JAK inhibition with upadacitinib works well in nr-axSpA

Treatment with upadacitinib improves disease activity, pain, function, and quality of life (QoL) in patients with non-radiographic axial spondyloarthritis (nr-axSpA) in a study touted as the first to evaluate a Janus kinase (JAK) inhibitor for this condition.

In this double-blind, randomized, placebo-controlled phase III SELECT-AXIS 2 trial, significantly more nr-axSpA patients on upadacitinib achieved the primary endpoint of improvement in ASAS40* at week 14 vs those on placebo (45 percent vs 23 percent; p<0.0001). [EULAR 2022, abstract OP0016]

Additionally, 12 of 14 multiplicity-controlled secondary endpoints were significantly better with upadacitinib vs placebo (p<0.01) based on several outcome measures such as a change from baseline in total back pain, Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score (ASDAS) Low Disease Activity, Ankylosing Spondylitis Quality of Life (ASQoL), and Spondyloarthritis Research Consortium of Canada (SPARCC) score for sacroiliac joint (SI) inflammation on magnetic resonance imaging (MRI).

“Ours is the first study to demonstrate the efficacy of upadacitinib in active nr-axSpA,” SELECT-AXIS 2 investigator Dr Filip Van den Bosch from Ghent University Hospital in Gent, Belgium told an audience of rheumatologists at EULAR 2022. “This highlights the potential of upadacitinib to help counter inflammation, relieve pain, and improve function, enabling patients with nr-axSpA to take control of their disease.”

An important first step

Nr-axSpA is a progressive and disabling inflammatory disease mainly affecting the spine and the sacroiliac joints – it has clinical signs and symptoms of SpA, but without the characteristic radiographic changes on X-rays. “It has very limited treatment options,” shared Van den Bosch. “The disease often affects young adults, causing spinal inflammation that leads to back pain and stiffness.”

Dr Fabian Proft, head of the clinical trials unit at Charite University Hospital, Berlin, Germany, and co-moderator of the oral abstract session where Van den Bosch presented results of the SELECT-AXIS-2 trial, said the efficacy of upadacitinib has been proven in radiographic axSpA. “But this is the first data on JAK inhibition in nr-axSpA, hence this is an important step.”

Enrolled in the trial were 313 patients aged 18 years and older with nr-axSpA, who had signs of active inflammation consistent with axSpA on MRI, and/or a high sensitivity C-reactive protein (CRP) higher than 2.87 mg/L at screening. Patients also had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and total spinal pain scores of ≥4 (on a 0–10 numeric rating scale) at baseline.

After an MRI of the spine and X-rays of the SI joints and spine were performed, patients were randomly assigned in a 1:1 ratio to receive oral upadacitinib 15 mg daily or a placebo for 52 weeks.

At 14 weeks of treatment, adverse events were reported in 48 percent and 46 percent of patients in the upadacitinib and placebo arms, respectively.  There were no deaths or major adverse cardiovascular events reported. No new safety risks were observed compared to the known safety profile of upadacitinib.

“The results support the potential use of upadacitinib in patients with active nr-axSpA,” said Van den Bosch, adding that the future for improving the lives of patients with nr-axSpA is promising.