The selective and reversible Janus kinase inhibitor upadacitinib (Rinvoq) significantly improved symptoms in adults with either ankylosing spondylitis (AS) or nonradiographic axial spondyloarthritis (nr-axSpA) when compared with placebo in a pair of studies from the phase 3 SELECT-AXIS 2 clinical trial, according to press releases issued Oct. 7 by manufacturer AbbVie.
Upadacitinib is currently approved in the European Union for patients with active AS, as well as patients with moderate to severe active rheumatoid arthritis and active psoriatic arthritis. Upadacitinib is approved by the Food and Drug Administration for adults with moderately to severely active RA, but is not currently approved for active AS or nr-axSpA.
In study 1, significantly more patients with AS who were randomly assigned to upadacitinib 15 mg once daily met the primary endpoint of 40% improvement in Assessment in Spondyloarthritis International Society (ASAS 40) response criteria at week 14, compared with placebo (45% vs. 18%) after 14 weeks (P < .0001).
The study of 420 patients with an inadequate response to biologic disease-modifying antirheumatic drug therapy gave half upadacitinib for 104 weeks and the other half placebo for 14 weeks, followed by upadacitinib for 90 weeks.
Patients treated with upadacitinib showed significant improvements in secondary endpoints of back pain, inflammation, physical function, and disease activity at week 14, compared with placebo.
Significantly more upadacitinib- than placebo-treated patients reached low disease activity on the AS Disease Activity Score (ASDAS) (44% vs. 10%). Upadacitinib also led to significantly greater improvements from baseline than did placebo on MRI Spondyloarthritis Research Consortium of Canada (SPARCC) Score for Spine, Patient’s Assessment of Total Back Pain, and Bath AS Functional Index (BASFI) score (–2.26 vs. –1.09).
COVID-19 and headache were the most common adverse events that were seen with upadacitinib during the first 14 weeks of the study (occurring in 3% or more). No adverse events led to study discontinuation among patients taking upadacitinib, compared with 1.4% on placebo, and serious adverse events were reported in 2.8% taking upadacitinib and in 0.5% on placebo. Serious infections with upadacitinib included four cases of COVID-19 and one case of uveitis.
Study 2 in patients with nr-axSpA
Study 2, which included 313 adults with nr-axSpA, yielded results similar to those of study 1 on the primary endpoint of meeting ASAS40 response criteria at week 14 (45% with upadacitinib 15 mg once daily vs. 23% with placebo; P < .0001), as well as on a variety of secondary efficacy endpoints and safety data.
Significantly better responses were observed at week 14 with upadacitinib for rate of low disease activity according to ASDAS (42% vs. 18%), changes in MRI SPARCC Scores for SI joints (–2.49 vs. 0.57), Patient’s Assessment of Total Back Pain (-2.91 vs. -2.00), and physical function based on the BASFI (–2.61 vs. –1.47).
The most common adverse events at 14 weeks, occurring in at least 3% of patients taking upadacitinib, included headache, COVID-19, nasopharyngitis, and nausea. Adverse events leading to study discontinuation occurred in 2.6% with upadacitinib and 1.3% with placebo; serious adverse events occurred in 2.6% and 1.3%, respectively.
Serious infections included COVID-19-induced pneumonia and pyelonephritis in patients taking upadacitinib and one case of hemorrhagic fever with renal syndrome with placebo.
The full results of the SELECT-AXIS 2 trial will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal, according to AbbVie.