New Treatment Targets for Atopic Dermatitis

Atopic dermatitis of the neck | Image credit: © DermNet

A recent paper published in the Journal of the European Academy of Dermatology and Venereology presents the Aiming High in Eczema/Atopic Dermatitis (AHEAD) recommendations, developed by broad expert consensus to set new treatment targets for atopic dermatitis (AD) across all ages and severities. Informed by a global patient study and insights from 87 leading dermatologists in 44 countries, including the United States, the AHEAD recommendations emphasize a patient-centered approach.^1,2 Patients identify their most burdensome AD symptoms, and clinicians select corresponding patient- and clinician-reported severity and objective measures. Treatment targets are then chosen from a range of "moderate" or "optimal" options, with the ultimate goal of achieving the optimal targets or ‘minimal disease activity’ such as EASI-90 and itch-NRS 0/1. While the focus is on reaching optimal targets, moderate targets represent only partial improvements and are not ideal, but they are considered acceptable when patients have limited access to advanced therapies, serving as a fallback when optimal outcomes are not immediately attainable.¹

A recent real-world study from TARGET-DERM registry³ showed that around one-third of patients treated with advanced systemic therapies (mostly biologics) had inadequate response for skin clearance and two-thirds had inadequate itch relief, after at least 6 months of treatment, highlighting significant therapeutic inertia in moderate-to-severe AD management. 

Background

The chronic physical symptoms of AD such as itchy and painful skin are often associated with affecting patients’ quality of sleep, sexual and social interactions, and work productivity. Due to the mental and physical effects of AD combined with dissatisfaction with current treatment regimens, more effective therapies are needed, according to Silverberg et al. The study authors highlighted previous studies that found that “only 8% of patients with AD and 7% of patients with severe AD are treated with systemic therapies and may therefore not be receiving optimal treatment.”

Silverberg et al addressed that current AD management guidelines may not fully consider the needs of patients. Based on this concept, the study authors reviewed data from a 2022 paper that also recognized that tailored patient treatments are needed for AD. The ethnically diverse and global study by Wollenberg et al included 88 patients from 15 different countries. Wollenberg et al found that itch, skin redness, dry skin, and sleep disturbances were the most frequently reported symptoms of AD; patients felt non-dermatology clinicians underestimated their disease burden; most patients were not familiar with AD severity scoring systems; and patients favored a combination of patient- and clinician-reported outcomes.²

Methods

Seven expert dermatologists met and formed an executive steering committee (ESC) to discuss patient treatment goals in AD and review the 2022 study data. From there, regional dermatology groups consisting of 9 regional sub-committees of approximately 10 dermatologists each were created, representing 87 dermatologists across 44 countries. The ESC used Wollenberg et al’s qualitative data to draft clinical recommendations. Out of the 87 dermatology experts, 77 (89%) participated in an eDelphi voting process to rate the recommendations from 1 (strongly disagree) to 10 (strongly agree). Consensus agreement for a recommendation was pre-defined as ≥70% of all experts rating agreement as 7 (mildly agree), 8 (moderately agree), 9 (agree), or 10 (strongly agree); strong consensus was defined as ≥90% agreement.

Results

During the eDelphi voting process, consensus was reached for all recommendations in the first round of voting, with 88% of the recommendations (30/34) reaching a ‘strong’ consensus. The mean score for all recommendations ranged from 7.89 to 9.76.

In total, 34 AHEAD recommendations were developed that focused on disease severity assessments, treatment goals and targets, clinician- and patient-reported outcome targets, long-term disease control, and a “novel AHEAD approach.”

Key recommendations from each category include:

1. The optimal target for skin clearance should be EASI-90 or EASI ≤3 (clear or almost-clear skin)
2. The optimal target for itch relief should be itch NRS 0/1 (minimal or no itch)
3. Treatment response can be considered inadequate if the agreed targets are not met within 3–6 months; treatment modification or escalation should then be considered
4. The ultimate treatment goal in AD should be a satisfied patient with minimal impact on quality of life, clear/almost-clear skin with no/minimal itch
5. Physicians should consider assessment of long-term disease control because disease activity on the day of the appointment may not reflect the patient's overall condition over the previous weeks or months

Recommendations for disease severity assessment and treatment targets reached a strong consensus with a mean agreement of 98.1%. Overall, the disease severity and treatment target recommendations state that clinician- and patient-reported outcomes should be used for shared-decision making. The group of experts also agreed that it is feasible to aim for higher treatment targets to improve patient outcomes due to more effective therapies and that the main goal while treating patients should be a “satisfied” patient.

