Efforts to define disease control highlight scientific ambition and practical gaps for clinicians navigating a relapsing condition.
Clear or near-clear skin is no longer an aspirational endpoint but an increasingly achievable reality for patients with atopic dermatitis.
However, the dermatology field is now confronting a more complex challenge – what, exactly, constitutes remission in a disease defined by unpredictability and relapse.
This question is explored in a new editorial by Professor Hywel Charles Williams, writing in an editorial published earlier this month in JAMA Dermatology.
Professor Williams is professor of Dermato-Epidemiology and co-director of the Centre of Evidence Based Dermatology, Faculty of Medicine and Health Sciences at the University of Nottingham.
“The previous concept of disease control involving a stepwise approach using sequential treatments until treatment failure occurs now requires a more ambitious approach of disease modification that involves induction and maintenance of remission,” he wrote.
“Exciting though this may be, it is not useful to talk about concepts such as disease remission unless they are defined so that meaningful comparisons between studies can be made, especially for systematic reviews that underpin evidence-based decision-making.”
Examining recent consensus work led by the International Eczema Council, he said that while the shift from stepwise disease control to a remission-focused, disease-modifying paradigm reflected therapeutic progress, the lack of a robust, universally accepted definition risked undermining both clinical practice and research comparability.
“It is a challenging area, as the concept of remission in atopic dermatitis (AD) is especially difficult because the disease is typically chronic and relapsing. Inflammatory flares can occur rapidly within one to two days and spontaneous remissions can occur, making it difficult to define a universal standard for all patients,” he wrote.
The issue was not merely semantic, Professor Willams said. Without standardised criteria, clinicians and trialists faced difficulty interpreting outcomes, synthesising evidence and setting meaningful treatment targets.
Atopic dermatitis posed particular challenges because of its inherently chronic, relapsing nature. Flares could develop within days, while spontaneous improvements may occur unpredictably, complicating any attempt to define sustained remission across diverse patient populations.
The IEC’s proposed framework, developed through a Delphi consensus process, sought to bring structure by combining clinician-reported signs, such as Eczema Area and Severity Index scores, with patient-reported symptoms like itch severity. It distinguished between low disease activity, very low disease activity and remission both on and off treatment.
However, Professor Williams said there were several limitations that may temper its immediate applicability.
Despite existing recommendations from the Harmonising Outcome Measures for Eczema initiative to include symptoms, signs, quality of life and long-term control, the IEC definitions rely primarily on visible disease and itch intensity. This exclusion of validated long-term control measures may weaken the framework’s ability to capture the full patient experience, particularly over extended periods, Professor Williams said.
Practicality was another sticking point. The proposed definition of off-treatment remission – requiring sustained minimal disease activity over at least 12 months – depended on repeated assessments that may be burdensome for patients and costly for health systems.
“Anything less than daily recording for PP NRS risks running into recall problems. Itch is the dominant symptom of AD, but a daily itch of 0 to 1 (on a scale of 10) over 12 months, although ambitious, sounds very low, especially when one considers contamination by non-AD itch,” Professor Williams wrote.
“Determining feasibility and defining the frequency of measurement of the chosen domains is almost as important as the choice of the domains if harmonisation of a workable definition of low disease activity/remission over time is to be achieved.”
The composition and conduct of the consensus process also draw scrutiny from Professor Williams.
“The expert steering committee was composed of mainly US AD dermatologists and trialists who were experienced in measuring treatment outcomes, and most declared long lists of conflicts of interest within the pharmaceutical industry,” he wrote.
“The study was made possible through a grant from Sanofi, who manufactures dupilumab, a targeted therapy for AD.
“Given that one of the project aims was to accommodate regional regulatory frameworks, it was surprising not to have formal inclusion of regulators such as the US Food and Drug Administration, Pharmaceuticals and Medical Devices Agency or European Medicines Agency in this exercise.”
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For clinicians, he noted the implications were mixed. The push towards standardising remission was widely welcomed, particularly as newer targeted therapies made sustained disease control more attainable.
The emphasis on integrating both signs and symptoms also aligned with efforts to avoid discordance between clinical improvement and patient wellbeing.
Yet the current definitions may be difficult to operationalise without further refinement, especially in routine practice settings, Professor Williams wrote.
Ultimately, his editorial framed the IEC initiative as an important first step rather than a definitive solution, underscoring the need for broader stakeholder engagement, alignment with existing frameworks, and real-world testing to determine whether proposed definitions are both meaningful and workable.
“Conducting international consensus work for concepts such as disease control and remission in rapidly fluctuating inflammatory diseases such as AD is not easy,” Professor Williams concluded.
“The IEC are to be congratulated for their pioneering attempts to start the process and for exposing some of the key conceptual and practical issues that now need to be addressed.”
