The Shifting Landscape of Atopic Dermatitis Treatments

BRAD P. GLICK, DO, MPH, FAAD
Member, AAD Board of Directors
Dermatology Residency Director
Larkin Health System PI, GSI Clinical Research
ASDS Advocacy Ambassador
Miami, Florida

MHE: What are the main challenges in managing atopic dermatitis (AD)?

Glick: Managing AD presents several challenges that primarily are influenced by the patient’s age. We see patients from the neonatal period through adulthood requiring age-appropriate strategies and communication especially when the parents for younger patients are involved.

A key challenge is preserving the skin barrier. I emphasize barrier restoration for all patients. Effective communication is crucial to provide clear education and personalized plans; this is often supported by preprinted sheets tailored to each patient.

Assessing disease extent and severity is another challenge. Mild cases might be managed with topical therapy, whereas moderate cases may need a combination of therapies along with barrier restoration. Environmental exposures also play a considerable role, and triggers may need to be removed to prevent flares. In addition, it is vital to address other flare factors (e.g., secondary infections caused by Staphylococcus aureus) to ensure comprehensive management.

MHE: What are the key considerations for treatment?

Glick: In today’s treatment landscape, we have more options beyond topical corticosteroids (TCS); these include topical calcineurin inhibitors (TCIs) and PDE4 inhibitors. Despite these advancements, corticosteroids remain a mainstay of initial therapy. However, they present challenges such as tachyphylaxis and require intermittent therapy—typically two weeks on, one week off—to mitigate this risk.

Corticosteroids also pose risks like increased transepidermal water loss, facial acne and steroid-induced folliculitis; it also may cause dyspigmentation, particularly in patients with darker skin tones. These side effects necessitate careful management and cycling with other therapies like calcineurin inhibitors.

Combining corticosteroids with newer nonsteroidal treatments is now more accepted, and it offers a paradigm shift in treatment strategies. However, this also increases the cost burden for patients and the healthcare system. The challenge lies in providing effective treatment while minimizing side effects and managing costs.

MHE: What are some of the differences in efficacy, safety and cost-effectiveness among the topical therapies for AD management?

Glick: Efficacy, safety and cost-effectiveness are key considerations when comparing topical therapies for AD. Twenty-five years ago, the discussion would have centered on corticosteroids alone, but now we have multiple options including TCIs, the newer topical JAK inhibitor ruxolitinib and PDE4 inhibitors like crisaborole and roflumilast.

Corticosteroids are highly effective and widely used. They work quickly, but they are unsuitable for long-term use due to risks like tachyphylaxis, skin atrophy and other side effects. They are cost-effective if covered by insurance, but they require cycling with other therapies to minimize side effects.

TCIs are effective for long-term use, and they can be applied from the face to the toes. However, they can cause local irritation as their prescribing information carries a boxed warning. TCIs are generally more expensive than are other medications, and they may not be covered by all health plans, which makes them less cost-effective. They work well, but they are often used in combination with corticosteroids.

Ruxolitinib is a novel and revolutionary topical JAK inhibitor that is highly effective and safe for use on all body areas including the face. It has produced substantial improvement in clinical trials, but it comes with a high cost and a boxed warning despite its favorable safety profile. This makes it particularly useful for patients who require frequent corticosteroid cycling.

Crisaborole, approved in 2016, is moderately effective for managing mild to moderate AD. However, its use is often limited by stinging and burning. It remains expensive without a generic option, and it is still being explored for other uses.

Roflumilast, a recently approved PDE4 inhibitor, is used once daily. It has shown promise in treating plaque psoriasis and seborrheic dermatitis. Its cost and coverage are potential concerns, yet it offers another option for managing mild to moderate AD.

Overall, each therapy presents a balance of efficacy, safety and cost and requires careful consideration in treatment planning. The introduction of newer therapies provides more options but also increases the overall cost burden on patients and the healthcare system.

MHE: How do treatment strategies and considerations differ for pediatric patients compared to adult patients?

