An expert panel convened by the International Eczema Council (IEC) has issued a consensus statement to create standardized definitions of low disease activity (LDA) and remission in atopic dermatitis (AD).

“The major clinical value is that this gives the field a common language for what meaningful disease control actually looks like,” lead statement author Joseph Merola, MD, MMSc, professor of dermatology and rheumatology at the University of Texas Southwestern Medical Center in Dallas, told Medscape Medical News.

The statement, published in JAMA Dermatology, provides standardized definitions for different stages of disease activity, Merola noted, namely LDA very LDA (vLDA), and remission. “As therapies have improved, these states are increasingly achievable, but without shared definitions it has been difficult to compare trial results, interpret outcomes consistently, guide regulatory discussions or bring a true treat-to-target framework into practice,” he said. “This consensus statement helps address that gap.”

In an accompanying editorial, authored by Hywel Williams, DSc, professor of dermato-epidemiology and codirector of the Center of Evidence-Based Dermatology, Lifespan and Population Health at the University of Nottingham School of Medicine, Nottingham, England, wrote the panel’s effort to standardize definitions “is to be commended.”

However, he took issue with the “lack of meaningful patient/carer/public engagement” in the process, which he called “a substantial weakness.” He also called the “lack of alignment” of the IEC initiative with the definitions of treat-to-target goals of the Aiming High in Eczema/Atopic Dermatitis effort to determine best response for domains such as Eczema Area and Severity Index (EASI) and itch “a missed opportunity.”

Defining Disease States

The IEC consensus statement includes four definitions intended for use in clinical trials and translational research:

• LDA: validated Investigative Global Assessment for AD (vIGA-AD) (or equivalent IGA) ≤ 2 or EASI ≤ 7, plus patient-reported Peak Pruritus Numerical Rating Scale (PP-NRS) ≤ 4.
• vLDA: vIGA-AD (or equivalent IGA) of 0/1 or EASI ≤ 3, plus patient reported PP-NRS of 0/1.
• On-drug complete control: vIGA-AD (or equivalent IGA) of 0 or EASI of 0, plus patient reported PP-NRS of 0/1, maintained for 6 months or more concurrently while on therapy.
• Off-drug remission: vIGA-AD (or equivalent IGA) of 0 or EASI of 0, plus patient-reported PP-NRS of 0/1 maintained concurrently for at least 12 months after discontinuation of medicated AD therapy.

The process the panel used, described as a modified Delta initiative, involved 151 subject matter experts, including 17 (8%), who self-identified as either patients, caregivers, or patient advocates.

Merola said the process was “a major strength of the work” that enabled a “global, structured consensus.” The initiative used predefined agreement thresholds, multiple rounds of review, and feedback from experts with “deep experience” in AD, outcomes research, instrument validation, trial design, and regulatory considerations, he noted. “That matters because any framework intended for broad uptake in trials has to be credible internationally and acceptable across regulatory environments.”

The modified Delphi process allowed the participants to work through matters on which they may not have agreed, Merola added. “For example, there was careful discussion around terminology, time requirements, and symptom thresholds,” he explained. “In the end, the framework reflects a pragmatic balance between clinical meaning, feasibility and patient relevance.”

He added that patient involvement was “an important part” of the process, “even though the initiative was intentionally structured as a trial-facing expert consensus process.” Patient input is a key reason itch is a central component of the standards and also a reason the PP-NRS was used to anchor all the four definitions, Merola said.

“At the same time, we are very open that this is not the end of the patient-voice conversation,” Merola said. Hence, he noted, the IEC is launching a separate patient-focused initiative to further develop and validate measures where needed.

By providing consensus-derived definitions, the statement addresses inconsistencies surrounding descriptions of AD remission, Merola said. “Different trials and different groups have used different benchmarks, which makes it much harder to compare therapies across studies or understand how close we are to achieving outcomes that really matter to patients,” he said. That inconsistency also complicates regulatory issues and comparisons between trials, Merola said.

“Clinically, the absence of standard targets has also made it harder to define success in a consistent way with patients,” he added. “One clinician may think a patient is doing very well based on skin signs, while the patient may still be burdened by itch or other symptoms.”

“One of the important conceptual advances in this work is the modular framework that recognizes clinician-reported signs and patient-reported symptoms as complementary but distinct components of disease control.”

Clinician, Patient Expectations Diverge

In comments to Medscape Medical News, Williams explained patient involvement in the process of defining disease states is important to how clinicians use the standards b ecause of the increasing role of shared-decision making in disease management. “In other words,” he said, “what makes a clinician happy, like an area of skin that appears to look clear at that point in time, may not be what makes the patient happy in terms of symptoms or quality of life or treatment burden.”

He noted his commentary used the phrase “looking better but feeling worse.” He added, “so when it comes to something like defining remission, a patient view of what remission feels like is as important as what it looks like to a clinician.”

Williams credited the IEC panel for incorporating patient perspectives in developing proposed definitions that included “something that clinicians see,” including EASI or vIGA standards, and “something that patients experience,” such as itch.

But, he said, “given the nature of modern shared decision-making in determining treatment goals, the proportion should have been more like 50%,” rather than 18%.

Williams also said the statement lacked clarity of how to use EASI or vIGA to evaluate disease activity. “For example, should they be measured daily? Just impossible as EASI or vIGA require a clinic visit with all the expense and inconvenience associated with such visits. Or monthly? Still a hassle for routine clinical practice. Or every 3 months? Serious risk now of missing intervening flares.”

‘An Important Step’ Forward

Asked to comment, Peter Lio, MD, professor of dermatology and pediatrics at Feinberg School of Medicine at Northwestern Medicine in Chicago, who was not an author, said the modified Delphi approach was a “major strength” of the statement.

Future efforts would benefit from greater patient involvement, he added. “Patient perspectives are essential when defining concepts like disease control or remission because those states are not purely clinical,” he noted. “At the same time, this initiative represents an important first step,” and “opens the door to more patient-centered refinements as the definitions are tested and applied,” he said.

This work was sponsored by the IEC, with financial support provided in part by a grant from Sanofi for methods development and additional methods support from LUCID Group. Merola reported having financial relationships with Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, AbbVie, Eli Lilly, Moonlake, Novartis, Janssen, Oruka, UCB, Sanofi and Regeneron Pharmaceuticals. Other author disclosures are available in the study. Williams reported being an adviser to Harmonising Outcome Measures for Eczema.

Lio reported having financial relationships with Akeyna, Alphyn Biologics, AbbVie, Almirall, Amyris, Apogee, Arcutis, Astria Therapeutics, Castle Biosciences, Codex Labs, Concerto Biosci, Dermavant, Eli Lilly, Galderma, Incyte, Kenvue, La Roche-Posay/L’Oreal, LEO Pharma, Lipidor, L’Oreal, Merck, Micreos, MyOR Diagnostics, Nektar Therapeutics, Nia Health, Pelthos Therapeutics, Novartis, Pfizer, Pierre-Fabre Dermatologie Phyla, Regeneron/Sanofi Genzyme, Sibel Health, Skinfix, Song Lab Skincare, Soteri Skin, Stratum Biosciences, Sun Pharma, Theraplex, Thimble Health, Topaz Biosciences, Unilever, Verdant Scientific, Verrica and Yobee Care.

Richard Mark Kirkner is a medical journalist based in Philadelphia.