COPENHAGEN – The Janus kinase (JAK) inhibitor upadacitinib (Rinvoq, AbbVie) was associated with significant improvements in disease activity, pain, function, and quality of life, compared with placebo, in patients with nonradiographic axial spondyloarthritis (nr-axSpA), results of the first efficacy analysis of the phase 3, randomized SELECT-AXIS-2 trial showed.
The trial met its primary endpoint of an improvement of Assessment of SpondyloArthritis International Society 40% (ASAS 40) response criteria in the prespecified efficacy analysis at week 14, reported Filip Van den Bosch, MD, PhD, Ghent (Belgium) University.
Dr. Filip Van den Bosch
In all, 45% of patients randomized to receive upadacitinib achieved an ASAS 40, compared with 23% of those assigned to placebo (P < .001).
“This is the first study showing efficacy and showing that the JAK inhibitor upadacitinib might be a therapeutic option in patients with active, nonradiographic spondyloarthritis,” Van den Bosch said at the annual European Congress of Rheumatology.
Although JAK inhibitors have previously been shown to be efficacious and safe for the treatment of ankylosing spondylitis, the SELECT-AXIS-2 trial is the first to evaluate a JAK inhibitor in nonradiographic axSpA, he added.
Study details
Patients 18 years and older with rheumatologist-diagnosed nr-axSpA were eligible for the study if they also met 2009 ASAS classification criteria for axSpA but not 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-sensitivity C-reactive protein above the upper limit of normal (2.87 mg/L) at screening; and had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and patient-assessment of total back pain scores of 4 or greater based on a 0-10 numeric rating scale at study entry.
Patients were screened with MRI imaging of the spine and x-rays of the sacroiliac joints and spine, and then randomized to receive either placebo (157 patients) or upadacitinib 15 mg daily (158 patients) for 52 weeks. At the end of 52 weeks, all patients on upadacitinib will continue on the drug at the same dose level, and those assigned to placebo will be switched over to 15 mg upadacitinib daily maintenance.
As well as meeting the primary endpoint at week 14, response rates with the JAK inhibitor were higher at all time points over this initial time period, Dr. Van den Bosch noted.
Most targets hit
Of 14 multiplicity-controlled secondary endpoints, 12 were statistically better with upadacitinib, including change from baseline in patient’s assessment of total back pain, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Disease Activity Score, Low Disease Activity, Ankylosing Spondylitis Quality of Life, and MRI Spondyloarthritis Research Consortium of Canada score for sacroiliac joints.
Only the BASDAI and Maastricht Ankylosing Spondylitis Enthesitis Score were not significantly better with the JAK inhibitor.
The safety of upadacitinib in this setting was consistent with its known safety profile, Dr. Van den Bosch said.
Approximately half of all patients in each trial arm had an adverse event. Serious adverse events were reported in four patients assigned to upadacitinib versus two on placebo, and serious adverse events requiring drug discontinuation occurred in two and four patients, respectively.