The International Eczema Council has established standardized definitions for low disease activity, very low disease activity, on-drug complete control, and off-drug remission in atopic dermatitis, addressing a longstanding gap in clinical trial benchmarks, according to a consensus statement published in JAMA Dermatology.

The International Eczema Council (IEC) developed the framework through a 3-round modified Delphi process conducted from January to July 2025. The effort was designed for use in clinical trials and translational research, where atopic dermatitis (AD) has lacked harmonized, internationally endorsed thresholds for disease control despite advances in therapies that make sustained control increasingly achievable.

Of 151 experts invited from more than 30 countries, 61 completed round 1, 37 completed round 2, and 103 completed round 3. Respondents included clinician-researchers (66%), clinicians (30%), and researchers (5%), with 8% identifying as patients with lived experience of AD or patient advocacy representatives. Consensus was defined as at least 70% agreement.

Before the Delphi process, an IEC steering committee conducted a targeted literature review of studies published from 2004 through 2024. Six domains were initially considered: clinician-assessed disease activity, patient-reported outcomes, treatment allowance, duration, flare occurrence, and biomarkers. Evidence supported inclusion of the first four domains, while biomarkers and flare occurrence were excluded because no reliable, broadly accessible biomarkers are currently available.

Panelists emphasized that no single measure adequately captures disease burden. In round 1, 89% selected the validated Investigator Global Assessment for Atopic Dermatitis, 71% selected the Eczema Area and Severity Index, and 53% selected body surface area as useful clinician-reported measures. In round 2, most favored combining the validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) and the Eczema Area and Severity Index (EASI) to balance clinical judgment with more detailed disease assessment; the framework recommends capturing both measures when feasible.

The Peak Pruritus Numerical Rating Scale (PP-NRS) was selected as the preferred measure of itch. Investigators noted that a score of 0 was generally considered aspirational rather than consistently achievable, supporting the use of 0/1 thresholds in the final definitions.

The final framework defined four disease states:

• Low disease activity: vIGA-AD of 2, or equivalent Investigator’s Global Assessment score of 2, or EASI of seven or less, plus PP-NRS of four or less at a single time point

• Very low disease activity: vIGA-AD of 0 or 1, or EASI of three or less, plus PP-NRS of 0 or 1 at a single time point

• On-drug complete control: vIGA-AD of 0 or EASI of 0, plus PP-NRS of 0 or 1, maintained for 6 months while receiving AD-related therapy

• Off-drug remission: vIGA-AD of 0 or EASI of 0, plus PP-NRS of 0 or 1, maintained for at least 12 months following discontinuation of medicated AD therapy

In this framework, “drug” excluded only nonmedicated moisturizers and emollients.

Agreement with the final definitions was high, ranging from 95% to 97%. The third Delphi round resolved two key outstanding issues from earlier rounds: the preferred terminology for disease control achieved during treatment and the optimal EASI threshold for low disease activity. Although the threshold approached near-consensus independently, the integrated definition achieved broad agreement.

Panelists favored the term “on-drug complete control” over “on-drug remission,” with 60% preferring the terminology and 95% agreeing with the associated definition. Investigators noted that this distinction may reduce ambiguity around disease control achieved during active treatment.

Qualitative feedback supported the EASI threshold for low disease activity as clinically meaningful and feasible, although some panelists noted that numeric cutoffs may not fully capture disease heterogeneity. Opinions on itch thresholds were more variable, with some favoring stricter cutoffs or alternative scoring approaches. As observed in other immune-mediated diseases, agreement was stronger for clinician-reported measures than for patient-reported outcomes.

The researchers highlighted the need for standardization, noting that inconsistent outcome definitions in other diseases, including psoriasis, have complicated cross-trial comparisons. They positioned the IEC framework as a step toward consistent, comparable outcome measures in AD and a foundation for treat-to-target strategies.

Limitations included uneven geographic representation, variation in participation across Delphi rounds, and limited representation of patients with AD who were not also clinicians or researchers. As a result, the framework may place greater weight on clinician-reported measures. Broader patient-reported outcome tools were reviewed but not incorporated, consistent with the trial-focused scope. The IEC is launching a complementary initiative to better integrate patient-priority outcomes into future frameworks.

“These standardized, clinically meaningful definitions provide a foundation for harmonized trial design, regulatory evaluation, and longitudinal comparative effectiveness research,” the researchers wrote.

Disclosures: The study was sponsored by the International Eczema Council, with partial financial support from a Sanofi grant. Additional methods support was provided by LUCID Group. Authors reported multiple relationships with industry; full disclosures are available in the original article.

Source: JAMA Dermatology