How to Understand Personalized Medicine in Atopic Dermatitis Nowadays?

Abstract

Atopic dermatitis (AD) is a heterogeneous disease in terms of its phenotypical, barrier, and immunological presentation. Emerging therapies are undoubtedly contributing to a new chapter in the treatment of AD, bringing an excellent possibility of individualization, and thereby creating a tailored approach. The two most promising substance groups are biological drugs (dupilumab, tralokinumab, lebrikizumab, nemolizumab) and Janus kinase inhibitors (JAKis) (baricitinib, upadacitinib, and abrocitinib). The vision that certain well-defined phenotypes and endotypes, as well as personal preferences, may guide the future treatment of AD is both tempting and appealing, but not yet reality. The accessibility of new drugs such as biologics and small molecules has opened up the discussion regarding personalized medicine, referring to the complex nature of AD as well as the experiences from clinical trials and real-world evidence. We have now reached the point of creating new strategies and AD treatment goals by increasing the amount of new information concerning the efficacy and safety of new drugs. This article has reviewed the novel treatment options for AD in the light of the heterogeneity of this disease and proposes a broader vision on the strategy of personalized treatment of AD.

Keywords: JAK inhibitors; atopic dermatitis; monoclonal antibodies.

Figure 1

Physiological mechanisms of action of several cytokines important in AD pathophysiology, which activate Janus kinases (JAKs) to phosphorylate signal transducers and transcription activators (STATs), have been illustrated. Two pathways, one activated by interleukin-4 and interleukin-13 mostly promoting inflammation and the second stimulated by other cytokines predominantly promoting pruritus, have been shown. Both biological and small molecule inhibitor drugs may block distinct pathways according to their specific place of action—narrower for biologics (dupilumab, tralokinumab, lebrikizumab, nemolizumab) and wider for JAK inhibitors (JAKi) (abrocitinib, upadacitinib, baricitinib).

Figure 2

A comprehensive view of the personalized therapy of atopic dermatitis is needed. In this model we propose five main factors to be taken into consideration in order to create a patient-tailored approach: patient’s preferences, real-life challenges and finding reasonable solutions of dealing with them, fast recognition and prevention of adverse effects, phenotypes and endotypes, and lastly, biomarkers, which are not yet available.