Glick: The key consideration for pediatric patients with AD is to avoid aggressive treatment whenever possible. For children with mild to moderate AD, barrier restoration and minimal use of topical therapies (e.g., corticosteroids, other referenced treatments) are ideal. The treatment strategy varies based on disease severity—whether mild, moderate or severe.

Children often present with itchiness that they may not verbally express but that they demonstrate through constant scratching, which leads to sleep disturbances for both their parents and them. Effective management focuses on reducing itch, maintaining barrier function, avoiding irritants and treating local infections if present. For moderate cases, more aggressive topical therapies may be necessary. For example, use of ruxolitinib cream has age limitations, whereas treatment TCIs can be used from the age of 3 months. Corticosteroids, although widely used, require careful consideration of potency and duration, especially for younger patients with smaller body surface areas.

In cases of moderate to severe AD in children, short-term use of higher potency corticosteroids may be necessary to control inflammation, and systemic therapies like methotrexate or cyclosporine must be avoided unless absolutely required. The goal is to select the therapy that offers the greatest efficacy and safety based on the child’s age and disease severity.

For severe cases, biologic therapy with dupilumab, now approved for children as young as 6 months of age, provides a valuable option. This approach aligns with the American Academy of Dermatology’s guidelines and emphasizes barrier restoration, severity assessment and appropriate therapy selection based on patient age and disease severity.¹

MHE: Regarding the use of multiple topical therapies, how should they be used, and what is your approach to sequencing topical treatments before moving to systemic options?

Glick: I start by repairing the skin barrier. Corticosteroids are an appropriate initial therapy, but I increasingly use newer nonsteroidal agents (e.g., ruxolitinib cream, 1.5%) that can be applied twice daily for eight weeks and then intermittently. When patients do not respond to intermittent corticosteroid cycles, I switch therapies.

Corticosteroids remain a cornerstone of therapy, especially for children, adolescents and adults. However, if the cost of newer nonsteroidal therapies decreases and access to older TCIs improves, these agents can be used more for maintenance. My approach involves starting with barrier maintenance, using burst therapy with corticosteroids and then transitioning to nonsteroidal maintenance five to seven days a week based on the inflammatory burden and itch severity.

Itch is a critical factor in managing AD. We measure it using a numeric rating scale from zero to 10, tracking changes over time. This method, similar to those used in clinical trials, helps to guide therapeutic decisions and facilitates shared decision-making with patients and their families.

MHE: What factors do you consider when you want to transition a patient from topical therapy?

Glick: When a patient transitions from mild to moderate disease with increasing body surface area involvement and worsening itch, it is time to consider systemic therapy. For example, if a patient’s itch worsens despite the use of TCS, moisturizers and additional treatments like TCIs or JAK inhibitors, topical therapies may no longer be sufficient.

We also consider the impact on the patient’s quality of life (QOL). If the itch-scratch cycle is out of control and it leads to excoriations, lack of sleep and significant disruptions to daily life or school attendance for children, it is clear the disease burden is high. When the comprehensive care plan including barrier management and possibly adjunct therapies like bleach baths fails to control the symptoms, it is time to step back and consider systemic therapy. This holistic view of the patient’s condition and QOL helps determine the need for transitioning to more aggressive treatment options.

MHE: What are some challenges with systemic therapies, and why is it important to maintain patients on therapy in general as long as we can?

Glick: In managing AD, the primary objective is to reduce itch to minimal levels, ideally achieving what we refer to as zero-one—almost no itch. This improvement significantly impacts patients’ QOL by allowing better sleep and reducing overall disease burden. When the affected body surface area exceeds 10% to 20%, the disease becomes more severe, necessitating aggressive treatment.

For maintaining the skin barrier and reducing inflammation, topical therapies are often preferred. Phototherapy, though underused, can be effective in some cases. However, with the advent of newer systemic therapies, particularly biologics and JAK inhibitors, we now have additional options to reduce itch and inflammation rapidly. JAK inhibitors can alleviate symptoms within days, and topical therapies like ruxolitinib have produced improvements in as early as 15 minutes to a day.

