Secukinumab 150 mg effective in reducing NSAID dependence for ankylosing spondylitis: ASTRUM study breakthrough

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In a significant development for ankylosing spondylitis (AS) treatment, the phase IV ASTRUM study has demonstrated the efficacy and NSAID-sparing effect of secukinumab 150 mg. Published in Therapeutic Advances in Musculoskeletal Disease, the study involved 211 adult patients with active radiographic axial spondylarthritis (r-axSpA) and a BASDAI score of 4 or higher, who had inadequate responses to at least two NSAIDs. Patients were randomly assigned to receive secukinumab 150 mg at week 0, week 4, or week 16. 

The findings revealed that secukinumab significantly reduced NSAID reliance, with a week 12 ASAS20 response rate of 51.1% for the combined week 0 and week 4 groups, compared to 44.3% for the week 16 group. Although not statistically significant, this indicated a positive trend. More patients in the earlier treatment groups achieved ASAS40 and BASDAI50 milestones, showing greater improvements in disease activity and functional status by week 16. Additionally, more patients in these groups were able to discontinue NSAID use, underscoring the NSAID-sparing effect of secukinumab. 

 The MEASURE 2, 3, and 4 phase III trials reveal that secukinumab provides a sustained, long-term NSAID-sparing effect in patients with radiographic axial spondyloarthritis (r-axSpA) over four years. Results showed significant reductions in NSAID use, with more patients achieving a 50% reduction and an ASAS-NSAID score below 10. Additionally, a higher percentage of patients experienced clinically relevant improvements (BASDAI ≤2) with lower ASAS-NSAID scores. This highlights secukinumab’s efficacy in reducing NSAID dependence while managing r-axSpA symptoms. 

Interleukin-17A (IL-17A), a member of the IL-17 family, is a cytokine involved in normal inflammatory and immune responses. IL-17A has been shown to play an important role in the pathogenesis of AS. Indeed, studies have demonstrated increased numbers of IL-17A-producing cells in the circulation and the subchondral bone marrow of joints in patients with AS. Secukinumab (Cosentyx®), a pioneering fully human monoclonal antibody of the IgG1/κ isotype, is designed to target IL-17A and is approved for treating AS in the USA and the EU. By binding selectively to IL-17A, secukinumab inhibits its interaction with the IL-17 receptor, thus blocking the release of pro-inflammatory cytokines and chemokines. IL-17A is crucial in AS pathogenesis as it promotes inflammation and bone remodeling. Secukinumab’s inhibition of IL-17A reduces the production of these inflammatory mediators, decreasing neutrophil recruitment and activation, which in turn diminishes inflammation. This dual action on inflammation and bone remodeling underscores secukinumab’s efficacy in managing AS. 

 The ASTRUM study extends its clinical relevance to ankylosing spondylitis, offering a new treatment avenue for patients struggling with inadequate NSAID responses. The ability of secukinumab to reduce NSAID dependence is particularly noteworthy, as long-term NSAID use is associated with significant side effects. These findings underscore the potential of secukinumab to improve patient outcomes in AS by not only alleviating symptoms but also minimizing the need for NSAIDs. Further research and longer-term studies could consolidate its role in the therapeutic landscape of AS. As more patients gain access to this innovative treatment, the quality of life for those battling AS is set to improve, paving the way for a new standard in AS management. 

 References 

  1. Kiltz U, Baraliakos X, Brandt-Jürgens J, Wagner U, Lieb S, Sieder C, et al. Efficacy and NSAID-sparing effect of secukinumab 150 mg in ankylosing spondylitis: results from phase IV ASTRUM study. Ther Adv Musculoskelet Dis. 2024;16:1759720X241255486.  
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