Upadacitinib (ABT-494) is a Janus kinase 1 inhibitor that is being developed by AbbVie for the treatment of Crohn’s disease, ulcerative colitis, atopic dermatitis, psoriatic arthritis, axial SpAgiant cell arteritis, Takayasu arteritis, and ankylosing spondylitis (AS).

The EU and U.S. approved upadacitinib in 2019 under the brand name Rinvoq to treat rheumatoid arthritis (RA).

How does upadacitinib work?

AS is a progressive inflammatory autoimmune disease that affects the joints of the spine. As the disease advances, calcium deposits form where ligaments attach to the bones of the spine. This leads to reduced flexibility of the back.

Janus kinase (JAK) inhibitors, also known as jakinibs, are disease-modifying treatments that target the JAK enzymes. These enzymes are found inside cells and play important roles in cytokine signaling.

Many immune system diseases are related to abnormal production of cytokines, a group of proteins that help communication between cells. For example, a cytokine called interleukin-2 (IL-2) stimulates the production of T-cells, a specialized type of immune cell. After a cytokine binds to its receptor, JAKs contribute to the processes within the cell to produce an immune or inflammatory response. Therefore, JAK inhibitors may play an important role in autoimmune diseases such as AS, as they suppress immune responses.

Upadacitinib in clinical trials

Researchers evaluated the pharmacokinetics (basically, what the body does to a drug), safety, and tolerability of upadacitinib in a Phase 1 clinical trial (NCT01741493) in healthy volunteers and people with RA.

The results of the study supported further research of the potential therapy in Phase 2 trials in RA (NCT02720523 and NCT02049138), Crohn’s disease (NCT02782663 and NCT02365649), ulcerative colitis (NCT02819635), and atopic dermatitis (NCT02925117). Researchers are also testing the compound in a number of Phase 3 trials.

A multicenter, randomized, double-blind, placebo-controlled Phase 2b/3 study (NCT03178487) is also underway to evaluate upadacitinib’s safety and effectiveness in people with active AS. Researchers estimate the study will be completed by November 2020.

Other details

The most common adverse events of upadacitinib are headache, nausea, and upper respiratory and urinary tract infections.

 

Last updated: Aug. 31, 2020

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