INTRODUCTION
Janus kinase (JAK) proteins are key, evolutionarily conserved mediators of external-to-internal cellular signaling, activated when external cytokines bind to their respective transmembrane receptors, triggering phosphorylation of JAK proteins, then STAT proteins, inside the cell. Dysregulated signaling through JAK1 and JAK2 has been implicated in various inflammatory-driven cutaneous conditions, including atopic dermatitis (AD) and vitiligo.1 Both topical and oral JAK inhibitors have been developed and continue to be explored for these diseases, aiming to modulate these crucial immune pathways. Oral JAK inhibitors offer systemic control for more severe cases, while topical formulations provide localized treatment with minimal systemic absorption, reducing the potential for side effects.
All JAK kinase domain inhibitors used for treating chronic inflammatory conditions have received a "boxed warning." The boxed warning encompasses 4 safety risk categories: (1) serious infections, (2) malignancies, (3) major adverse cardiovascular events (MACE), and (4) thromboembolic events (ie, deep vein thrombosis (DVT), pulmonary emboli (PE), and arterial thrombosis).2 This warning was derived from the Oral Surveillance study, a post-marketing trial evaluating tofacitinib in rheumatoid arthritis patients 50 years of age and older and at least one additional cardiovascular risk factor,, with concomitant methotrexate use, which revealed increased risks of MACE, malignancies, and death compared to tumor necrosis factor (TNF) inhibitors.3 These findings prompted the FDA to extend its boxed warning to all JAK inhibitors with a similar mechanism of action to tofacitinib,
All JAK kinase domain inhibitors used for treating chronic inflammatory conditions have received a "boxed warning." The boxed warning encompasses 4 safety risk categories: (1) serious infections, (2) malignancies, (3) major adverse cardiovascular events (MACE), and (4) thromboembolic events (ie, deep vein thrombosis (DVT), pulmonary emboli (PE), and arterial thrombosis).2 This warning was derived from the Oral Surveillance study, a post-marketing trial evaluating tofacitinib in rheumatoid arthritis patients 50 years of age and older and at least one additional cardiovascular risk factor,, with concomitant methotrexate use, which revealed increased risks of MACE, malignancies, and death compared to tumor necrosis factor (TNF) inhibitors.3 These findings prompted the FDA to extend its boxed warning to all JAK inhibitors with a similar mechanism of action to tofacitinib,
