The Janus kinases (JAK) are a group of molecules, composed of JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2), which are key components within the JAK-signal transducers and activators of transcription pathway, where cytokine receptor signaling takes place. These molecules play a foundational role in the underlying pathogenesis of multiple immune-related conditions such as atopic dermatitis (AD), rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, and others. Thus far, JAK inhibitors for inflammatory conditions have only been marketed for the treatment of rheumatoid arthritis and psoriatic arthritis, but ongoing phase II and phase III clinical trials for other immune-mediated diseases, such as AD, have also shown promising results. This review summarizes the clinical data available from various trials and reports on the safety and efficacy of abrocitinib, baricitinib, and upadacitinib, the three oral systemic JAK inhibitors used in the treatment of AD. The safety and efficacy of JAK inhibitors for the treatment of AD are emerging in the literature. It is important that dermatologists are aware of any potential adverse events or risks associated with the use of JAK inhibitors in order to promote a higher standard of treatment and quality of living.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by joint involvement, extra-articular manifestations, comorbidities, and increased mortality. In the last few decades, the management of RA has been dramatically improved by the introduction of a treat-to-target approach aiming to prevent joint damage progression. Moreover, the increasing knowledge about disease pathogenesis allowed the development of a new drug class of biologic agents targeted on immune cells and proinflammatory cytokines involved in RA network. Despite the introduction of several targeted drugs, a significant proportion of RA patients still fail to achieve the clinical target; so, more recently the focus of research has been shifted toward the inhibition of kinases involved in the transduction of the inflammatory signal into immune cells. In particular, two Janus kinase (JAK) inhibitors, baricitinib and tofacitinib, have been licensed for the treatment of RA as a consequence of a very favorable profile observed in randomized controlled trials (RCTs) conducted across different RA subpopulations. Both these new compounds are active on the majority of four JAK family members (JAK1, JAK2, JAK3, and TYK2), whereas the most recent emerging approach is directed toward the development of JAK1 selective inhibitors (upadacitinib and filgotinib) with the aim to improve the safety profile by minimizing the effects on JAK3 and, especially, JAK2. In this narrative review, we discuss the rationale for JAK inhibition in RA, with a special focus on the role of JAK1 selective blockade and a detailed description of available data from the results of clinical trials on upadacitinib and filgotinib.