JAKi for nonradiographic axSpA Save

One area of continued interest for many rheumatologists is the field of non-radiographic axial spondyloarthritis. Furthermore, the question of the utility of JAK inhibitors for the treatment of axial spondyloarthritis has been on the rise. 

Now, abstract OP0016, a phase 3 double blind, randomized, placebo-controlled trial by Dr. Deodhar’s group called the SELECT-AXIS 2 trial has demonstrated efficacy and safety of upadacitinib in patients with non-radiographic axSpA. 

These nr-axSpA patients fulfilled 2009 ASAS classification criteria for axSpA but did not meet the radiologic criterion of modified New York criteria, had objective signs of active inflammation consistent with axSpA on MRI of the sacroiliac joints, and/or high CRP levels. 313 patients received 15mg UPA daily or placebo for 52 weeks. The primary endpoint was ASAS40 at week 14. 

Patients receiving UPA had a significantly higher ASAS40 at week 14 when compared to placebo (45% vs. 23%). There were also improvements in pain, function and quality of life in patients taking UPA. Serious adverse effects leading to discontinuation was reported in 4 patients treated with UPA and 2 patients treated with placebo. 2 UPA patients had serious infections/zoster and 1 patient developed uveitis. There were no incidences of malignancy other than non-melanoma skin cancer, MACE, VTEs, IBD, death. 

In a world with growing but still limited therapeutic options, patients with nr-axSpA would benefit from a new therapeutic option with promising efficacy results along with no new risks identified. This data could set the ground for consideration of upadacitinib to treat nr-axSpA in the future. Perhaps this could also cause us to reconsider the safety profile of JAK inhibitors as a whole.