From Disease Assessment to Advanced Therapy: A Practical Framework for Atopic Dermatitis

From Disease Assessment to Advanced Therapy: A Practical Framework for Atopic Dermatitis

This supplement reviews the assessment and management of moderate to severe atopic dermatitis (AD), with a focus on guideline-aligned treatment selection. Expert faculty examine practical approaches to evaluating disease severity, escalating therapy, and integrating newer AD therapies into clinical practice while addressing common barriers to care and considerations for safe, evidence-based management. The supplement also incorporates the patient perspective, providing insights into the lived experience of AD and how treatment decisions affect disease burden and quality of life. Together, these perspectives provide clinicians with practical guidance to support individualized treatment decisions for patients with moderate to severe AD.

Introduction
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczematous lesions, xerosis, and persistent pruritus.¹ It results from a complex interaction between epidermal barrier dysfunction, immune dysregulation, genetic susceptibility, and environmental factors.¹ Although AD commonly begins in childhood, it may persist into adulthood or develop later in life. Skin pain, recurrent infections, and comorbid atopic conditions may further complicate the disease course.¹ At the population level, AD is a leading cause of nonfatal disease burden and accounts for the highest disability-adjusted life-year burden among skin diseases.²

Beyond its visible manifestations, AD can disrupt sleep, concentration, and daytime functioning, primarily because of persistent pruritus and the resulting itch–scratch cycle.³ In the 28-country MEASURE-AD study, at least 55% of patients with moderate to severe AD reported moderate to severe pruritus. The mean Dermatology Life Quality Index score was 10.8, indicating a very large effect on patients’ lives.³ Sleep disruption can contribute to fatigue and impaired performance at school or work, further increasing the functional burden of the disease.

The visible and unpredictable nature of AD may contribute to embarrassment, social withdrawal, strained relationships, and limitations in daily and intimate activities. Its association with depression across age groups supports routine assessment of psychological health.⁴ Caregivers may also experience sleep disruption, emotional distress, exhaustion, and increased household costs.⁵ Daily skin care, topical treatment, medical visits, costs, and concerns about efficacy or safety add to the burden and may reduce adherence. More severe AD is associated with greater work impairment, healthcare use, and treatment dissatisfaction.⁶ Assessment therefore includes skin involvement and severity together with itch, sleep, psychosocial health, daily functioning, treatment demands, and patient and caregiver goals.

This supplement extends the Push Past in AD: Treatment Escalation in Moderate to Severe Atopic Dermatitis Impact Live meeting series. Insights from physician assistant Kristine Kucera and patient advocate Chava Bayla Wald are incorporated to connect current evidence with the clinical and patient considerations that influence assessment, treatment escalation, and shared decision-making.

Recognizing Inadequately Controlled Disease
Assessment of the impact of AD on daily life includes disease severity and disease control.⁷ Disease severity characterizes the intensity and extent of AD at a specific time point, whereas disease control describes how well symptoms and their effects on daily life are managed over time.⁷ Persistent itch, sleep disruption, frequent flares, or involvement of sensitive or highly visible areas of skin may indicate poor control even when visible disease is limited.⁸ Clinical findings should therefore be considered together with the patient’s experience and treatment history.

Validated assessment tools help integrate these components of disease assessment and provide a consistent method for monitoring treatment response.⁹ The Eczema Area and Severity Index (EASI) assesses the extent and intensity of clinical signs across 4 body regions but does not capture itch, sleep, or quality of life.¹⁰ The validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) provides a simpler global rating, while body surface area (BSA) measures disease extent.¹¹ For routine practice, the Harmonising Outcome Measures for Eczema (HOME) Clinical Practice initiative recommends EASI, vIGA with BSA, or IGA×BSA.⁹

To complement these clinician-assessed measures, patient-reported outcome measures (PROMs) capture symptoms and effects not apparent during examination. The Patient-Oriented Eczema Measure (POEM) assesses 7 symptoms over the preceding week, while numeric rating scales quantify itch.¹² The Dermatology Life Quality Index (DLQI) and its age-specific versions evaluate effects on daily life.¹² The brief, HOME-recommended Atopic Dermatitis Control Tool (ADCT) and Recap of Atopic Eczema (RECAP) assess patient-perceived control and correlate strongly, supporting the use of either instrument in routine practice.^7,13 Figure 1 summarizes complementary clinician-assessed and patient-reported tools for evaluating clinical signs, disease extent, symptoms, control, and effects on daily life.

