Upadacitinib (AbbVie), a Janus kinase inhibitor, significantly improves the signs and symptoms of non-radiographic axial spondyloarthritis compared with placebo at 14 weeks, according to a recent trial. The findings, which were published in The Lancet by Atul Deodhar (Oregon Health and Science University, Portland, USA) et al, support the potential use of upadacitinib as a new therapeutic option for these patients, note the researchers.
While upadacitinib has been shown to be effective in patients with ankylosing spondylitis, the aim of this study was to assess the efficacy and safety of upadacitinib in non-radiographic axial spondyloarthritis patients, noted Deodhar et al.
The SELECT-AXIS 2 study is a multicentre, randomised, double-blind, placebo-controlled, phase three trial conducted at 113 sites across 23 countries—Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, France, Germany, Hungary, Israel, Japan, Mexico, Poland, Russia, Slovakia, South Korea, Spain, Taiwan, Turkey, Ukraine, and the USA.
Those eligible for the trial were adults who had active non-radiographic axial spondyloarthritis, with objective signs of inflammation based on magnetic resonance imaging (MRI) or elevated C-reactive protein and an inadequate response to non-steroidal anti-inflammatory drugs.
Patients were randomly assigned (1:1) to receive oral upadacitinib 15mg once daily or placebo using interactive response technology. Random treatment assignment was stratified by MRI inflammation in the sacroiliac joints and screening high-sensitivity C-reactive protein status (MRI-positive and C-reactive protein-positive, MRI-positive and C-reactive protein-negative, and MRI-negative and C-reactive protein-positive) and previous exposure to biologic disease-modifying antirheumatic drugs.
Treatment assignment was masked from patients, investigators, study site personnel, and the study sponsor (AbbVie). The primary endpoint was the proportion of patients with an Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14. Analyses were performed on the full analysis set of patients, who underwent random allocation and received at least one dose of study drug.
Between 26 November 2019 and 20 May 2021, 314 patients with active non-radiographic axial spondyloarthritis were enrolled into the study, and 313 received study drug (156 in the upadacitinib group and 157 in the placebo group). A total of 295 (94%) patients (145 in the upadacitinib group and 150 in the placebo group) received treatment for the full 14 weeks.
A significantly higher ASAS40 response rate was achieved with upadacitinib compared with placebo at week 14 (70 [45%] of 156 patients vs. 35 [23%] of 157 patients; p<0·0001; treatment difference 22%, 95% confidence interval [CI] 12–32).
In addition, the rate of adverse events up to week 14 was similar in the upadacitinib group (75 [48%] of 156 patients) and placebo group (72 [46%] of 157 patients). Serious adverse events and adverse events leading to discontinuation of study drug occurred in four (3%) of 156 patients in the upadacitinib group and two (1%) of 157 patients in the placebo group.
Few patients had serious infections or herpes zoster in either treatment group (each event occurred in two [1%] of 156 patients in the upadacitinib group and one [1%] of 157 patients in the placebo group). Five (3%) of 156 patients in the upadacitinib group had neutropenia; no events of neutropenia occurred in the placebo group.
Finally, no opportunistic infections, malignancies, major adverse cardiovascular events, venous thromboembolic events, or deaths were reported with upadacitinib treatment.