February 2025 digest

Towards a Better Definition of Therapeutic Concepts in Atopic Dermatitis: Learning from Rheumatoid Arthritis

Dear Colleagues, Dear Friends,

Since the 1980s, rheumatoid arthritis (RA) has served as a model for therapeutic strategies in chronic inflammatory diseases. RA activity is assessed using multiple measures, including swollen joint counts, inflammatory markers, and radiographic signs of joint damage. In the 1990s, a core set of disease activity measures was established, leading to widely used RA composite scoring systems. The concept of “tight control” emerged, emphasizing frequent disease activity assessments to guide treatment adjustments.

The introduction of disease-modifying anti-rheumatic drugs (DMARDs) in the 1980s marked a turning point, distinguishing agents that slow joint damage from nonsteroidal anti-inflammatory drugs (NSAIDs), which provide only symptomatic relief. Over time, the treatment goal shifted toward remission, initially defined as the absence of arthritis symptoms and a normal erythrocyte sedimentation rate (ESR) for two months. Composite scores were later adopted to quantify remission and disease activity levels. The treat-to-target (T2T) approach was developed to achieve remission through aggressive inflammation control using DMARDs, biologics (bDMARDs), and targeted synthetic DMARDs (tsDMARDs). However, given that remission is not always attainable, low disease activity (LDA) emerged as an alternative therapeutic goal. In patients maintaining remission, DMARD dose reduction strategies have been explored. While no biomarkers reliably predict DMARD response, early clinical improvement within three months is crucial for guiding treatment under the T2T strategy.

In contrast, therapeutic concepts in atopic dermatitis (AD) remain underdeveloped. AD severity is assessed using numerous scoring systems, with the Investigator Global Assessment (IGA) preferred by the FDA for regulatory purposes rather than practical clinical guidance. Treatment goals primarily focus on symptom control, lesion improvement, and enhanced quality of life. Until 2017, severe AD was managed with anti-inflammatory agents such as methotrexate, azathioprine, and cyclosporine, often in combination with topical steroids and immunomodulators. The advent of dupilumab, the first biologic targeting IL-4 and IL-13, represented a paradigm shift. Dupilumab is considered the first disease-modifying therapy for AD, as it restores the skin barrier, normalizes the microbiome, and reduces allergen sensitization. Whether early intervention with dupilumab can modify the disease course and prevent progression to other allergic conditions remains in 2025 a key research question.

The concept of remission in AD is further complicated by the fact that spontaneous remission is common—over 40% of early-onset cases resolve by age three. A set of definitions was proposed in 2015 by the European task force on AD (DOI: 10.1111/jdv.13599). However, there is no international consensus on a standardized definition of remission or remission on treatment. A recent multidisciplinary review (DOI: 10.1016/j.eclinm.2024.103050) proposes a remission definition based on four criteria: absence of skin signs, no itching, normal sleep, and no need for systemic steroids for at least one year. These criteria would be easily assessed in clinical practice using a single composite score such as the SCORAD index.

The authors aptly underline that future research should focus on defining remission and LDA in AD to establish a treat-to-target framework, mirroring RA management strategies. Additionally, dose reduction strategies for long-term treatment optimization remain a priority. Further studies are also needed to determine whether early biologic intervention can prevent non-allergic comorbidities.

Map by Chris55 – Data from World Health Organization Estimated Deaths 2012 Vector map from BlankMap-World6 by Canuckguy et al., CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=50321308

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Best wishes,

Alain TAÏEB
President ISAD

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