Figure 1. Validated Assessment Tools and Patient-Reported Outcomes for Evaluating Atopic Dermatitis

The 4 categories represent complementary components of assessment rather than a required sequence. 
AD, atopic dermatitis; ADCT, Atopic Dermatitis Control Tool; BSA, body surface area; CDLQI, Children’s Dermatology Life Quality Index; DLQI, Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; HOME, Harmonising Outcome Measures for Eczema; IDQoL, Infants’ Dermatitis Quality of Life Index; IGA, Investigator’s Global Assessment; NRS, Numeric Rating Scale; POEM, Patient-Oriented Eczema Measure; RECAP, Recap of Atopic Eczema; vIGA-AD, Validated Investigator Global Assessment for Atopic Dermatitis.
Developed from references.^{7, 9-12}

Together, these assessments inform treatment goals based on the features causing the greatest burden, including itch, sleep loss, pain, visible lesions, and interference with work or social activities. Treat-to-target recommendations propose assessment at approximately 3 months and evaluation of an optimal target at 6 months, with systemic treatment decisions based on the Patient Global Assessment, improvement in at least 1 disease domain, and treatment safety and tolerability.¹⁴ The AHEAD recommendations further incorporate patient-identified disease features and define moderate and optimal targets, with optimal targets representing minimal disease activity.⁸

When Treatment Escalation Is Appropriate
Persistent lesions, itch, sleep disruption, impaired functioning, frequent flares, or sensitive-site involvement may indicate inadequate control despite limited BSA or an apparent response.^8,15 Additionally, a partial response remains insufficient when meaningful disease burden persists. Before escalation, clinicians should review patient-centered goals, diagnosis, infection or allergic contact dermatitis, treatment potency and duration, application technique, and adherence.^8,15 Addressing regimen complexity, corticosteroid concerns, vehicle preference, cost, and inconsistent guidance can help distinguish inadequate treatment exposure from pharmacologic failure.¹⁶

After these factors are addressed, treatment response is reassessed across clinical and patient-reported domains. Improvement in the Patient Global Assessment and at least 1 disease domain supports continuation, whereas failure to achieve either target favors a change in systemic therapy.¹⁴ An incomplete or lost response prompts renewed evaluation of the diagnosis, adherence, topical therapy, infection, and new exposures before systemic treatment is considered ineffective.¹⁷

Source: Push Past in AD Impact Live faculty–patient discussion featuring Kristine Kucera, PA-C, and patient ambassador Chava Wald, July 30, 2026. Unpublished program transcript.

Selecting Advanced Therapy
When reassessment confirms inadequate control despite optimized therapy, guidelines recommend approved biologics or oral Janus kinase (JAK) inhibitors for eligible adults; phototherapy and conventional immunosuppressants are conditional options, and routine systemic corticosteroid use is discouraged.^18,19 Treatment selection considers how quickly and to what extent disease control is needed, previous treatment response, monitoring requirements, access, and patient preferences. The benefit–risk assessment also incorporates age, smoking history, comorbidities, concomitant medications, pregnancy or lactation, and histories of infection or malignancy. Cardiovascular and thromboembolic risk, renal and hepatic function, and immunocompetence require particular attention when selecting an oral JAK inhibitor.^20,21

Currently available biologics inhibit distinct pathways involved in AD. Dupilumab blocks signaling through the interleukin (IL)-4 receptor alpha subunit, tralokinumab and lebrikizumab target IL-13, and nemolizumab inhibits signaling through the IL-31 receptor alpha subunit. All have demonstrated improvements in skin lesions and patient-reported symptoms, although differences in their mechanisms and clinical evidence may inform which agent best matches an individual patient’s clinical presentation. Network meta-analyses identify biologics among the systemic treatments with the most favorable overall safety profiles.²²

Oral JAK inhibitors block multiple cytokine pathways involved in inflammation and pruritus, contributing to their rapid effects. Upadacitinib 30 mg and abrocitinib 200 mg have produced among the highest short-term probabilities of skin clearance and itch improvement.²² At week 16, EASI 75 response rates with upadacitinib 30 mg were approximately 80% and 73% in Measure Up 1 and 2, respectively, versus 16% and 13% with placebo.²³ Head-to-head trials also demonstrated earlier itch improvement and higher early skin clearance responses than dupilumab (Table 1).^24-27 Rapid onset is particularly relevant for patients with severe itch, sleep disruption, or extensive disease.

Table 1. Comparative Evidence for Oral JAK Inhibitors Versus Dupilumab in Moderate to Severe AD

EASI 75/90/100, at least 75%/90%/100% improvement in Eczema Area and Severity Index; NRS, Numeric Rating Scale; PP-NRS4, at least a 4-point improvement in Peak Pruritus NRS; WP-NRS, Worst Pruritus NRS.

The rapid onset and high short-term response rates observed with some oral JAK inhibitor regimens must be balanced against their safety and monitoring requirements. Biologics may be favored when long-term safety or limited laboratory surveillance is needed, whereas oral JAK inhibitors offer rapid symptom relief, greater skin clearance, and oral administration for patients with acceptable baseline risks.²⁸ Long-term extension studies demonstrate sustained efficacy with biologics,^39-32 whereas integrated analyses provide longer-term safety data for abrocitinib and upadacitinib.^33,34 Route of administration, dosing frequency, adherence, storage, and potential drug interactions may also influence treatment selection.

