Upadacitinib 15 mg sustains efficacy through 1 year in ankylosing spondylitis
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Upadacitinib 15 mg demonstrates consistent, sustained efficacy in ankylosing spondylitis through year 1, according to data published in Arthritis & Rheumatology.
“Upadacitinib, a JAK inhibitor engineered for increased selectivity for JAK1 over JAK2, JAK3, and tyrosine kinase 2, was investigated for the treatment of patients with AS who had an inadequate response to NSAIDs in the randomized, placebo-controlled phase 2/3 SELECT-AXIS 1 study,” Atul Deodhar, MD, of Oregon Health & Science University, in Portland, and colleagues wrote.
“The study met its primary endpoint with a significantly greater proportion of patients receiving upadacitinib achieving Assessment of SpondyloArthritis international Society 40 (ASAS40) at week 14 versus placebo (51.6% for upadacitinib 15 mg once daily [QD] vs 25.5% for placebo; P<0.001), as well as several multiplicity-controlled secondary endpoints reflecting significant improvement in disease activity, function, and magnetic resonance imaging outcomes for upadacitinib versus placebo,” they added. “Upadacitinib was well tolerated, and no serious infections, herpes zoster, malignancy, venous thromboembolic events, or deaths were reported during the first 14 weeks.”
To assess the efficacy and safety of upadacitinib in patients with AS through 1 year, Deodhar and colleagues conducted an interim analysis of the SELECT-AXIS 1 extension study. In the initial trial, a total of 187 adults from 62 centers across 20 countries were randomized 1:1 to receive either 15 mg of daily upadacitinib or a placebo for 14 weeks. Participants who completed this first period were then eligible for the extension, in which patients received open-label upadacitinib 15 mg once daily for 90 weeks, up to week 104. For this analysis, Deodhar and colleagues reported on data up to week 64.
A total of 178 participants completed the first period and entered the open-label extension. Among these patients, 89 had received continuous upadacitinib and 89 had switched from placebo to the study drug. In all, 160 participants — including 78 who received continuous upadacitinib and 82 who switched from placebo — completed week 64. Safety through 1 year was based on available data with a cutoff date of Jan. 31, 2020.
According to the researchers, similar proportions of those in the continuous and switch groups achieved ASAS40 or Ankylosing Spondylitis Disease Activity Score (ASDAS) low-disease activity at week 64. Specifically, at least 70% of patients achieved these endpoints based on non-responder imputation, while 81% or more demonstrated them based on as-observed analyses. In addition, at least 34% of participants, based on non-responder imputation, and at least 39% in the as-observed analyses, achieved ASDAS inactive disease or ASAS partial remission at week 64.
Mean changes from baseline to week 64 in pain, function, and inflammation demonstrated consistent improvement or sustained maintenance through the study.
Regarding safety, there were a total of 618 adverse events reported among 182 patients who received upadacitinib across 237.6 patient-years, representing a rate of 260.1 per 100 patient-years. There were no reported serious infections, major adverse cardiovascular events, venous thromboembolic events, gastrointestinal perforation or deaths.
“Overall, oral upadacitinib therapy over 1 year was efficacious and well tolerated, suggesting it may help address an unmet need for patients with AS who have active disease and inadequate response to NSAIDs,” Deodhar and colleagues wrote. “The long-term efficacy and safety of upadacitinib, including long-term imaging, will be assessed over 2 years in the SELECT-AXIS 1 extension.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
We have come a long way in ankylosing spondylitis or spondyloarthritis since the limited treatment options of NSAIDs and sulfasalazine (off label for AS). We now have five TNF inhibitors — adalimumab, etanercept, certolizumab pegol, infliximab and golimumab — and two IL-17A inhibitors — secukinumab and ixekizumab — FDA-approved for AS.
From the results of this study, it appears we now have another medication, upadacitinib, that will work for AS. This study is impressive in that there were no serious adverse events at one year and the efficacy was significant. In fact, separation from placebo was significant at week 2. We have seen this early efficacy in rheumatoid arthritis, and it makes for a very satisfying follow-up visit for the patient and the doctor. The versality of the JAK inhibitors to control disease has been impressive.
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