The selective Janus kinase 1 (JAK1) inhibitor updacitinib, which was approved in 2019 for use in patients with rheumatoid arthritis (RA), is also showing promise as a treatment for ankylosing spondylitis (AS). In the SELECT-AXIS 1 study, upadacitinib not only improved the signs and symptoms of AS, but also reduced inflammation in the spine and sacroiliac joints on MRI.

The study follows trials of upadacitinib in RA and also encouraging phase II trials of other JAK inhibitors in AS. SELECT-AXIS 1 enrolled adult patients with active AS who had not yet been treated with biologic DMARDs. A dose of 15 mg updacitinib orally once daily was chosen for evaluation.

At week 14 of SELECT-AXIS 1, 52% (48 of 93) of the patients treated with upadacitinib achieved an ASAS40 response (indicating ≥40% improvement from baseline according to Assessment of SpondyloArthritis International Society criteria), compared with 26% (24 of 94) of patients who were treated with placebo. Differences between the two groups in ASAS40 response were apparent as early as week 2 and sustained through 14 weeks.

As well as the primary endpoint of ASAS40 response, the study also met several secondary endpoints related to disease activity (including partial remission), the degree of functional limitation and MRI-detected axial inflammation. Updacitinib was well-tolerated, with a safety profile consistent with that seen in previous studies in RA. Rates of adverse events were similar in the treatment and placebo groups and no new safety concerns were apparent.

Long-term efficacy and safety data are expected to be collected in the ongoing extension period of SELECT-AXIS 1. Further studies are also needed to evaluate upadacitinib in patients with AS who have previously failed to respond to biologic DMARD therapy, as well as in the full spectrum of axial spondyloarthritis.