Current Directions in Targeted Therapy of the Atopic Dermatitis

Advances in researches on the pathogenesis of atopic dermatitis and potential therapeutic targets have resulted in the emergence of many new therapeutic agents targeting specific cytokines, their receptors, or intracellular signaling pathways – biological agents and systemic synthetic inhibitors for targeted therapy. Purpose – to analyze the published data and compare the efficacy and safety of new and registered pharmpreparations for targeted therapy of adult patients with moderate and severe atopic dermatitis. The authors have analyzed randomized controlled trials on current targeted drugs used in atopic dermatitis; they also have analyzed large medical databases. The obtained data were assessed in terms of achieved response of the analyzed preparations by EASI-75 scale and by their safety profile. The authors have also studied the information on registered biological preparations (Dupilumab) and Janus kinase (JAK) inhibitors such as abrocitinib, upadacitinib, baricitinib, as well as on those preparations which are undergoing clinical trials: JAK1/3 inhibitor gusacitinib; interleukin (IL) 4Ra inhibitors – rademikibart, stapokibart and manfidocimab; IL-13Ra inhibitors – eblaxakimab and OX40 and OX40L inhibitors – rocatinlimab and amlitelimab, respectively. Significant differences in their efficacy and their safety profile were noted. For example, biological drugs demonstrated lower risk of serious side effects compared to JAK inhibitors. Besides, the period of effect onset and the need for laboratory monitoring of these drugs had also important clinical difference. Despite the moderately increasing clinical effect, biological preparations have such a safety profile that allows not to conduct strict regular monitoring of laboratory parameters, which makes this group of drugs more preferable in case of concomitant pathology in patients and impossibility or complexity of dynamic control. However, some preparations have quite common specific adverse effects. JAK inhibitors are the preparations of choice for the rapid relief of symptoms of atopic dermatitis, especially in patients resistant to biological drugs. Adverse events have a wide spectrum of manifestations, but their incidence is low. Further studies are needed on the efficacy and safety of monoclonal antibodies for long-term use, on synthetic targeted drugs, on combined therapeutic regimens, as well as on the effect of episodic intake of these drugs by the patients with atopic dermatitis.