The Economics of Atopic Dermatitis: From Real-World Burden to Value- Driven Treatment Strategies

In a recent American Journal of Managed Care® Peer Exchange, a panel of experts examined the clinical role and benefits of topical therapies in managing atopic dermatitis (AD) in pediatric patients and strategies for delaying the need for biologic treatments. The panel addressed how to navigate the current treatment landscape, patient education, and patient-centered care strategies. They also discussed the potential cost savings and health care resource optimization achieved through effective use of topical treatments in AD management. The session was moderated by Brian Keegan, MD, PhD, FAAD, a dermatologist at Princeton Dermatology in Princeton, New Jersey.

Challenges of AD Treatment

AD, also known as eczema, is a common, chronic, inflammatory disorder that causes skin barrier dysfunction, intense itching, lichenification, and an increased risk of cutaneous infections.1 AD affects up to 20% of children and 10% of adults in high-income countries and has a usual age of onset of 3 to 6 months.1-4 AD affects approximately 204 million people worldwide, of whom half are children.5 AD is the leading cause of the global burden of skin disease, and recalcitrant AD symptoms have a substantial psychosocial impact on patients and their relatives; they are associated with an increased risk of comorbidities such as attention-deficit/hyperactivity disorder (ADHD), other atopic diseases, food allergies, and mental health disorders.1,5 AD has a considerable impact on quality of life beyond the hallmark symptom of pruritus, including pain, sleep loss, anxiety, and depression.6 Patients can experience frequent secondary bacterial infections, particularly recurrent staphylococcal infections that complicate treatment regimens and increase health care utilization.1

AD is heterogeneous in terms of clinical features, severity, and course.1 Diagnosis is based on clinical signs, and a clinician’s assessment is considered the gold standard.1 Core features of AD are eczematous lesions, intense pruritus, and a chronic or relapsing disease course. Other common features are generalized skin dryness (xerosis), early disease onset, and a personal and/or family history of atopic disease (eg, asthma, allergic rhinitis, AD) or specific IgE reactivity.1 In infancy, AD often presents as acute lesions characterized by poorly defined erythema with edema, vesicles, excoriations, and serous exudate.1 These lesions typically involve the face, cheeks, and trunk but could be widely distributed.1 In children 2 years and older, eczema typically becomes more localized and chronic than in infancy, characterized by paler erythema, xerosis, and poorly defined lesions that commonly affect the flexor surfaces, accompanied by lichenification in chronic areas.1 AD flares are common and often triggered by environmental allergens such as clothing, sweating, shampoo, house dust mites, pollens, or animal allergens.1,7 Flares and exacerbating factors are common concerns for children with AD and their parents.7

Current treatment strategies include topical treatments in mild to severe AD and systemic treatments in moderate to severe AD.8 Topical treatments include prescription moisturizers, corticosteroids, calcineurin inhibitors, PDE4 inhibitors, and Janus kinase (JAK) inhibitors.8 Most of these can be used from age 3 months and older.8 Systemic treatments include the biologics or monoclonal antibodies dupilumab (6 months and older) and tralokinumab (12 years and older), which are considered in patients who are refractory, intolerant, or unable to use high-potency topical treatment.8 

AD is chronic and complex in nature and requires a holistic approach with multidisciplinary management.9 Patients with moderate to severe AD have an additional disease burden due to comorbidities, including asthma, allergies, and neuropsychiatric disorders.9 Depending on symptoms and comorbidities present, a multidisciplinary care team, led by a dermatologist, may include an ear, nose, and throat (ENT) specialist; an allergist; a respiratory medicine specialist; a gastroenterologist; an ophthalmologist; a dietitian; a rheumatologist; a psychologist; and/or a psychiatrist.9

