Efficacy and safety of upadacitinib for active ankylosing spondylitis refractory to biological therapy: A double-blind, randomised, placebo-controlled phase 3 trial

Désirée Van Der Heijde, Xenofon Baraliakos, Joachim Sieper, Atul Deodhar, Robert D. Inman, Hideto Kameda, Xiaofeng Zeng, Yunxia Sui, Xianwei Bu, Aileen L. Pangan, Peter Wung, In Ho Song

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: To evaluate the efficacy and safety of upadacitinib, a Janus kinase inhibitor, in patients with active ankylosing spondylitis (AS) with an inadequate response (IR) to biological disease-modifying antirheumatic drugs (bDMARDs). Methods: Adults with active AS who met modified New York criteria and had an IR to one or two bDMARDs (tumour necrosis factor or interleukin-17 inhibitors) were randomised 1:1 to oral upadacitinib 15 mg once daily or placebo. The primary endpoint was Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14. Sequentially tested secondary endpoints included Ankylosing Spondylitis Disease Activity score, Spondyloarthritis Research Consortium of Canada MRI spine inflammation score, total back pain, nocturnal back pain, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index and Maastricht Ankylosing Spondylitis Enthesitis Score. Results are reported from the 14-week double-blind treatment period. Results: A total of 420 patients with active AS were randomised (upadacitinib 15 mg, n=211; placebo, n=209). Significantly more patients achieved the primary endpoint of ASAS40 at week 14 with upadacitinib vs placebo (45% vs 18%; p<0.0001). Statistically significant improvements were observed with upadacitinib vs placebo for all multiplicity-controlled secondary endpoints (p<0.0001). Adverse events were reported for 41% of upadacitinib-Treated and 37% of placebo-Treated patients through week 14. No events of malignancy, major adverse cardiovascular events, venous thromboembolism or deaths were reported with upadacitinib. Conclusion: Upadacitinib 15 mg was significantly more effective than placebo over 14 weeks of treatment in bDMARD-IR patients with active AS. No new safety risks were identified with upadacitinib. Trial registration number: NCT04169373.

Original languageEnglish (US)
Article number2022-222608
JournalAnnals of the rheumatic diseases
DOIs
StateAccepted/In press - 2022

Keywords

  • antirheumatic agents
  • inflammation
  • Magnetic Resonance Imaging
  • spondylitis, ankylosing

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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