POS0877 SECUKINUMAB UP-TITRATION IN PATIENTS WITH RADIOGRAPHIC AND NON-RADIOGRAPHIC AXIAL SPONDILOARTHRITIS: A MULTICENTER REAL WORLD SPANISH EXPERIENCE

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Background: Axial Spondyloarthritis (axSpA) is a chronic inflammatory disease of the axial skeleton, affecting about 1% globally, and characterized by inflammation and new bone formation. It includes radiographic (r-axSpA) and non-radiographic (nr-axSpA) stages. Management involves both pharmacological and non-pharmacological interventions, with recent advancements in therapies like TNFi, IL-17i, and JAKi. Secukinumab, an IL-17A inhibitor, has shown efficacy at 150 mg, with up-titration to 300 mg approved for severe cases. This study examines the real-world impact, retention, and safety of this dosage increase in Spain. Objectives: To evaluate the real-world efficacy, retention, and safety of secukinumab up-titration to 300 mg in axial spondyloarthritis (axSpA) patients, including radiographic (r-axSpA) and non-radiographic (nr-axSpA) subgroups, with partial response to 150 mg. Methods: This multicentre, retrospective, observational study conducted in rheumatology units across Spain from May 2017 to July 2023, included adults (≥18 years) diagnosed with r-axSpA or nr-axSpA following modified New York and/or ASAS criteria with partial response (ASDAS ≥2.1) after ≥3 months on 150 mg secukinumab, followed for up to 24 months. Outcomes included changes in disease activity (ASDAS) after dose escalation, treatment retention assessed using Kaplan-Meier analysis, and Cox regression explored factors associated with discontinuation. Safety was evaluated through adverse event (AE) incidence. Results: The study included 106 axSpA patients, with 77 (73%) having r-axSpA and 29 (27%) nr-axSpA. The follow-up period amounted 124 patient-years, concluding at the 24 months visit. The r-axSpA group had 66% males compared to 52% in the nr-axSpA group, with similar mean ages (48.98 vs. 45.72 years). Cardiovascular risk factors were comparable between groups. Uveitis (21% vs. 3%) and psoriasis (14% vs. 0%) were more common in r-axSpA. HLA-B27 positivity was higher in r-axSpA (79% vs. 59%). The median time from diagnosis to secukinumab initiation was 8.0 years for r-axSpA and 2.0 years for nr-axSpA, with similar prior treatment histories. Secukinumab up-titration to 300 mg significantly reduced ASDAS scores in both r-axSpA and nr-axSpA patients, especially within the first 6 months, with sustained improvements at 24 months. Median ASDAS decreased from 4.12 to 1.97 in r-axSpA and from 4.12 to 1.49 in nr-axSpA. The longitudinal mixed model (LMM) analysis confirmed consistent ASDAS-CRP reductions over time without significant differences between subgroups (Table 3). At 6 months, 87.79% of patients remained on therapy, with 59.07% continuing at 24 months (Figure 2). Kaplan-Meier analysis showed no significant difference in retention between r-axSpA and nr-axSpA (p=0.4). Cox regression analysis found no statistically significant factors associated with treatment discontinuation, although age and HLA-B27 positivity showed non-significant trends towards higher discontinuation rates. Over 95 patient-years, 15 adverse events (AEs) were reported, an incidence rate of 15.79 per 100 patient-years. The most common AEs were infections and cutaneous reactions (20% each), followed by elevated transaminase levels, mild leukopenia and neutropenia, and major cardiovascular events (6.7% each). Most treatments were continued, with only one permanent discontinuation. No new cases of uveitis, IBD, or psoriasis were noted. AEs were more frequent after six months post-escalation. Conclusion: These findings support secukinumab 300 mg as a safe, effective, and adaptable therapeutic option for axSpA patients with partial response to the standard dose. Tailored dosing strategies leveraging secukinumab's flexibility may improve disease management and outcomes in real-world settings. REFERENCES: [1] Sieper J, Poddubnyy D. Axial spondyloarthritis. The Lancet [Internet]. 2017 Jul;390(10089):73–84. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0140673616315914. [2] Khan S, Shridharmurthy D, Lapane KL, Dube C, Kay J, Yi E, et al. The disease burden of axial spondyloarthritis: through a gendered lens. Clin Rheumatol [Internet]. 2022 Apr;41(4):1115–24. Available from: http://www.ncbi.nlm.nih.gov/pubmed/34988682. [3] Fattorini F, Gentileschi S, Cigolini C, Terenzi R, Pata AP, Esti L, et al. Axial spondyloarthritis: one year in review 2023. Clin Exp Rheumatol [Internet]. 2023 Nov;41(11):2142–50. Available from: http://www.ncbi.nlm.nih.gov/pubmed/37965699. [4] Dean LE, Jones GT, MacDonald AG, Downham C, Sturrock RD, Macfarlane GJ. Global prevalence of ankylosing spondylitis. Rheumatology (Oxford) [Internet]. 2014 Apr;53(4):650–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24324212. [5] Navarro-Compán V, Sepriano A, El-Zorkany B, van der Heijde D. Axial spondyloarthritis. Ann Rheum Dis [Internet]. 2021 Dec;80(12):1511–21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/34615639. [6] Ivanova M, Zimba O, Dimitrov I, Angelov AK, Georgiev T. Axial Spondyloarthritis: an overview of the disease. Rheumatol Int [Internet]. 2024 Apr 30;44(9):1607–19. Available from: https://link.springer.com/10.1007/s00296-024-05601-9. Acknowledgements: NIL . Disclosure of Interests: None declared . © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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