The American Academy of Allergy, Asthma, and Immunology/American College of Allergy, Asthma, and Immunology (AAAAI/ACAAI) Joint Task Force consulted a multidisciplinary guideline panel consisting of patients and caregivers, AD experts (dermatology and allergy/immunology), primary care practitioners (family medicine, pediatrics, internal medicine), and allied health professionals (psychology, pharmacy, nursing).8 They recently published a good practice statement that, before clinicians issue any new therapy, they should ensure the correct diagnosis and identify complicating diagnoses, provide education (eg, an information guide about the disease and an action plan), address trigger avoidance, ensure proper medication use and adherence, and encourage application of a bland moisturizer titrated to symptomatic benefit (at least once but often multiple times per day).8 Furthermore, they stated that, based on evidence from systematic reviews and a recent large, randomized trial, the best moisturizer is the one that patients will use regularly, and shared decision-making should express the potential trade-offs between benefits (eg, greater benefit with ointment-based moisturizers for more severe disease) and acceptability.8

Stakeholder Insights

“I have a lot of parents [who] come in and [are] afraid of the diagnosis because they don’t want something to be wrong with their child,” said Alexa Hetzel, MS, PA-C, a physician assistant at Schweiger Dermatology Group in East Windsor, New Jersey. “But their skin is failing them, so they can be a little more hesitant to being treated.… Our adolescent population is challenging, too, because they want the immediate response.… Social media has taught them that they can get instantaneous results, and that’s not how things happen. They also aren’t always the most [adherent]. I’ve had kids come in, and they’re hiding medicine under the bed. I’m like, ‘Just tell me how you’re doing. How can I help you?’ So sometimes even the communication between them can be challenging, as well…. We also have limitations in getting these medications to these patients sometimes because they’re not always indicated for this population, so sometimes maneuvering around some of the insurance issues can also be challenging.” Hetzel added, “We’ve all had patients come into our rooms with bags of topicals that they’ve tried…and somebody tries to give them something new, and it doesn’t work as well. And that tachyphylaxis is so real, and they want something ‘stronger,’ right? But is that really what we want? Is stronger the right word, or [is] something different the right word?”

“It’s important to say it’s a chronic condition,” said Vikash S. Oza, MD, director of pediatric dermatology at NYU Langone Health in New York, New York. “Eczema is not a 1- or 2-week issue that you have for your child. This is something that, for many families, they’re going to be dealing with for years on end.… I think part of the hesitation is [that] it’s the first experience a parent has of dealing with a potential chronic medical issue with their kid or their first medical issue with their kid.… We have a public perception of what eczema is, but it’s not getting appropriate therapy for eczema.… But what does it mean to have scratched, open skin? That is a nidus for infection, and that could have a significant impact on a child’s health, having recurrent bacterial or viral infections.… The experience of eczema is persistent itch.… It’s not just severe itch; it’s [also] sleep loss…that really impacts quality of life. So, for a kid, if you could imagine not having appropriate sleep during early development, that’s where we have epidemiologic data to bring up what we call externalizing behaviors when you get older. These are higher rates of ADHD…anxiety…depression. All of these have a global impact on a kid’s health.… So, there’s a lot of hope that if we can control eczema very early on in life, we also potentially have the opportunity to prevent other really large health problems for the health care system and for those patients.”

“I think atopic dermatitis is best managed effectively when you have a multidisciplinary team,” said Amy Spizuoco, DO, FAOCD, dermatologist and dermatopathologist at True Dermatology in New York, New York. “It starts with the dermatologist or the dermatology provider being able to diagnose the kids, adults, adolescents…then also referring to other specialties that play a role, such as an allergist to work them up for allergic rhinitis or asthma, even possibly bringing [in] an ENT if that is [needed]. It’s also great to have your pharmacist and your pharmacy that you work with, so we know that these patients can get those medications that they need. Also…there’s such a heavy burden on the entire family: the parents applying medications, the kids waking the parents up because they can’t sleep, asking them to apply medications, leaving work early to pick up their kid from school because their kids just can’t focus and may be a little rambunctious or are suffering from [an] asthma attack due to their atopic dermatitis condition. So, a lot of times you need to bring in a behavioral therapist to help the whole family learn how to deal with this burden.… A lot of patients don’t have access to care, so it’s sometimes important to bring in some social workers [who] can also assist when the pharmacy can’t help.”

