Upadacitinib works in select ankylosing spondylitis patients

The Janus kinase inhibitor upadacitinib induces significantly higher response than placebo in ankylosing spondylitis patients with inadequate response to biological disease-modifying antirheumatic drugs (bDMARDs), without introducing new safety signals, according to data from a phase III trial.

The trial included 420 adults (mean age 42 years, 72 percent male) with active AS who met modified New York criteria and had an inadequate response to one or two bDMARDs (tumour necrosis factor [TNFi] or interleukin-17 [IL-17i] inhibitors). They were randomized to receive upadacitinib 15 mg (n=211) or placebo (n=209), administered orally once daily.

About three-fourths of patients had prior exposure to one TNFi (74 percent), 13 percent to one IL-17i, 8 percent to two TNFis, 5 percent to one TNFi and one IL-17i, and 0.5 percent to two IL-17is. Seventy-seven percent of patients discontinued prior bDMARD therapy due to lack of efficacy, whereas 30 percent did so because of intolerance. Approximately one-third of patients (31 percent) used conventional synthetic DMARDs at baseline.

The primary endpoint of Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14 occurred with significantly greater frequency in the upadacitinib vs placebo group (45 percent vs 18 percent; p<0.0001).

Furthermore, active treatment produced substantially greater improvements in all multiplicity-controlled secondary endpoints, as follows: 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 (p<0.0001 for all).

There were no reports of malignancy, major adverse cardiovascular events, venous thromboembolism, or deaths among upadacitinib-treated patients.