The goals of both topical and systemic therapies are to control itch, preserve the skin barrier and reduce the inflammatory burden. Clinical trials have demonstrated that patients in placebo groups often experience more infections due to compromised skin barriers. Thus, it is crucial to manage patients effectively to prevent such complications.

Despite the preference for topical therapies, the availability of effective systemic treatments provides a significant advantage for patients with more severe or refractory AD. When multiple topical therapies fail to control the disease, systemic options may be considered to achieve better management and to improve patient outcomes.

MHE: How can strategies be evaluated or implemented to prolong the effectiveness of topicals and other nonsystemic treatments?

Glick: To prolong the effectiveness of topicals and other nonsystemic treatments for AD, barrier restoration is crucial. This involves adhering to basic principles such as using gentle cleansers and avoiding emulsifying soaps that strip the skin barrier. Effective management starts with maintaining the skin barrier through proper cleansing and regular moisturizing.

Patient education is essential. Adults, adolescents and parents of young children with AD must understand the importance of adherence to therapy. This includes following written treatment plans, which can be preprinted or personalized to address individual needs and common triggers.

Cycling therapies and incorporating phototherapy can also help to manage the disease effectively and to reduce the need for systemic treatments. By keeping the disease burden low through these strategies, we can limit the number of therapies required, potentially avoiding the transition to systemic treatments.

Lastly, it’s important to recognize the heterogeneous nature of AD. Unlike other inflammatory skin diseases like psoriasis, AD can flare up quickly due to various triggers such as food or environmental exposures. Continuous monitoring and timely adjustments in treatment plans are necessary to manage these sudden changes.

MHE: How can treatment approaches, associated costs and patient burden among various AD management options be assessed and compared to inform formulary decisions and care pathways?

Glick: To assess and compare treatment approaches, associated costs and patient burden among various AD management options, managed care organizations and payers should consider several key factors. Focusing on barrier restoration can significantly reduce the need for prescriptions. Preserving the skin barrier, improving cracks and decreasing portals of entry can reduce inflammatory burden and improve patient outcomes.

Using effective topical therapies that do not involve corticosteroids but that work as well as low- to mid-potency corticosteroids can also limit the burden on managed care plans. As a clinician, my primary concern is improving my patient’s condition, but it is also important to consider how treatment decisions impact healthcare costs.

Identifying and removing triggers such as local irritants is crucial. Patch testing, which is often underused, can help to pinpoint specific triggers and prevent disease flares. Managing the barrier and treating with antibiotics when there is clinical or culture-proven S. aureus infection can prevent escalation to more costly therapies.

In summary, by emphasizing barrier restoration, identifying and removing triggers and using effective topical treatments other than TCS, we can manage AD more cost-effectively. This approach reduces the need for aggressive therapies and ultimately lowers the financial burden on payers while improving patient outcomes.

MHE: What is the potential economic impact of incorporating these new therapies that have been coming to market recently (e.g., two weeks ago versus a couple of years ago) into formularies, and how can their use be optimized effectively?

Glick: Incorporating new therapies into formularies has significant economic implications. Newer-generation therapies often come with impressive data but also at a premium cost. It is crucial to be mindful of these costs, especially for patients with limited disease. Initial treatments should focus on managing the condition from the outside, avoiding triggers and using cost-effective therapeutics.

The severity of the disease plays a significant role in treatment decisions. For patients with extensive disease, severe symptoms and a high impact on QOL, more potent therapies may be necessary. However, starting with simple interventions and ensuring adherence to treatment regimens and with care plans can often lead to successful outcomes without resorting to highly expensive treatments.

Effective optimization involves a balanced approach. Aggressiveness in treatment doesn’t mean immediately opting for the most potent therapies but, rather, being organized and having a structured care plan. This approach can help manage costs while still achieving positive patient outcomes.

MHE: How should AD-related QOL improvements be evaluated and compared across different treatment options?

