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Full 1-year results have now been published for the pivotal SELECT-AXIS 2 trial that underpinned the FDA approval of upadacitinib (Rinvoq) for non-radiographic axial spondyloarthritis (axSpA), demonstrating sustained efficacy and reasonable safety.

Symptom improvement of at least 40% by Assessment of SpondyloArthritis International Society criteria (ASAS40) was achieved in 63% of patients randomized to the drug, a Janus-associated kinase (JAK) inhibitor, after 1 year on treatment versus 43% of the placebo group in the 259-patient study (P<0.001), according to Filip Van den Bosch, MD, of Ghent University in Belgium, and colleagues.

Inactive disease was achieved in 33% of those on upadacitinib, compared with 11% of patients assigned to placebo, the researchers .

"Treatment with upadacitinib was generally safe and well tolerated, and no new safety risks were identified," Van den Bosch and colleagues wrote. "These longer-term results continue to support the favorable benefit-risk profile of upadacitinib 15 mg once daily in patients with active [non-radiographic] axSpA, including those who are treatment refractory."

The drug was for the non-radiographic axSpA indication on the basis of results after 14 weeks of treatment. At that point, ASAS40 had been achieved by 45% of patients receiving the active agent versus 22% of the placebo group. The condition differs from radiographic SpA -- also called ankylosing spondylitis -- in that non-radiographic axSpA comes with less structural damage as determined from imaging.

With last May's approval for Crohn's disease, upadacitinib now , including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and atopic dermatitis.

Numerous other outcomes, both for efficacy and safety, were tracked for the study's full 12 months, including Axial Spondyloarthritis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index, C-reactive protein (CRP) level, and patient-reported back pain severity.

For all but high-sensitivity CRP readings, the proportion of patients achieving certain degrees of improvement, such as ASDAS low disease activity (LDA) and inactive disease, increased from week 14 to the final 1-year evaluation. For example, ASDAS LDA was met by about 50% of patients on upadacitinib at week 14, rising to almost 70% at 1 year. Similar improvements with time were also seen in the placebo group, but the differences in response rates remained significant throughout. CRP declined quickly, in just the first 2 weeks of treatment, and remained at about the same low level for the remainder of the treatment period.

Study Details

Patients in the had a mean age of 42 and a mean symptom duration of 9 years. Some 60% were white. Participants were randomized 1:1 to upadacitinib or placebo, given orally once daily.

Mean baseline values were as follows, for the upadacitinib and placebo groups, respectively:

• ASAS Health Index: 9.4 and 9.5
• ASDAS: 3.6 and 3.7
• Total back pain (10-point scale): 7.2 and 7.3
• High-sensitivity CRP at screening: 13.6 and 10.5 mg/dL
• Presence of enthesitis: 80% in both groups

Van den Bosch and colleagues reported that so-called declined by a mean 3.2 points with the active drug versus 2.1 points with placebo at 1 year (P<0.001).

Similar proportions of treatment-emergent adverse events were seen in the two study arms: 69% with upadacitinib and 66% with placebo. A few more patients in the upadacitinib group discontinued because of such events (six versus four), and certain types of events were more common with the drug:

• Overall infections: 68 vs 60
• Herpes zoster infections: 5 vs 1
• Neutropenia: 8 vs 1

Other events of interest, such as malignancies and liver abnormalities, were rare and didn't differ between groups. One potential safety signal was that mean alanine and aspartate aminotransferase levels were somewhat higher with upadacitinib and rose continually as treatment continued. But the investigators noted that no grade 3 or higher increases occurred, and no one discontinued on account of lab abnormalities.

An open-label 1-year extension is part of SELECT-AXIS 2; results have not yet been reported.

Limitations to the trial, the researchers said, included the lack of an active comparator and small numbers of patients in some subgroups. Radiographic progression was not evaluated. Also, 20 patients in the placebo group and 16 taking upadacitinib, who had completed 14 weeks of treatment, discontinued before reaching the 1-year mark.

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