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<h3>Background and Importance</h3> Interleukin-17A (IL-17A) is a key cytokine in the pathogenesis of immune-mediated diseases such as psoriasis, psoriatic arthritis, and axial spondyloarthritis. Secukinumab, a fully human IgG1κ antibody, and ixekizumab, a humanised IgG4 antibody, both neutralise IL-17A. Molecular differences may influence immunogenicity and persistence, supporting real-world studies of long-term outcomes. <h3>Aim and Objectives</h3> To describe and compare treatment persistence and reasons for discontinuation of secukinumab and ixekizumab across all indications used in a regional hospital. <h3>Material and Methods</h3> A retrospective review included patients treated with secukinumab or ixekizumab from January 2017 to September 2025. Collected data included age, sex, indication, treatment duration, and discontinuation reasons. Persistence was defined as a gap >90 days. <h3>Results</h3> A total of 194 patients were included: 100 on secukinumab and 94 on ixekizumab. Indications were plaque psoriasis (n=80; 28/52), psoriatic arthritis (n=71; 41/30), and axial spondyloarthritis (n=43; 31/12). Median age was 49.7 years (10–79.3), 46.4% male. Median treatment duration was 24.3 months for secukinumab and 24.5 months for ixekizumab. Persistence at 12 months was 62% and 49%, and at 24 months 33% and 37.2%, respectively. Discontinuations occurred in 68 secukinumab patients (seven toxicity, 44 lack of efficacy, six patient decision, five pregnancy) and 37 ixekizumab patients (seven toxicity, 17 loss of response, one patient decision, three relocation, two comorbidities). Both were well tolerated, with mostly mild adverse events (upper respiratory infections, injection site reactions). <h3>Conclusion and Relevance</h3> In this real-world retrospective study, secukinumab and ixekizumab showed comparable persistence rates at 12 months and acceptable long-term safety across all indications. Although persistence decreased over time, both agents maintained similar patterns of discontinuation, mainly due to lack of efficacy, mild adverse events, or patient-related reasons. Overall, IL-17A inhibitors demonstrated sustained tolerability and adherence in clinical practice, supporting their continued use in the management of immune-mediated inflammatory diseases. <h3>References and/or Acknowledgements</h3> 1. Agencia Española de Medicamentos y Productos Sanitarios (AEMPS). Technical details of Cosentyx (secukinumab). Available in: CIMA. Accessed 8 October 2025. Agencia Española de Medicamentos y Productos Sanitarios (AEMPS). Technical details of Taltz (ixekizumab). Available in: CIMA. Accessed 8 October 2025. <h3>Conflict of Interest</h3> No conflict of interest