the public, the AAD will be starting its SPOT Skin Cancer campaign on May 2nd, Melanoma Monday, as May is melanoma awareness month. The Academy has also awarded 20 shade structure grants to public schools and non-profit organizations this year for the installation of permanent shade structures for outdoor locations that are not protected from the sun, such as playgrounds, pools, or recreation spaces, according to the release. Since the start of the Shade Structure Grant program in 1999, the Academy has awarded 480 shade structure grants that protect an estimated 3.6 million people from overexposure to the sun each day. The AAD also has a youth education program called the Good Skin Knowledge, that teaches common skin, hair, and nail conditions to children and adolescence.

“As we head into summer, it’s important that the public practices safe sun to reduce their risk of skin cancer,” Kaufmann concluded. “If you have any questions about how to protect yourself from the sun or notice new or suspicious spots on your skin or any spots that are changing, itching or bleeding, make an appointment to see a board-certified dermatologist.”

New American Academy of Dermatology survey reveals most Americans say sun protection is more important now than five years ago, yet many misunderstand how to protect themselves. April 26, 2022. Accessed April 28, 2022. 

https://www.aad.org/news/new-aad-survey-reveals-growing-importance-sun-protection

The American Academy of Dermatology’s survey finds more Americans say sun protection is more important than 5 years ago, but don’t understand how to protect themselves.