Rheumatoid arthritis (RA) is a chronic inflammatory disease primarily affecting 
the joints and is associated with significant levels of disability and reduced 
quality of life. Janus kinase (JAK) inhibitors are a relatively new class of 
small molecule oral treatments and offer an alternative for patients with RA who 
do not respond to conventional or biologic therapy. Upadacitinib is a JAK 
inhibitor engineered to be selective for JAK1, and has recently been approved 
for use in patients with moderate-to-severe RA. The purpose of this article is 
to provide a comprehensive review of upadacitinib, including preclinical 
development and characterization, phase I and II studies, and the phase III 
SELECT program. Ongoing trials of upadacitinib in additional indications, 
including spondyloarthritis, inflammatory bowel disease, and atopic dermatitis, 
are also discussed.