Safety and Efficacy of Upadacitinib in Patients With Active Ankylosing Spondylitis and an Inadequate Response to Nonsteroidal Antiinflammatory Drug Therapy: One-Year Results of a Double-Blind, Placebo-Controlled Study and Open-Label Extension

Abstract

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 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.

Trial registration: ClinicalTrials.gov NCT03178487.

© 2021 AbbVie Inc. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.

Figures

Figure 1

Patient disposition through week 64. Among the reasons for study drug discontinuation in period 2, adverse events included diarrhea, headache, and vertigo in 1 patient; squamous cell carcinoma of the tongue in 1 patient; and headache in 1 patient in the continuous upadacitinib group; and hemiparesthesia (right side) and intervertebral disc protrusion in 1 patient in the placebo‐to‐upadacitinib group; patient withdrawals included 1 patient who did not wish to administer the medication (lost to follow‐up) and 1 patient who did not want to continue the study procedure or the study treatment in the placebo‐to‐upadacitinib group, and 1 patient who had challenges with transportation to the clinic in the continuous upadacitinib group; the “other” category included 1 patient who moved to a different country. mNY = modified New York; QD = once daily.

Figure 2

Percentage of patients achieving Assessment of SpondyloArthritis international Society 40% response (ASAS40) and ASAS showing partial remission (ASAS PR) over time. All patients randomized to receive placebo received open‐label upadacitinib beginning at week 14. 95% CI = 95% confidence interval; AO = as‐observed; NRI = nonresponder imputation; QD = once daily.

Figure 3

Percentage of patients achieving Ankylosing Spondylitis Disease Activity Score showing low disease activity (ASDAS LDA;

Figure 4

Change from baseline (Δ) in Ankylosing Spondylitis Disease Activity Score using the C‐reactive protein level (ASDAS‐CRP) and Bath Ankylosing Spondylitis Functional Index (BASFI) over time. All patients randomized to receive placebo received open‐label upadacitinib beginning at week 14. AO = as‐observed; MMRM = mixed‐effects model repeated measures; QD = once daily.

Figure 5

Change from baseline (Δ) in back pain and nocturnal back pain over time. All patients randomized to receive placebo received open‐label upadacitinib beginning at week 14. Evaluation of back pain was based on the question, “What is the amount of back pain that you experienced at any time during the last week?” and evaluation of nocturnal back pain was based on the question, “What is the amount of back pain at night that you experienced during the last week?” Both were scored on a numerical rating scale of 0–10. AO = as‐observed; MMRM = mixed‐effects model repeated measures; QD = once daily.