Treatment Strategies for AD in Pediatrics

Optimal AD management centers on maintenance skin care and topical medications to minimize flares and improve quality of life.10 Pharmacological therapies are initiated when nonpharmaceutical treatments, such as emollients with wet wraps, elimination of triggers, changing scratching habits, and psychological interventions, are not sufficient in relieving AD symptoms.8,11 Guideline recommendations by the American Academy of Dermatology and the AAAAI/ACAAI consider topical corticosteroids (TCSs) as first-line treatment for AD.8,12 However, steroid-sparing options, including calcineurin inhibitors, PDE4 inhibitors, and JAK inhibitors, are becoming mainstays in therapy, underscoring the importance of careful selection and use of TCSs to minimize adverse effects.8,12

TCSs are approved in individuals ages 3 months and older.8 They are effective in reducing inflammation and pruritus and preventing relapses, and maintenance therapy is recommended to prevent relapses.12 ​Adverse effects include skin atrophy, increased vascularization, and rare systemic effects like hyperglycemia and hypertension with high-potency TCSs.12 The use of medium- or high-potency TCSs in sensitive areas such as the face, periocular area, groin, and skin folds should therefore be minimized.12 Tacrolimus ointment (0.03% and 0.1%) and pimecrolimus cream (1%) are approved for individuals ages 2 years and older and 3 months and older, respectively.8,12 ​They are effective for acute and chronic AD, especially in sensitive areas such as the face, skin folds, and genitals. Tacrolimus is preferred for moderate to severe AD, whereas pimecrolimus is used for mild to moderate cases. Adverse events include burning and itching upon application, rare allergic reactions, and a black box warning for potential malignancy risk.12 Crisaborole ointment (2%), a PDE4 inhibitor, is approved for individuals ages 3 months and older, and roflumilast is approved for individuals ages 6 years and older; both are effective for reducing inflammation and pruritus in mild to moderate AD.8,12,13 Adverse effects are mild and may include application site pain, irritation, stinging, and burning.

Ruxolitinib cream (1.5%), a JAK inhibitor, has recently been approved for patients aged 2 to 11 years, having previously been approved for those 12 years and older.12,14 ​It is effective for mild to moderate AD, providing rapid itch relief and reducing inflammation. ​JAK inhibitors carry a black box warning for serious risks such as infections, malignancies, and cardiovascular events due to potential systemic inhibition.12 Application of ruxolitinib should not exceed 60 g per week, and the treatment area should not be more than 20% body surface area to decrease the risk of systemic absorption. However, early long-term safety studies in patients using twice-daily ruxolitinib cream did not result in increased adverse events associated with systemic JAK inhibition.12,15 FDA approval for ruxolitinib cream in patients aged 2 to 11 years with mild to moderate AD was based on the TRuE-AD3 phase 3 trial (NCT04921969; N = 330) that enrolled children with body surface area involvement of 3% to 20%.16 Patients were randomly assigned to 1 of 3 treatment groups: 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or placebo twice daily for 8 weeks. After 8 weeks, Investigator Global Assessment treatment success was achieved by 36.6% of patients treated with 0.75% ruxolitinib cream and 56.5% of those treated with 1.5% ruxolitinib cream vs 10.8% with placebo (P ≤ .0001). Similar treatment effects were observed in Eczema Area and Severity Index (51.5% and 67.2% for 0.75% and 1.5% ruxolitinib cream, respectively, vs 15.4% for placebo; both P < .0001). The most common treatment-emergent adverse events (TEAEs) were upper respiratory tract infections and nasopharyngitis. Most TEAEs were mild or moderate and resolved without treatment interruption or discontinuation. No TEAEs suggestive of systemic JAK inhibition were observed.16 New and upcoming treatments include tapinarof, a therapeutic aryl hydrocarbon receptor modulating agent that decreases skin inflammation. The 1% tapinarof cream was initially approved in May 2022 for patients with plaque psoriasis, with multiple clinical trials for the use in extensive, moderate to severe AD ongoing or recently completed.12

Communication with and education of families are critical to ensuring safe and effective use of these newer treatments. Clinicians need to translate clinical data into understandable risks and benefits for parents and patients, often drawing from personal experience as parents themselves to build trust. In addition, clinicians must continuously evaluate when to escalate from topical therapies to phototherapy or systemic treatments, balancing efficacy with individual, patient-specific factors and preferences.

