Upadacitinib

Immune-mediated inflammatory diseases such as rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis are driven by multiple cytokines. Traditional biological agents only block a single cytokine. Therefore, there is still a need for new oral, broad-spectrum, and rapid-acting strategies in clinical practice.
Upadacitinib is a selective JAK1 inhibitor that competitively blocks the binding of ATP to JAK1, inhibiting the JAK-STAT signaling pathway, thereby down-regulating the transcription and release of key pro-inflammatory factors such as IL-6 and IL-7. Upadacitinib has a selectivity for JAK1 that is tens of times higher than that for JAK2/3/TYK2, and can precisely intervene in the core inflammatory process while preserving the functions of other JAKs. By precisely shutting down the inflammatory signaling hub of JAK1, Upadacitinib achieves rapid, potent, and long-lasting anti-inflammatory effects without completely shutting down the immune defense, providing a new targeted, single-drug approach that can achieve the standard of care for various immune-mediated diseases.
With its high selectivity for JAK1 inhibition, convenient oral administration, broad-spectrum indications, and rapid and durable efficacy, Upadacitinib has become the new benchmark for first-line targeted treatment of immune-inflammatory diseases.

Fig. 1 Upadacitinib's mechanism of action. (Mohamed M E F.; et al. 2024)

Xiong Z et al. developed and assessed an ethanol-based binary ethosomal carbomer hydrogel for topical delivery of upadacitinib (UPA) for psoriasis treatment.
The ethosomes were prepared by an alcohol-injection and sonication method, and the resulting vesicles were ~114 nm in size, with an entrapment and drug loading of 73.75 % and 21.16 %, respectively. The hydrogel significantly increased UPA permeation (2.3-fold) and intradermal retention (2.9-fold) compared with a conventional cream. Topical application of the formulation in vivo markedly improved skin phenotype and histopathology, significantly decreased TNF-α, IL-17 and IL-23 levels versus the model group, and caused no visible irritation.
In conclusion, the UPA-loaded ethosomal hydrogel represents a high-permeation, high-retention, potent anti-inflammatory and safe topical formulation for improved psoriasis management.

Fig. 2 Upadacitinib-loaded binary ethosomal hydrogel is used to improve psoriasis treatment. (Xiong Z.; et al. 2025)