Glick: Evaluating and comparing AD-related QOL improvements across different treatment options should focus on patient-reported outcomes (PROs). The 21st Century Cures Act aimed to make clinical trials more patient-oriented and highlighted the importance of PROs like itch, which is a major concern for AD patients. Tools such as the Dermatology Life Quality Index and other QOL measures assess the impact on daily activities, sleep and overall well-being.

Managed care organizations should consider these PROs when approving therapies. It’s crucial for clinicians to document the severity of itch and its impact on QOL (e.g., sleep disruption, limitations in daily activities). For example, patients may report only sleeping two or three hours each night due to scratching, which significantly affects their QOL.

John Silverberg’s 2022 paper in Dermatitis underscores that itch is a primary concern for patients and is frequently measured in clinical trials.² Managed care plans need to see this documented evidence of how inflammatory burden and itch impact patients’ lives, including the ability to work and the risk of accidents.

AD is complex, and QOL measures are vital for comprehensive treatment evaluation. Clinicians must diligently document these aspects to inform managed care decisions and ensure that patient well-being is prioritized in therapeutic approvals.

MHE: How do the 2024 American Academy of Dermatology (AAD) guidelines for AD treatment align with current managed care strategies, and what adjustments might be necessary in future guidelines?¹

Glick: The 2024 AAD guidelines for AD align with managed care strategies in several ways, but there are areas that need adjustment. There are three main guideline categories: comorbidities, topical therapies and systemic therapies. Comorbidities play a role in therapeutic selection although less so than in diseases like psoriasis. Understanding the comorbidities associated with AD is crucial, as the comorbidities influence treatment decisions.

From a topical therapy standpoint, the guidelines include TCS, TCIs and PDE4 inhibitors. Recently, topical ruxolitinib cream was added, and managed care plans should consider this treatment for its potential role in treating AD.

For systemic therapies, traditional options like methotrexate, azathioprine and cyclosporine are typically used for severe cases. However, the advent of biologics and JAK inhibitors has shown substantial responses in clinical trials with improved safety profiles. This shift is supported by recent literature, including Michael Cameron’s op-ed in The Dermatologist and Chris Bunick’s article in the Journal of Drugs in Dermatology, which highlight the favorable safety profiles of newer therapies compared to older ones.^3,4

Managed care strategies must balance the costs and benefits of these therapies. While newer biologics and JAK inhibitors are expensive, their side effect profiles are more favorable, making them a viable option for patients with moderate to severe disease. Clinicians should focus on thorough documentation to secure approval for these advanced therapies.

The primary challenge is managing costs while providing effective treatment. Starting with cost-effective, mid-range topicals and ensuring comprehensive barrier management can delay the need for systemic therapies. However, for patients with significant inflammatory burdens, newer-generation therapies should be considered despite their cost, as they offer substantial improvements in QOL.

In summary, the AAD guidelines align with many current managed care strategies, but future adjustments should emphasize the balance between cost-effectiveness and the benefits of newer therapies. This approach ensures optimal patient outcomes while managing healthcare expenditures.

REFERENCES

1. Davis DMR, Drucker AM, Alikhan A, et al. Guidelines of care for the manage­ment of atopic dermatitis in adults with phototherapy and systemic therapies. J Am Acad Dermatol. 2024;90(2):e43-e56. doi:10.1016/j.jaad.2023.08.102

2. Silverberg JI, Chiesa-Fuxench Z, Margolis D, et al. Epidemiology and burden of sleep disturbances in atopic dermatitis in US adults. Dermatitis. 2022;33(6S):S104-S113. doi:10.1097/DER.0000000000000731

3. Cameron M. JAK inhibitor safety: what did ORAL Surveillance really teach us? The Dermatologist. March 2023. Accessed August 21, 2024. https://www.hmpgloballearningnetwork.com/site/thederm/cover-story/jak-inhibitor-safety-what-did-oral-surveillance-really-teach-us

4. Daniele S, Bunick C. JAK inhibitor safety compared to traditional systemic immunosuppressive therapies. J Drugs Dermatol. 2022;21(12):1298-1303. doi:10.36849/JDD.7187