Stakeholder Insights

“To me, communication is everything,” Spizuoco said. “It’s always nice to have handouts or, if you can, do some demonstrations. Talking about first starting with just basic skin care, using moisturizers, gentle soaps, [and] lukewarm water, [then] pat dry—don’t rub dry. Try [to] demonstrate for the parents so they can see what you’re doing. And if there are kids who are old enough, like maybe 2 [years] and older, who can get a visual…show them how to do it, as well.”

“I think topicals play a role for every patient,” Hetzel said. “With the chronicity of the disease, maybe we want to get control in a short term and use something where we’re just plowing it down so they’re not so itchy, they can sleep, and everybody in the family can sleep, as well.… Can we give them something that’s going to give them more time in between those flares, that’s going to be more effective? [And] the newer nonsteroidal options that we have are so effective now and have more effective data in terms of itch control than even some of our tried-and-true topical steroids.… Atopic dermatitis is such a fickle disease. Even if you have them controlled, there’s still that little flare, or they have an allergy to something, and it just blows up like crazy.”

“For most patients [who] have persistent eczema, the utilization of a topical therapy generally—hopefully within 2 to 3 weeks—brings this flare state under control, and then the utilization of what we might call a maintenance therapy treatment…similar to asthma,” Oza said. “[Topical steroids] are not intended for chronic, daily, ongoing use. And eczema, for many people, is often persistent in certain areas of their body all the time.… That’s where…nonsteroidals [often] come in.” He added, “More and more recent data [have] come out with some of these therapies, [and] not only does the skin get better when you use it, but if you stop it, the time to your next flare compared [with] a steroid is much more prolonged. Clinical trials show that with topicals, 50% of patients can achieve these end points, which is pretty great. They allow a patient to potentially safely stay on a medication for a period of time.

“The black box warning for JAK inhibitors really stemmed from a large study looking at the original medication, called tofacitinib, [focusing] largely on…patients 60 [years] and [older] with many other health-related conditions,” Oza added. “Comparing it [with] other immunomodulators, [we’re] seeing these signatures for potential increased risk of clots…lymphoma, [and] squamous cell carcinoma…. So oral JAK inhibitors have a safety feature, and those are definitely things we counsel and talk to patients on.”

“I’m a big fan of the JAK inhibitors, orally and topically,” Spizuoco said. “The TRuE-AD3 trial shows that the 1.5% formulation is effective in pediatric patients—something else that we can arm our patients with, in addition to the other topical steroids that we have and…the other nonsteroidal anti-inflammatory creams. What I also find about this drug—roflumilast and the other nonsteroidal anti-inflammatory medications that we use topically—[is that] there really is no end limit. With topical steroids, we counsel our patients twice a day for 2 weeks and stop, and we put a firm stop on that. With these medications, I feel like we have a lot more leeway where we can say, for example, ‘Just use it on the weekends, and it will maintain your eczema flares from coming back.’”

Spizuoco added that although it is amazing that practitioners have these drugs approved, it does not necessarily mean they are going to go directly to the patient from the prescription pad. “I think that’s why there is such a trend toward topical steroids, particularly like a triamcinolone, [which is probably] the most prescribed topical steroid.… You get it for pennies. It’s just so easy to get.” She also emphasized the need for patient education: “Always [start] with our basic skin care, talking about the skin barrier balance…any potential triggers and trying to avoid them…bathing techniques, lukewarm water, gentle soaps, [and] things that are pH balanced. Just start with very basics. And then knowing our patients—try to categorize them as mild, moderate, or severe.… We have to start with the basics and then try [to] figure out which medication is going to fit into their lifestyle, which is appropriate for their age, for their disease severity, [and] their locations, and then really working with getting them approved…. Access is such a key thing for our patients.”

