JAK inhibitor shows to be effective in non-radiographic axSpA

Once-daily therapy with upadacitinib led to an Assessment of SpondyloArthritis International Society 40 (ASAS40) response in 45% of patients with active, non-radiographic axial spondylarthritis (nr-axSpA) at week 14 in the SELECT-AXIS-2 trial. This was the first phase 3 trial data of JAK inhibitors ever presented in this indication.

Both TNF blockers and IL-17 blockers have shown to be effective in nr-axSpA. “But of course, there are patients that primarily fail these treatments, and sometimes patients respond well and lose response later or they can develop toxicity. So, 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) who presented the first efficacy analysis of the phase 3, randomised SELECT-AXIS-2 trial (NCT04169373) [1].

Adults with a clinical diagnosis of nr-axSpA who also fulfilled the 2009 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 a biologic disease-modifying antirheumatic drug (DMARD; i.e. TNF blockers or IL-17 inhibitors) and all participants 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.

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   1. 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, 1-4 June, Copenhagen, Denmark.

 

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Posted on 7 June, 20227 June, 2022