Additional results include 76 out of 77 experts agreed that clinicians should consider assessment of long-term disease control and most of the group (93.3% mean agreement) agreed that clinicians and patients should aim for long-term disease control, minimal flares, and achievement of MDA. The group of experts also agreed that clinicians should consider using the Atopic Dermatitis Control Tool (ADCT) or Recap of Atopic Eczema (RECAP) to assess disease control.

Based on their results, the group of experts developed the AHEAD approach. With this new model, patients are asked to select 1 to 3 disease symptoms or features of AD that they want to resolve the most. The clinician then chooses patient-reported outcome measures corresponding to the patient's selected AD symptoms. The clinician should also choose at least one clinician-reported outcome measure to have an objective measure of the patient’s overall AD. The final step instructs the clinician and patient to discuss the selected clinician- and patient-reported outcomes and select either ‘moderate’ or ‘optimal’ treatment targets. The achievement of optimal treatment targets is defined as MDA.

“Although experts agreed that clinicians and patients/caregivers should aim for higher (optimal) targets wherever possible, they also agreed that these targets may be difficult to achieve in some patients, so lower, ‘moderate’ targets were included as alternatives. Recommendations also provide guidance on treatment escalation or modification as well as eligibility for systemic therapy,” wrote Silverberg et al.

Regarding treatment targets, all recommendations reached consensus, with 15 of 18 reaching a strong consensus or 92.9% mean agreement. Two recommendations that did not achieve a strong consensus were related to recognizing mental health conditions as features of AD. Another recommendation that did not achieve a strong consensus was the optimal target for skin pain. Some experts believe that skin pain is a “non-specific phenomenon” for AD and needs further clarification.

All recommendations for the AHEAD approach achieved consensus. One recommendation did not achieve a strong consensus, which related to patients choosing the AD features most important to them. Most experts agreed that patients should choose up to 3 AD features, however, some experts expressed that the number of selected features should not be limited.

Practical Considerations and Conclusion

In their review, Silverberg et al addressed that previous consensus recommendations were limited in their inclusion of global insights and evidence-based patient perspectives. In 2021, a treat-to-target initiative enrolled 10 patient representatives to participate in eDelphi voting, however, they were only from European countries and Australia. Additionally, the 2021 initiative included 77 clinicians from 28 predominantly European countries and, “clinician participation in eDelphi voting was low, with 61.0% (n = 47) and 58.4% (n = 45) of clinicians voting in rounds 1 and 2, respectively.”⁴

According to Silverberg et al, their AHEAD recommendations are based on ethnically diverse, global, qualitative patient research.2 Their initiative also included 87 dermatologists from 44 countries and high eDelphi voting (n=77).

“Contrary to the more rigid and physician-centric approaches used in prior recommendations and initiatives, the AHEAD recommendations recognize a patient's unique reasons for making treatment decisions and therefore expand on the individualized approach as per that suggested in the ‘treatable traits’ concept,” wrote Silverberg et al.

For clinicians, the targets in AHEAD may be ambitious due to the period of 3 to 6 months, however, providing moderate and optimal targets allows for a more patient-focused and flexible approach.

“The consensus-based AHEAD recommendations establish a novel approach to AD clinical practice that combines treat-to-target principles with shared decision-making. They will optimize AD management with higher treatment targets and increased patient involvement compared with the current standard of care, for patients at all ages and severities. Future endeavors will involve the development of a tool to help implement the AHEAD recommendations in real-world clinical practice and studies to assess their feasibility and clinical value,” concluded Silverberg et al.

References

1. Silverberg JI, Gooderham M, Katoh N, et al. Combining treat-to-target principles and shared decision-making: International expert consensus-based recommendations with a novel concept for minimal disease activity criteria in atopic dermatitis. J Eur Acad Dermatol Venereol. Published online July 11, 2024. doi:10.1111/jdv.20229

2. Wollenberg A, Gooderham M, Katoh N, Aoki V, Pink AE, Binamer Y, et al. Understanding the impact of atopic dermatitis on patients: a large international, ethnically diverse survey-based qualitative study. Poster presented at 2022 Revolutionizing Atopic Dermatitis Virtual Conference; December 11, 2022.

3. Eichenfield LF, Grada A, Knapp KD, Munoz B, Crawford JM, Silverberg JI. 568-Persistent inadequate disease control and therapeutic inertia in moderate-to-severe atopic dermatitis: a 12-month longitudinal analysis of real-world outcomes from TARGET-DERM registry. Br J Dermatol. 2024 Feb;190 (Supplement_2):ii60-1.

4. De Bruin-Weller M, Biedermann T, Bissonnette R, Deleuran M, Foley P, Girolomoni G, et al. Treat-to-target in atopic dermatitis: an international consensus on a set of core decision points for systemic therapies. Acta Derm Venereol. 2021;101(2):adv00402. Published 2021 Feb 17. doi:10.2340/00015555-3751