“I think the TRuE-AD study is so great,” Hetzel agreed. “Ultimately, I use my maternal instinct and try to translate it as what I would want to know…and I think that has broken me through a lot more barriers…and I think they appreciate that, too. I also have them follow-up as well. I think that’s important, too. We have availability, where I am more confident and comfortable to say, ‘Come back to me in 4 weeks [or] 8 weeks. Let me see how you’re doing.’”

“I think [with] all our topicals, even the ones that are nonsteroids, we are hoping to be able to use them on a daily basis and then get to a state where they can just do less of it, and that’s the model,” Oza said. “We often talk about [doing] it on the weekend to prevent it during the school week, so that’s a goal target for many patients who have mild to moderate persistent eczema.… You want to feel like you’re moving in the right direction by being able to take breaks from it. And if you really can’t, it probably signifies that maybe you don’t have mild to moderate eczema, and maybe you have moderate to severe eczema…and we often move from topicals to systemics when we feel like we can’t capture the control.”

“I think we all have different experiences; we’re all trained differently,” Spizuoco said. “None of our guidelines say you have to start with this exact nontopical. We have a buffet of all these different things, [and] we are left…using our own clinical judgment [and] the patient’s past experiences to arrive at decisions for families. Quality of life is so important [in] atopic dermatitis,” she said. “It’s one of these conditions that not only [are]…visual, but [also very] symptomatic. So that’s what we need to work on as far as treatment success with our patients, not only the appearance of their skin lesions but also how their symptoms are—their itch, then back to their quality of life. Are they sleeping at night? Are they able to go and ace their exam or win their basketball game the next day? Or are [parents] staying up all night with their kids because they’re scratching? [So they apply] their medications [and] now didn’t meet their deadline at work because they’re exhausted, and they’re working through their lunch break to get things done. There are so many different factors for treatment success with our [patients with] atopic dermatitis using topical medications.”

Real-World Evidence in the Use of Topical Agents in Pediatric AD

Evaluation of treatment patterns in real-world studies can help optimize care for patients with AD in diverse settings.17 A real-world study in pediatric patients based on a US database from commercial insurance and Medicaid administrative claims data (January 2011-December 2016; N = 607,258) concluded that there is no consensus on a uniform approach to disease management despite high prevalence and disease burden of pediatric AD in the United States.10 Results from this claims data analysis indicated that most patients were not seen by a specialist. Moreover, treatment varied greatly by provider type, with specialists more likely to treat with higher-potency topicals and/or systemics.10 Overall, 86.7% were prescribed topical treatments—predominantly corticosteroids (85.9%)—whereas 5.4% were prescribed calcineurin inhibitors.10 More recent data from TARGET-DERM (NCT03661866), a longitudinal, observational study of adult and pediatric patients with AD (N = 1263, of whom 549 [43%] are children), suggest the proportion of participants using topical steroids has reduced over time, potentially due to the increased approval and availability of nonsteroidal treatments in younger age groups.17

A US claims database (Optum Research Database) study investigated the effects of ruxolitinib cream use in patients 12 years and older with AD who had continuous enrollment in a commercial or managed Medicare plan during the 6‑month baseline period prior to the index date (first claim for ruxolitinib cream) and the 12‑month follow‑up period.18 Over the 12 months of follow-up, there was 50% reduction in the use of topical corticosteroids, along with reductions in other topical therapies and oral corticosteroids. More than 90% of biologic-naive patients avoided biologics in the 12 months following ruxolitinib cream initiation.18 This and findings from a 6‑month study support the idea that ruxolitinib cream may reduce the need of other topical therapies, oral corticosteroids, and biologics in patients with AD.18,19

