New Biologics for the Treatment of Atopic Dermatitis: Analysis of Efficacy, Safety, and Paradoxical Atopic Dermatitis Acceleration

Abstract

Atopic dermatitis (AD) is a chronic, inflammatory skin disease with an eczematous rash and itching. Due to undesired adverse effects of traditional systemic treatment, there is still an unmet need for safe and effective long-term therapy for refractory AD. As our understanding of the pathogenesis underlying AD grows, novel treatments targeting specific molecules have been developed. Here, we discuss the efficacy and safety profiles of these drugs in recent clinical trials. Among their adverse effects, of particular note is AD acceleration. Although there is still debate about whether certain adverse reactions can be said to be paradoxical adverse events (PAEs), a wide range of PAEs have been reported during biological treatment for chronic immune-mediated diseases. Close surveillance of novel biologics is crucial to detect new undescribed paradoxical reactions and to shed light on the convoluted pathogenesis of AD.

Overlapping Features of Psoriasis and Atopic Dermatitis: From Genetics to Immunopathogenesis to Phenotypes

“…TNF-ai accounted for the most cases of eczematous reaction, and these cases have been discussed as tumor necrosis factor-alpha inhibitor-associated dermatitis [ 81 , 84 ]. Strong expression of IL-36, beta-defensin 2, Th2 cells, and Th17 cells were observed in the biopsy specimen from the PSO lesions of these cases [ 85 ].…”

“…In contrast, IL-23i was rarely implicated in paradoxical eczematous reactions. Although this could be partially explained by the latest launch of IL-23i, data implied that IL-23i might have a lesser probability of inducing paradoxical eczema than IL-17i [ 81 , 84 ]. The onset time of eczema after starting biologics ranged widely, but mostly within 6 months [ 81 ].…”

“…Third, genetic susceptibility might play a part. The polymorphism of AD genes might explain why the same biologic agent results in resolution in one person but triggers paradoxical AD in another [ 81 , 84 , 87 ].…”

OX40-OX40L Inhibition for the Treatment of Atopic Dermatitis—Focus on Rocatinlimab and Amlitelimab

“…The currently available treatment armamentarium includes topical therapy (topical corticosteroids, calcineurin inhibitors crisaborole and ruxolitinib), phototherapy, and systemic therapy (conventional immunosuppressants and advanced target therapies). Conventional systemic immunosuppressive therapies may have limited efficacy and harbor long-term toxicity, which makes them not appropriate for continuous use [3,4]. Fortunately, in recent years, several new therapeutic options targeting specific cytokines, cytokine receptors, or intracellular signaling pathways have been developed, showing significant clinical benefits in patients with AD and paving the way for more effective and safer therapies [3][4][5][6].…”

“…Conventional systemic immunosuppressive therapies may have limited efficacy and harbor long-term toxicity, which makes them not appropriate for continuous use [3,4]. Fortunately, in recent years, several new therapeutic options targeting specific cytokines, cytokine receptors, or intracellular signaling pathways have been developed, showing significant clinical benefits in patients with AD and paving the way for more effective and safer therapies [3][4][5][6]. Dupilumab, a fully human IgG4 monoclonal antibody directed against the IL-4Rα subunit of IL-4 and IL-13 receptors, changed the AD treatment paradigm as it was in 2017 as the first biological drug approved for the treatment of AD [5,6].…”