Overcoming Therapeutic Inertia in Atopic Dermatitis—The AHEAD Recommendations as a Path Forward

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Atopic dermatitis (AD) remains a challenging condition to manage effectively, and despite advances in treatment, there is a persistent issue of therapeutic inertia in the field. This inertia, characterized by the failure to escalate treatment when patients do not meet their therapeutic targets, continues to undermine patient outcomes. The TARGET-DERM registry longitudinal study has highlighted this issue in the real-world, showing that many patients with moderate-to-severe AD remain undertreated, leading to inadequate disease control and reduced quality of life.^1,2

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

To overcome therapeutic inertia, we must adopt these AHEAD recommendations, which encourage clinicians to aim for Minimal Disease Activity (MDA) by reaching optimal treatment targets. MDA means achieving optimal targets for one patient-reported outcomes (such as itch), and one clinician-reported outcomes (such as skin clearance).  

AHEAD consensus provided optimal targets for many outcomes. However, since itch is the most burdensome symptom reported by AD patients, and skin rash is the most important sign for AD. I think those two outcomes are the most important and feasible to assess in a busy daily practice. Achieving optimal targets for both itch and skin lesions would be MDA and aligns with AHEAD recommendation.

For clinicians who don’t use EASI measures for skin clearance, IGA x BSA would be an alternative option. 

Below is a summary of the optimal targets for itch and skin clearance:

What Constitutes an Inadequate Response, and When Should Therapy Be Switched?

The AHEAD recommendations provide clear guidance on defining an inadequate treatment response and determining when to consider switching therapies. According to these guidelines, a treatment response is deemed inadequate if the agreed-upon targets are not achieved within 3–6 months, at which point treatment modification or escalation should be considered. This is particularly important given the availability of advanced therapies that can enable patients to achieve both EASI-90 (90% improvement in skin clearance) and an itch NRS of 0/1. The LEVEL UP study, a head-to-head comparison of Upadacitinib versus Dupilumab in patients with moderate-to-severe AD, has demonstrated the potential of such therapies to deliver these outcomes. Additionally, ongoing SWITCH studies are expected to provide valuable, practice-informing evidence, offering insights not only into efficacy but also into patient-reported outcomes, which are integral to the AHEAD recommendations.

Christopher Bunick, MD, PhD, is an associate professor of dermatology at Yale University in New Haven, Connecticut, Dermatology Times’ 2024 Winter Editor in Chief, and an expert in immune-mediated and inflammatory skin disorders. His insights into therapeutic strategies emphasize the importance of setting higher standards in dermatologic 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 TARGET-DERM registry. Br J Dermatol. 2024 Feb;190(Supplement_2):ii60-1.
2. Simpson B, Grada A, Knapp KD, Munoz B, Crawford JM, Silverberg JI. 569-Impact 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 of Dermatol. 2024 Feb;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: International expert consensus‐based recommendations with a novel concept for 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 levels of itch relief and skin clearance 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.