Upadacitinib efficacious in patients with ankylosing spondylitis refractory to biologics
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Upadacitinib is efficacious over 14 weeks in patients with ankylosing spondylitis who mounted poor responses to biologic disease-modifying antirheumatic drugs, according to data published in the Annals of the Rheumatic Diseases.
“Overall, treatment options for [axial spondyloarthritis] remain limited compared with other rheumatic diseases such as rheumatoid arthritis (RA) or psoriatic arthritis (PsA), also given that conventional synthetic DMARDs or long-term corticosteroids are ineffective for treating axial symptoms,” Desiree van der Heijde, MD, PhD, of Leiden University Medical Center, in the Netherlands, and co-authors wrote. “To date, no dedicated studies of [JAK inhibitors (JAKi)] treatment in an AS population with an inadequate response (IR) to [biologic DMARD (bDMARD)] therapy have been conducted.”
To investigate the efficacy of upadacitinib (Rinvoq, AbbVie) 15 mg in patients who mounted poor responses to biologic DMARDs, van der Heijde and colleagues conducted SELECT-AXIS 2, a randomized, double-blind, parallel-group, placebo-controlled study. The trial consisted of a 35-day screening period and a 14-week trial period. Patients were eligible for enrollment if they were aged 18 years or older with a confirmed AS diagnosis.
Enrolled patients had active disease at screening and baseline, defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score, and a patient assessment of back pain, of four or greater on a scale of zero to 10. In addition, included patients demonstrated a poor response to two or more NSAIDs and biologic DMARDs.
Visits occurred at weeks 1, 2, 4, 8, 12 and 14, with MRIs conducted on the spine and sacroiliac joints at baseline and at 14 weeks. MRIs were analyzed by two readers with no knowledge of treatment plans or time points. Patients were randomized 1:1 to receive either upadacitinib 15 mg or a placebo.
The primary endpoint for the trial was Assessment in SpondyloArthritis International Society 40 (ASAS40) at week 14. Secondary endpoints included changes from baseline in Ankylosing Spondylitis Disease Activity Score based on CRP and Spondyloarthritis Research Consortium of Canada MRI spine inflammation score. Treatment-emergent adverse events were defined as adverse events that emerged following the first dose and prior to the dose at week 14.
A total of 420 patients with active AS were included in the analysis. According to the researchers, significantly more patients who received upadacitinib 15 mg (45%) than placebo (18%) achieved ASAS40 at week 14 (P < .0001). Additionally, statistically significant improvements in all multiplicity-controlled secondary endpoints were seen in patients who received upadacitinib, compared with patients who received placebo therapy (P < .0001). Although 41% of patients receiving upadacitinib reported adverse events, compared with 37% of patients in the placebo group, there were no reports or findings of malignancy, major cardiovascular events, venous thromboembolism or deaths in the test group.
“Upadacitinib 15 mg significantly improved the signs and symptoms of active AS and was well tolerated for 14 weeks of treatment in bDMARD-IR patients, consistent with results observed in the upadacitinib AS bDMARD-naïve study,” van der Heijde and colleagues. “Upadacitinib 15 mg offers an effective treatment option for bDMARD-naïve and bDMARD-IR patients with active AS.”
Perspective
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The SELECT-AXIS 2 study is the first to evaluate the efficacy and safety of upadacitinib, a select Janus Kinase inhibitor, in patients with active ankylosing spondylitis who have had inadequate response to one or more biologic disease-modifying antirheumatic drugs (bDMARDS).
The primary endpoint of ASAS40 at 14 weeks was significantly higher among patients given 15 mg of upadactinib than those receiving placebo, at 45% vs. 18%, respectively (P < .0001). These findings are similar to the SELCT-AXIS 1 study, which enrolled biologic naïve patients and achieved a 51% ASAS40. There was also significant improvement across the secondary endpoints of BASFI, ASDS and MRI-graded sacroiliac inflammation.
This study required prior bDMARD exposure, with 73% of patients in the active treatment arm having a previous inadequate response to tumor necrosis factor inhibitors (TNFi), while 14% of patients had previous exposure to Interleukin-17 inhibitors (IL-17i), and only 4% demonstrated incomplete response to both TNFi and IL-17i.
Rheumatologists welcome additional therapeutics for active ankylosing spondylitis. We would also encourage studies to compare the efficacy of JAK inhibition to current biologic therapies, as well as the efficacy in treating coexisting extra-articular manifestations of disease, such as uveitis and inflammatory bowel disease.
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