Introduction Long-term safety and efficacy of upadacitinib in patients with active ankylosing spondylitis (AS) has not been previously reported. Methods In SELECT-AXIS 1, patients receiving placebo... Show moreIntroduction Long-term safety and efficacy of upadacitinib in patients with active ankylosing spondylitis (AS) has not been previously reported. Methods In SELECT-AXIS 1, patients receiving placebo were switched to upadacitinib 15 mg once daily at week 14 while patients initially randomised to upadacitinib continued their regimen through week 104. Efficacy was assessed using as-observed (AO) and non-responder imputation (NRI). Results Of 187 patients randomised, 144 patients (77%) completed week 104. Among patients receiving continuous upadacitinib, 85.9% (AO) and 65.6% (NRI) achieved Assessment of SpondyloArthritis international Society 40 response (ASAS40) at week 104. Similar magnitude of ASAS40 responses were observed among patients who switched from placebo to upadacitinib (88.7% and 63.8%, respectively). The mean change from baseline to week 104 in Spondyloarthritis Research Consortium of Canada MRI spine and sacroiliac joint inflammation scores were -7.3 and -5.3, respectively, in the continuous upadacitinib group and -7.9 and -4.9 in the placebo-to-upadacitinib switch group. The mean (95% CI) change from baseline to week 104 in the modified Stoke Ankylosing Spondylitis Spine Score was 0.7 (0.3, 1.1) in the total group. Adverse event rate was 242.7/100 patient-years. No serious infections, adjudicated major adverse cardiovascular events, lymphoma, non-melanoma skin cancer, or gastrointestinal perforations were observed. Conclusions Upadacitinib 15 mg once daily showed sustained and consistent efficacy over 2 years for ASAS40 and other clinically relevant endpoints. A low rate of radiographic progression was observed and no new safety findings were observed. Show less
Deodhar, A.; Heijde, D. van der; Sieper, J.; Bosch, F. van den; Maksymowych, W.P.; Kim, T.H.; ... ; Song, I.H. 2021
Objective To report the efficacy and safety of upadacitinib through 1 year in patients with ankylosing spondylitis (AS). Methods In the SELECT-AXIS 1 study, adults with active AS and an inadequate... Show moreObjective To report the efficacy and safety of upadacitinib through 1 year in patients with ankylosing spondylitis (AS). Methods In the SELECT-AXIS 1 study, adults with active AS and an inadequate response to nonsteroidal antiinflammatory drugs were randomized to receive upadacitinib 15 mg once daily or placebo. At week 14, patients who had been randomized to receive placebo were switched to upadacitinib, and all patients continued in the open-label extension and received upadacitinib up to week 104; interim data up to week 64 are reported herein. Results Of 187 patients, 178 completed week 14 on study drug and entered the open-label extension. Similar proportions of patients in either group (continuous upadacitinib or placebo-to-upadacitinib) achieved Assessment of SpondyloArthritis international Society 40% response (ASAS40) or Ankylosing Spondylitis Disease Activity Score (ASDAS) showing low disease activity at week 64: >= 70% of patients achieved these end points based on nonresponder imputation (NRI) and >= 81% based on as-observed analyses. Furthermore, >= 34% (NRI) and >= 39% (as-observed analysis) achieved ASDAS showing inactive disease or ASAS showing partial remission at week 64. Mean changes from baseline (week 0) to week 64 in pain, function, and inflammation showed consistent improvement or sustained maintenance through the study. Among 182 patients receiving upadacitinib (237.6 patient-years), 618 adverse events (260.1 per 100 patient-years) were reported. No serious infections, major adverse cardiovascular events, venous thromboembolic events, gastrointestinal perforation, or deaths were reported. Conclusion Upadacitinib 15 mg once daily showed sustained and consistent efficacy over 1 year. Patients who switched from placebo to upadacitinib at week 14 showed similar efficacy versus those who received continuous upadacitinib. Show less
Deodhar, A.; Heijde, D. van der; Gensler, L.S.; Kim, T.H.; Maksymowych, W.P.; Ostergaard, M.; ... ; Coast-X Study Grp 2020
Background The JAK pathway is a potential therapeutic target in ankylosing spondylitis. This study assessed the efficacy and safety of upadacitinib, a selective JAK1 inhibitor, in patients with... Show moreBackground The JAK pathway is a potential therapeutic target in ankylosing spondylitis. This study assessed the efficacy and safety of upadacitinib, a selective JAK1 inhibitor, in patients with ankylosing spondylitis.Methods This multicentre, randomised, double-blind, placebo-controlled, two-period, parallel-group, phase 2/3 study, SELECT-AXIS 1, enrolled adults in 62 sites in 20 countries. Eligible patients had active ankylosing spondylitis, fulfilled modified New York criteria, were previously untreated with biological disease-modifying antirheumatic drugs, and had inadequate response to at least two or intolerance or contraindication to non-steroidal anti-inflammatory drugs. Patients were randomly assigned 1:1 using interactive response technology to take oral upadacitinib 15 mg once daily or oral placebo for the 14-week period 1; only period 1 data are reported here. The primary endpoint was the composite outcome measure of the Assessment of SpondyloArthritis international Society 40 response at week 14. Analyses were done in the full analysis set of patients who were randomly assigned and received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03178487.Findings Between Nov 30, 2017, and Oct 15, 2018, 187 patients were randomly assigned to upadacitinib 15 mg (93 patients) or to placebo (94 patients), and 178 (95%) patients (89 in the upadacitinib group and 89 in the placebo group) completed period 1 on study drug (by the completion date of Jan 21, 2019). Significantly more patients had an Assessment of SpondyloArthritis international Society 40 response in the upadacitinib group versus in the placebo group at week 14 (48 [52%] of 93 patients vs 24 [26%] of 94 patients; p=0.0003; treatment difference 26% [95% CI 13-40]). Adverse events were reported in 58 (62%) of 93 patients in the upadacitinib group versus 52 (55%) of 94 in the placebo group. The most common adverse event in the upadacitinib group was increased creatine phosphokinase (eight [9%] of 93 patients in the upadacitinib group vs two [2%] of 94 patients with placebo). No serious infections, herpes zoster, malignancy, venous thromboembolic events, or deaths were reported; one serious adverse event was reported in each group.Interpretation Upadacitinib 15 mg was efficacious and well tolerated in patients with active ankylosing spondylitis who had an inadequate response or contraindication to non-steroidal anti-inflammatory drugs. These data support the further investigation of upadacitinib for the treatment of axial spondyloarthritis. Copyright (C) 2019 Elsevier Ltd. All rights reserved. Show less
Kishimoto, M.; Yoshida, K.; Ichikawa, N.; Inoue, H.; Kaneko, Y.; Kawasaki, T.; ... ; Tomita, T. 2019
