SELECT-AXIS: 64-week results of upadacitinib in active ankylosing spondylitis

Upadacitinib demonstrated lasting efficacy and no new safety issues in patients with active ankylosing spondylitis (AS). The 64-week results of the open-label extension phase of the SELECT-AXIS 1 phase 2/3 trial showed that this JAK inhibitor could help to address an unmet need in active AS patients [1].

The SELECT-AXIS 1 trial (NCT03178487) included 187 adult patients with active AS (defined as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4 and back pain ≥4 on a numeric rating scale), who were naïve to biologic (b)DMARDs and had an inadequate response to NSAIDs at baseline. Patients were randomised to placebo (n=94, mean age 43.7) or 15 mg oral, once-daily upadacitinib (n=93, mean age 47.0). Previously presented primary results demonstrated that upadacitinib was efficacious and well tolerated at 14 weeks of treatment [2].

The trial continued with a 90-week open-label extension period that enrolled 178 patients from the randomisation period. The current interim analysis reported efficacy and safety data of upadacitinib through 64 weeks and was presented by Dr Atul Deodhar (Oregon Health & Science University, OR, USA). A non-responder imputation (NRI) approach was used for the analysis.

The results showed that 72% of the patients who continued upadacitinib after the randomisation period achieved an Assessment in SpondyloArthritis International Society 40% (ASAS40) at week 64 (see Figure). In comparison, primary results after 14 weeks in SELECT-AXIS 1 demonstrated that 51.6% of participants had reached ASAS40 versus 25.5% of the placebo group. From the patients switching from placebo to upadacitinib in the open-label extension period, 70% reached ASAS40 after 64 weeks.

Figure: Efficacy of upadacitinib versus placebo over 1 year as measured by ASAS40 [1]



ASAS40, Assessment in SpondyloArthritis International Society 40%; AO, as observed; NRI, non-responder imputation; QD, once daily.

Secondary efficacy outcome measures demonstrated efficacy of upadacitinib as well in this interim analysis. This was measured by the BASDAI 50% response, which was 67% for those switching from placebo at week 14 versus 70% for those continuing on upadacitinib. Furthermore, Patient Global Assessment (PGA) change from baseline was -4.41 (switching from placebo) versus -4.44 (continued upadacitinib), and the Bath Ankylosing Spondylitis Functional Index (BASFI) change from baseline was -3.39 versus -3.53, respectively.

No new safety issues emerged from this analysis. Adverse events were reported 618 times; 14 were considered serious. No cases of serious infection, active tuberculosis, venous thromboembolic events, major cardiovascular events, gastrointestinal perforation, inflammatory bowel disease, renal dysfunction, or death were reported following upadacitinib treatment. Creatine phosphokinase elevation occurred in 28 cases. However, these cases were mostly asymptomatic and transient. None of the cases led to discontinuation of the study. Herpes zoster was diagnosed in 5 patients. Dr Deodhar argued that herpes zoster infections are a recurring problem in JAK inhibitor recipients. Therefore, vaccination against this virus in advance of upadacitinib treatment should be considered. This could especially be beneficial for older patients, who are at higher risk of a herpes zoster infection.

1. Deodhar A, et al. Efficacy and Safety of Upadacitinib in Patients with Active Ankylosing Spondylitis: 1-Year Results from a Randomized, Double-blind Placebo-controlled Study With Open-label Extension. OP0144, EULAR 2021 Virtual Congress, 2–5 June.
2. Van der Heijde D, et al. 2019;394(10214):2108-17.

 

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Posted on 2 August 202117 May 2024