Baseline testing includes blood counts, liver and renal function, lipids, tuberculosis and viral hepatitis screening, and vaccination review, including herpes zoster vaccination when indicated. Laboratory testing is generally repeated within 4 to 12 weeks and thereafter based on the agent used and clinical findings.^21,35 Although serious events have been uncommon in AD trials, class warnings support individualized risk assessment. Biologic-associated concerns include ocular symptoms, injection site reactions, and hypersensitivity.^19,26,27

Individualizing Treatment Through Shared Decision-Making
Individualizing treatment for AD involves translating clinical evidence into a plan that addresses the outcomes most important to the patient. Objective measures of skin involvement remain necessary but may not identify persistent itch, sleep disruption, pain, functional limitations, or treatment inconvenience. During the Impact Live discussion, physician assistant Kristine Kucera emphasized that clear or limited disease does not necessarily indicate adequate control. Asking what the patient is unable to do because of AD can reveal impacts on daily life that are not captured by BSA or lesion severity.^8,36

The patient’s perspective is particularly important when evaluating children and adolescents. Patient ambassador Chava Wald noted that caregivers may recognize scratching, bleeding, and sleep loss without being aware of embarrassment, anxiety, peer interactions, or activities the child has begun to avoid. Inviting younger patients to describe their experiences in age-appropriate language provides a more complete understanding of disease burden and helps identify meaningful treatment goals.

Preferences regarding efficacy, safety, route of administration, dosing frequency, monitoring, and speed of improvement vary among patients and cannot be inferred from disease severity alone.^36,37 Some patients prioritize rapid itch relief or extensive skin clearance, whereas others place greater importance on minimizing adverse effects or laboratory testing. Wald’s experience also illustrates that treatment route involves practical tradeoffs: injection anxiety may discourage biologic use, while a once-daily tablet can still be delayed or forgotten. Discussion of how each option would fit the patient’s routine is therefore more informative than assuming a preference for oral or injectable treatment.^38,39

Risk communication is most useful when potential benefits and harms are presented together in clear, clinically meaningful terms. Wald recalled being told that an oral JAK inhibitor carried a boxed warning, which “seemed scary” and initially discouraged her from considering treatment. A subsequent explanation of the warning, the available clinical evidence, and her individual risk factors allowed her to reconsider the option. Discussing absolute risks, expected timing of improvement, monitoring requirements, and uncertainties in higher-risk populations can support informed decisions and uncover concerns that might otherwise lead to treatment refusal or early discontinuation.^37,38

Expectations established at treatment initiation provide a reference point for reassessment. Wald described developing trust when her clinician acknowledged that a partial response remained incomplete and continued to pursue better control. Access, cost, regimen complexity, and adherence also require ongoing review.^16,40 Phone reminders, medication trackers, established routines, and family support may improve consistency, while nonjudgmental questions help distinguish pharmacologic failure from missed doses or access barriers. Revisiting treatment goals, risks, preferences, and feasibility allows the plan to evolve with the patient’s disease and circumstances.

Practical Treatment-Escalation Framework
The 4-step framework shown in Figure 2 begins by confirming inadequate disease control through assessment of lesion extent and severity together with itch, sleep disruption, pain, flare frequency, rescue treatment use, and interference with daily activities. Limited body surface area does not exclude clinically important disease, particularly when sensitive sites are affected.^19,41 Before escalation, clinicians should review adherence, application technique, treatment duration, medication access, and adjunctive skin care and consider infection, allergic contact dermatitis, or an alternative diagnosis. Measurable treatment targets developed with the patient can focus attention on the manifestations causing the greatest burden and provide a basis for evaluating response.⁸

Advanced therapy is warranted when optimized topical treatment remains insufficient or impractical. Selection between a biologic and an oral JAK inhibitor incorporates the desired speed and depth of response, route of administration, monitoring requirements, comorbidities, baseline risks, and patient preferences. Biologics may be favored when long-term safety and limited laboratory monitoring are priorities, whereas an oral JAK inhibitor offers rapid symptom improvement, greater skin clearance, and oral administration for patients with acceptable baseline risks.^21,28,35 Reassessment at approximately 3 months identifies early response, followed by evaluation of the optimal treatment target at 6 months.¹⁴ Achievement of established targets supports continuation; persistent symptoms or functional impairment prompts review of adherence and access, dose optimization, or a change in treatment strategy.

Figure 2. Practical Treatment-Escalation Framework

BSA, body surface area; JAK, Janus kinase.
Developed from references.^{8,14,19, 21,28,35,41}

Conclusion
The expanding range of targeted therapies has made sustained control an achievable goal for many patients with moderate to severe AD. Treatment decisions begin with recognition that visible skin findings provide only 1 measure of disease activity; itch, sleep disruption, psychosocial effects, and interference with daily life remain central to determining whether control is adequate. When optimized topical therapy no longer meets the patient’s needs, escalation can be guided by the desired speed and extent of improvement, long-term safety, comorbidities, route of administration, monitoring requirements, and individual preferences. Biologics and oral JAK inhibitors offer different clinical advantages, making careful risk assessment and shared decision-making integral to selection. Continued reassessment against agreed treatment targets helps identify and address partial responses, adverse effects, access barriers, and adherence difficulties before suboptimal disease control is accepted as the best attainable outcome for the patient.

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