Overcoming therapeutic inertia in atopic dermatitis – the AHEAD recommendations as a way forward

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Atopic dermatitis (AD) remains a challenging disease that is difficult to treat effectively, and despite advances in treatment, there is a persistent problem of therapeutic inertia in the field. This inertia, characterized by the failure to intensify treatment when patients do not achieve their therapeutic goals, continues to compromise treatment outcomes. The longitudinal study of the TARGET-DERM registry has highlighted this problem in practice, showing that many patients with moderate to severe AD remain undertreated, resulting in inadequate disease control and reduced quality of life.^1.2

The recently published recommendations of the Aiming High in Eczema/Atopic Dermatitis (AHEAD) initiative provide a much-needed framework to combat this inertia.³ By setting higher treatment goals, the AHEAD recommendations emphasize the importance of achieving optimal goals for both skin clearance and itch relief. These goals are not only desirable; they are essential to improving patient outcomes. Another TARGET-DERM registry study further supports this, showing that patients who achieve higher levels of skin clearance and itch relief have significantly better sleep and quality of life outcomes than those who experience only partial improvement.⁴

To overcome therapeutic inertia, we must adopt these AHEAD recommendations that encourage clinicians to strive for minimal disease activity (MDA) by achieving optimal treatment goals. MDA means achieving optimal goals for a patient-reported outcome (such as pruritus) and a clinician-reported outcome (such as skin clearing).

The AHEAD consensus provided optimal targets for many outcomes. However, since itch is the most distressing symptom reported by AD patients and rash is the most important sign of AD, I think these two outcomes are the most important and easiest to assess when one has a busy day. Achieving optimal targets for both itch and skin lesions would be MDA and consistent with the AHEAD recommendation.

For clinicians who do not use EASI measurements for skin cleansing, IGA x BSA would be an alternative option.

Below is a summary of the optimal targets for relieving itching and skin irritation:

What constitutes an inadequate response and when should therapy be changed?

The AHEAD recommendations provide clear guidelines to define inadequate treatment response and determine when a change in therapy should be considered. According to these guidelines, treatment response is considered inadequate if agreed goals are not achieved within 3–6 months, at which point treatment adjustment or escalation should be considered. This is particularly important given the availability of advanced therapies that can help patients achieve both EASI-90 (90% improvement in skin clearing) and an itch NRS of 0/1. The LEVEL UP trial, a head-to-head comparison of upadacitinib and dupilumab in patients with moderate to severe Alzheimer’s disease, has demonstrated the potential of such therapies to achieve these outcomes. In addition, ongoing SWITCH trials are expected to provide valuable, real-world evidence and provide insights not only into efficacy but also into patient-reported outcomes, which are an integral part of the AHEAD recommendations.

Christopher Bunick, MD, PhDis Associate Professor of Dermatology at Yale University in New Haven, Connecticut, Dermatology Times‘ Editor-in-Chief of the Winter 2024 issue and an expert in immune-mediated and inflammatory skin diseases. His insights into therapeutic strategies underscore the importance of higher standards in dermatological care.

References

1. 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 the TARGET-DERM registry. Br J Dermatol. February 2024;190(Supplement_2):ii60-1.
2. Simpson B, Grada A, Knapp KD, Munoz B, Crawford JM, Silverberg JI. 569 – Effects of therapeutic inertia on patient-reported outcomes in moderate to severe atopic dermatitis: a 12-month longitudinal study from the TARGET-DERM AD registry. Br J by Dermatol. February 2024;190(Supplement_2):ii61-2.
3. Silverberg JI, Gooderham M, Katoh N, Aoki V, Pink AE, Binamer Y, Rademaker M, Fomina D, Gutermuth J, Ahn J, Valenzuela F. Combining treat-to-target principles and shared decision-making: recommendations based on international expert consensus with a new concept of minimal disease activity criteria in atopic dermatitis. J Eur Acad Dermatol Venere. 2024.
4. Silverberg JI, Knapp KD, Munoz B, Crawford JM, Calimlim B, Obi C, Grada A, Paller AS. 709 – Greater itch relief and skin clearing correlate with improved patient outcomes in atopic dermatitis – real-world insights from TARGET-DERM AD. Br J Dermatol. 2024 Aug;191(Supplement_2):ljae266-083.