A novel oral treatment possibility for non-radiographic axSpA on the horizon

Although both TNF blockers and cytokine blockers have shown to be effective in spondyloarthritis, there is an ongoing demand for other treatment modalities. In the SELECT-AXIS 2 trial, once-daily oral therapy with upadacitinib showed to be markedly effective and well-tolerated in patients with active, non-radiographic axial spondyloarthritis (nr-axSpA) at week 14.

The JAK pathway is a potential therapeutic target in spondyloarthritis and could become an effective new oral treatment. Previously, upadacitinib has shown its efficacy and safety in the phase 2/3 SELECT-AXIS 1 trial (NCT03178489), which evaluated the JAK inhibitor in biologic-naïve participants with active ankylosing spondylitis [1]. Both TNF blockers and IL-17 blockers have shown to be effective in nr-axSpA. “Having another mode of action, and not directly against a single cytokine but an inflammatory pathway, might be useful,” said Prof. Filip van den Bosch (Ghent University, Belgium) [2].

The SELECT-AXIS 2 trial (NCT04169373) was separated into 2 studies according to whether participants had ankylosing spondylitis with an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARDs) or nr-axSpA with objective signs of inflammation. Prof. van den Bosch presented the study part including participants with nr-axSpA: adults with a clinical diagnosis of nr-axSpA who also fulfilled the 2009 Assessment of SpondyloArthritis International Society (ASAS) classification criteria were treated with upadacitinib 15 mg once daily (n=157) or placebo (n=157). “According to a central reading, participants did not meet the radiologic criterion of modified New York criteria but had signs of active disease, namely elevated C-reactive protein concentrations or sacroiliitis in MRI,” Prof. van den Bosch explained. About a third of participants were previously treated with bDMARDs (i.e. TNF blockers or IL-17 inhibitors), and all had shown an inadequate response to ≥2 non-steroidal anti-inflammatory drugs (NSAIDs).

After 14 weeks, 45% of participants randomised to receive upadacitinib achieved the primary endpoint (i.e. ASAS40 response) compared with 23% of those assigned to placebo (P<0.0001). “I have 3 take-home messages here:  there was a clear difference between upadacitinib and placebo, the absolute difference is in the ballpark of other biologics (around 40% and 50%), and, lastly, we saw a fast response with a separation of curves already at week 2,” Prof. van den Bosch commented.

Upadacitinib was also superior in many other multiplicity-controlled secondary endpoints, including change from baseline in patient's assessment of total back pain, Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Quality of Life (ASQoL), and MRI Spondyloarthritis Research Consortium of Canada (SPARCC) score for sacroiliac joint inflammation.

Overall, the safety profile of upadacitinib was consistent with what has been observed with other inflammatory musculoskeletal diseases, and no new risks were identified. Adverse events were reported in 48% and 46% of participants in the upadacitinib and placebo arms, respectively. No deaths or major adverse cardiovascular events were observed during 14 weeks of treatment with the JAK inhibitor.

Similar efficacy in ankylosing spondylitis patients

The results of the second part of the SELECT AXIS 2 study, including 420 participants with ankylosing spondylitis, were revealed in a poster tour presentation by Prof. Désirée van der Heijde (Leiden University Medical Center, the Netherlands) [3]. “This is the first clinical trial to assess the efficacy and safety of a JAK inhibitor in an active ankylosing spondylitis population with an inadequate response to bDMARDs,” Prof. van der Heijde emphasised.

Significantly more participants achieved the primary endpoint of ASAS40 response at week 14 with upadacitinib versus placebo (45% vs 18%; P<0.0001). The onset of effect was already noted at week 4. Moreover, all secondary endpoints met statistical significance in favour of upadacitinib across multiple clinical domains of ankylosing spondylitis, e.g. ASDAS, BASFI, and sacroiliac joint inflammation on MRI [3].

Treatment-emergent adverse events from baseline to week 14 were similar in the upadacitinib and placebo arms (41% compared with 37% in the placebo group), and there were no new safety signals.

1. Deodhar A, et al. Arthritis Rheumatol. 2022;74:70–80.
2. Deodhar A, et al. Efficacy and safety of upadacitinib in patients with active non-radiographic axial spondyloarthritis: a double-blind, randomized, placebo-controlled phase 3 trial. OP0016, EULAR 2022 Congress, 1–4 June, Copenhagen, Denmark.
3. Van der Heijde D, et al. Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis refractory to biologic therapy: a double-blind, randomized, placebo-controlled phase 3 trial. POS0306, EULAR 2022 Congress, 1–4 June, Copenhagen, Denmark.

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Posted on 21 July 202217 May 2024