Early Intervention: Shutting Down AD’s Atopic March

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Timely systemic treatment targeting the immune dysregulation behind atopic dermatitis (AD) could modify the progression of the disease and improve overall patient outcomes, according to a new commentary.

The commentary, “Insights into Early Systemic Treatment in Atopic Dermatitis: Scientific Facts and Practical Considerations,” appeared in the journal Dermatology and Therapy on February 28.¹

Proactive systemic treatment of AD can “modify disease progression, leading to pruritus alleviation, enhanced quality of life, less reliance on intensive topical treatments, improved psychological well-being, and secondary complications prevention,” the authors wrote.

Efstratios Vakirlis and Stamatios Gregoriou, et al, of the department of dermatology and venereology at Aristotle University in Thessaloniki, Greece, noted that “recent advancements in systemic treatments and a deeper understanding of similar skin diseases, such as psoriasis, have highlighted the importance of early intervention” in AD. They examined the potential benefits of early systemic intervention of AD, using pruritis as a measure in treatment decision-making.

“Early systemic intervention may minimize systemic inflammation, halting the ‘atopic march’ and disrupting the ‘itch–scratch’ cycle,” Vakirlis, Gregoriou et al wrote. AD is strongly associated with the development of food allergies, asthma, and allergic rhinitis, known as the “atopic march.”

“The key point in early systemic treatment could be most likely pruritus, a hallmark symptom, and a central driver of the self-perpetuating “itch–scratch” cycle that characterizes AD,” the authors wrote.

Investigators cited previous research suggesting possibly advantageous times for early intervention:²

• The presymptomatic stage, when the use of emollients could remedy microbioma dysfunction
• The stage of initial activation of innate immunity
• The stage of activation of the adaptive immune response

Approaches that inhibit the escalation of inflammatory response before visible skin lesions develop will be most likely to disrupt the atopic march driven by type 2 inflammation, they wrote.

Although AD severity is typically measured using the Eczema Area Severity Index (EASI) or Scoring of Atopic Dermatitis (SCORAD) measurement, the authors noted, these tools do not capture “clinically invisible” inflammation and may underestimate disease activity.

Biologics have an effect in attenuating the atopic march, they wrote, but “nonetheless, more extensive and long-term trials spanning diverse age cohorts and disease severity are needed to validate this effect and substantiate whether biologics can consistently and durably rectify the inherent immune skew toward type 2 inflammation, the fundamental basis of the atopic march.”

Dermatology Times previously reported on a study that showed that patients with AD treated with the biologic dupilumab had a 34% reduction in new or worsened allergies (Incidence rate ratio [IRR] 0.66; 95% CI, 0.52-0.84) and a 37% reduction in new allergies (IRR 0.63; 95% CI, 0.48-0.83), a positive step in slowing the atopic march.³

“Controlling the signaling of the cytokine IL-4 may be an important treatment option for halting the atopic march,” according to the Dermatology Times article. “Dupilumab is a monoclonal antibody that blocks IL-4R and has been effective in treating moderate to severe AD and asthma, as well as other diseases caused by type 2 inflammation.”

References 

1. VakirlisE, Gregoriou S, BakirtziK,et al. Insights into early systemic treatment in atopic dermatitis: scientific facts and practical considerations. Dermatol Ther (Heidelb) (2024). https://doi.org/10.1007/s13555-024-01110-6
2. Bieber T. Atopic dermatitis: an expanding therapeutic pipeline for a complex disease. Nat Rev Drug Discov. 2022;21(1):21–40.
3. Raglin H. Dupilumab effective in reducing new allergies and slowing atopic march. Dermatology Times. July 8, 2023. Accessed February 28, 2024. https://www.dermatologytimes.com/view/dupilumab-effective-in-reducing-new-allergies-and-slowing-atopic-march