FDA Approves Upadacitinib for Active Non-Radiographic Axial Spondyloarthritis

The US Food and Drug Administration (FDA) has approved once-daily oral 15 mg upadacitinib (RINVOQ) for the the treatment of adults with difficult-to-treat active non-radiographic axial spondyloarthritis (nr-axSpA).

The indication granted to AbbVie makes the JAK inhibitor the first of its drug class approved for both nr-axSpA and active anyklosing spondylitis (AS), and marks its sixth FDA indication across inflammatory diseases.

As a selective JAK inhibitor, upadacitinib has been evidenced to positively treat and is indicated for rheumatoid arthritis, psoriatic arthritis, AS, and active ulcerative colitis. It is similarly being considered for treatment of chronic immune-mediated inflammatory diseases including plaque psoriasis and Crohn’s disease.

The FDA’s latest approval for upadacitinib was supported by findings from the pivotal phase 3 SELECT-AXIS 2 clinical, in which the daily oral agent assessed for efficacy, safety and tolerability in adults with active nr-axSpA.

Investigators of the randomized, placebo-controlled, double-blind trial compared upadacitinib to placebo on outcomes including reduction of selected components of the AS Disease Activity Score (ASAS) composite index, an infinite-item scale gauging disease activity from none (0) to any level of disease severity. Components observed from the index included patient total back pain, patient global assessment (PGA) of disease activity, morning stiffness, and physical function. The team measured ASAS40 response as a patients improvement of disease activity by ≥40% from baseline.

Investigators additionally sought multiplicity-controlled endpoints including total back pain and Bath Ankylosing Spondylitis Disease Activity Index (BASFI).

At 14 weeks, the team observed a significantly greater mean decrease in total back pain from baseline among those treated with upadacitinib versus placebo, as well as significantly greater improvement in physical function per BASFI.

Nearly half of all patients in the upadacitinib arm achieved ASAS40 response at week 14 (44.9%), versus just 22.3% of the placebo arm.

Investigators observed a similar safety profile for upadacitinib in SELECT-AXIS 2 as was observed in clinical trials assessing patients with rheumatoid arthritis, psoriatic arthritis, and AS.

In a statement accompanying the approval, lead investigator Atul Deodhar, MD, professor of medicine and medical director of the Rheumatology Clinics for the Division of Arhtirits and Rheumatic Diseases at Oregon Health & Science University, called the FDA’s newest indication for the JAK inhibitor offers “ an important new therapeutic option for patients and their caregivers to help take control of their symptoms and disease."

“Many patients living with nr-axSpA continue to experience symptoms and are unable to control disease with current treatments,” Deodhar said. “In the SELECT-AXIS 2 trials, RINVOQ demonstrated efficacy in both nr-axSpA and AS with safety that was consistent across indications.”