Patient-reported outcome (PRO) measures play a key role in assessing treatment efficacy in AD. The INTEGUMENT-I (NCT04773587) and INTEGUMENT-II (NCT04773600) phase 3 trials of roflumilast cream (0.15%) in patients 6 years and older with AD used the patient-reported Worst Itch Numerical Rating Scale (WI-NRS).13 Improvement in itch is crucial, as it is the most common and burdensome symptom of AD and negatively impacts the patient’s quality of life. Statistically significantly more patients treated with roflumilast cream with baseline WI-NRS of 4 or more achieved at least a 4-point reduction at weeks 1, 2, and 4 in both trials, compared with patients treated with vehicle cream. Notably, itch improved with roflumilast treatment as compared with vehicle treatment at 24 hours after the first application.13

Stakeholder Insights

Oza said that it’s important to also pay attention to those PROs when assessing a patient. “Because we also have data that [portray] those other outcomes…[the patient’s] skin at that one visit [may not compare] one to one with the quality-of-life outcome measures that are often done in these studies. So, as a doctor, when we’re trying to define success, we’re integrating what we see at that snapshot of time in our office of how bad their eczema looks, but we’re also trying to capture what their experience [has] been with their eczema since our last visit. And we integrate both when deciding on therapy selection.” He said he uses PROs in his practice to evaluate patients’ quality of life while on treatment.

“The reality of health care in the US is that even though something is approved doesn’t mean your patient has access to it,” Oza said. “I experience that because I work at 2 primary sites. I work at our NYU hospital, where most of the patients in my practice are commercially insured. Then 2 other days out of the week, I work at Bellevue Hospital, which is our safety-net hospital for New York City, [and] 95% of those patients are on a managed Medicaid plan, which has a very restrictive formulary list.… It can be frustrating [when] you feel like [you found] the best therapy for [your] patient but [you] can’t really access it.”

He explained that he does not think that a patient who has never been on a topical steroid should immediately start on one of the newer therapies. “They are more expensive. But most people’s lived experience with eczema is they have often trialed many different things. And it seems very appropriate at that point in time, if they’re in this mild to moderate zone, that we have the ability to try something that has pretty good safety—excellent safety data, actually—and pretty good efficacy data.”

Spizuoco said, “With ruxolitinib, roflumilast, [and] tapinarof—those are the 3 I use—I found it’s definitely delaying me [from] jumping to a biologic or a more systemic medication for my patients. That being said, these topicals are more for mild to moderate patients. Our systemics are more for moderate to severe [cases]. But…what’s the definition between mild, moderate, [and] severe? It’s not just based on what the FDA tells us or what a clinical trial will tell us. We always have to factor in—and we all do—quality-of-life measures with our patients.”

“We are working in a time where we have a toolbox that used to be empty, but now this toolbox is becoming more and more full,” Oza said. “We don’t have a lot of head-to-head data to compare these treatments, so we’re trying to use our own clinical judgment when we’re sitting in the room with the patient, [as well as] our own past experiences, to help decide next steps.… What can I do better for my patients? How can I get them the skin that they want, [and] the skin that they feel comfortable and confident with, no matter what disease state?” •

References

1. Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. Lancet. 2020;396(10247):345-360. doi:10.1016/s0140-6736(20)31286-1

2. Odhiambo JA, Williams HC, Clayton TO, Robertson CF, Asher MI; Isaac Phase Three Study Group. Global variations in prevalence of eczema symptoms in children from ISAAC phase three. J Allergy Clin Immunol. 2009;124(6):1251-8.e23. doi:10.1016/j.jaci.2009.10.009

3. Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and other health and demographic factors: a US population-based study. J Allergy Clin Immunol. 2013;132(5):1132-1138. doi:10.1016/j.jaci.2013.08.031

4. Abuabara K, Ye M, Margolis DJ, et al. Patterns of atopic eczema disease activity from birth through midlife in 2 British birth cohorts. JAMA Dermatol. 2021;157(10):1191-1199. doi:10.1001/jamadermatol.2021.2489

5. Tian J, Zhang D, Yang Y, et al. Global epidemiology of atopic dermatitis: a comprehensive systematic analysis and modelling study. Br J Dermatol. 2023;190(1):55-61. doi:10.1093/bjd/ljad339

6. Simpson EL, Bieber T, Eckert L, et al. Patient burden of moderate to severe atopic dermatitis (AD): insights from a phase 2b clinical trial of dupilumab in adults. J Am Acad Dermatol. 2016;74(3):491-498. doi:10.1016/j.jaad.2015.10.043

7. Langan SM, Silcocks P, Williams HC. What causes flares of eczema in children? Br J Dermatol. 2009;161(3):640-646. doi:10.1111/j.1365-2133.2009.09320.x

8. AAAAI/ACAAI JTF Atopic Dermatitis Guideline Panel; Chu DK, Schneider L, Asiniwasis RN, et al. Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE- and Institute of Medicine-based recommendations. Ann Allergy Asthma Immunol. 2024;132(3):274-312. doi:10.1016/j.anai.2023.11.009

9. Amerio P, Ferrucci SM, Galluzzo M, et al. A multidisciplinary approach is beneficial in atopic dermatitis. Dermatol Ther (Heidelb). 2024;14(6):1443-1455. doi:10.1007/s13555-024-01185-1

10. Paller AS, Siegfried EC, Vekeman F, et al. Treatment patterns of pediatric patients with atopic dermatitis: a claims data analysis. J Am Acad Dermatol. 2020;82(3):651-660. doi:10.1016/j.jaad.2019.07.105

11. Farmer WS, Marathe KS. Atopic dermatitis: managing the itch. In: Feldman SR, Strowd LC, Lovell KK, eds. Management of Atopic Dermatitis: Methods and Challenges. Springer International Publishing; 2024:191-207.

12. Lovell K, Ackerson B, Thorpe R, Nicholas M. Topical prescription management. In: Feldman SR, Strowd LC, Lovell KK, eds. Management of Atopic Dermatitis: Methods and Challenges. Springer International Publishing; 2024:117-129.

13. Simpson EL, Eichenfield LF, Alonso-Llamazares J, et al. Roflumilast cream, 0.15%, for atopic dermatitis in adults and children: INTEGUMENT-1 and INTEGUMENT-2 randomized clinical trials. JAMA Dermatol. 2024;160(11):1161-1170. doi:10.1001/jamadermatol.2024.3121

14. Incyte announces additional FDA approval of Opzelura (ruxolitinib) cream in children ages 2-11 with atopic dermatitis. News release. Businesswire. September 18, 2025. Accessed October 27, 2025. https://www.businesswire.com/news/home/20250918551027/en/Incyte-Announces-Additional-FDA-Approval-of-Opzelura-Ruxolitinib-Cream-in-Children-Ages-2-11-with-Atopic-Dermatitis

15. Papp K, Szepietowski JC, Kircik L, et al. Long-term safety and disease control with ruxolitinib cream in atopic dermatitis: results from two phase 3 studies. J Am Acad Dermatol. 2023;88(5):1008-1016. doi:10.1016/j.jaad.2022.09.060

16. Eichenfield LF, Stein Gold LF, Simpson EL, et al. Efficacy and safety of ruxolitinib cream in children aged 2 to 11 years with atopic dermatitis: results from TRuE-AD3, a phase 3, randomized double-blind study. J Am Acad Dermatol. 2025;93(3):689-698. doi:10.1016/j.jaad.2025.05.1385

17. Abuabara K, Eichenfield LF, Bissonnette R, et al. Real-world evidence on atopic dermatitis: baseline characteristics and predictors of treatment choice in the TARGET cohort. J Am Acad Dermatol. 2023;89(2):345-347. doi:10.1016/j.jaad.2022.08.065

18. Liu J, Desai K, Teng CC, et al. Association of ruxolitinib cream initiation with continued reduction in use of other topical treatments, oral corticosteroids, and biologics for atopic dermatitis. Presented at: Fall Clinical Dermatology Conference; October 24-27, 2024; Las Vegas, NV.

19. Liu J, Desai K, Teng CC, et al. Atopic dermatitis treatments before and after initiation of ruxolitinib cream: 6-month follow-up analysis of a us payer claims database. Clinicoecon Outcomes Res. 2025;17:69-77. doi:10.2147/ceor.S506043