Real-World Italian Study Supports IL-17 Inhibitor Cycling in Psoriatic Arthritis

Key Clinical Summary

• A multicenter Italian real-world study of 868 patients with psoriatic arthritis found durable long-term retention of interleukin-17 (IL-17) inhibitors, with overall retention of 77.5% at 12 months and 52.1% at 36 months.

• Drug persistence did not differ significantly between IL-17 inhibitor-naïve and IL-17 inhibitor-experienced patients, supporting IL-17 inhibitor cycling after prior exposure.

• Male sex and previous IL-17 inhibitor use were associated with lower discontinuation risk, whereas axial disease, multiple prior biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), and more recent treatment initiation predicted shorter treatment retention.

Interleukin-17 (IL-17) inhibitors demonstrated sustained long-term treatment retention among patients with psoriatic arthritis (PsA), regardless of previous exposure to an IL-17 inhibitor, according to a multicenter real-world study published in Rheumatology and Therapy. The Italian investigation evaluated treatment persistence across routine clinical practice and provides additional evidence supporting IL-17 inhibitor cycling after prior therapy.

Study Findings

Investigators conducted a retrospective observational study involving 868 consecutive patients with PsA treated with an IL-17 inhibitor at 24 rheumatology centers throughout Italy. Most participants (89.3%) were IL-17 inhibitor-naïve, and the median patient age was 56 years.

The primary endpoint was treatment retention, evaluated using Kaplan-Meier survival analyses. Across the entire cohort, IL-17 inhibitor persistence remained high throughout follow-up, with retention rates of 90.7% at 6 months, 77.5% at 12 months, 60.9% at 24 months, and 52.1% at 36 months.

Among IL-17 inhibitor-naïve patients, retention rates reached 90.5%, 77.6%, 61.7%, and 53.9% at 6, 12, 24, and 36 months, respectively. Patients previously exposed to an IL-17 inhibitor demonstrated corresponding retention rates of 92.2%, 77.0%, 54.0%, and 33.9%.

Although treatment persistence appeared numerically lower among previously exposed patients at later time points, investigators found no statistically significant difference in overall drug retention between the two groups.

Multivariable Cox regression analyses identified several factors associated with treatment persistence. Male sex and prior IL-17 inhibitor exposure were associated with a lower risk of treatment discontinuation. In contrast, axial involvement, a greater number of previous b/tsDMARDs, and later calendar year of IL-17 inhibitor initiation were independently associated with reduced treatment retention.

The investigators concluded, “IL-17i showed high long-term retention in real-world PsA, with no significant difference between naïve and previously exposed patients.” They added that these findings “support the sustained effectiveness of IL-17i therapy.” Results suggest that previous IL-17 inhibitor exposure does not substantially compromise long-term treatment retention in routine rheumatology practice.

Clinical Implications

Treatment sequencing remains an important challenge in PsA management, particularly after inadequate response or discontinuation of biologic therapy. These real-world findings suggest that prior exposure to an IL-17 inhibitor should not necessarily discourage clinicians from considering another agent within the same therapeutic class.

Drug retention serves as an important real-world measure that reflects treatment effectiveness, tolerability, and patient adherence. The consistently high persistence observed through three years supports the durability of IL-17 inhibition in routine clinical practice.

The identification of factors associated with shorter retention—including axial disease and extensive prior biologic exposure—may help clinicians recognize patients who warrant closer monitoring or individualized treatment strategies. At the same time, the absence of a significant difference in persistence between IL-17 inhibitor-naïve and IL-17 inhibitor-experienced patients provides reassurance that IL-17 inhibitor cycling remains a reasonable therapeutic option when clinically appropriate.

The findings add real-world evidence supporting IL-17 inhibitor use across diverse PsA populations and suggest that cycling within the IL-17 inhibitor class may remain an effective treatment strategy after previous exposure. Further prospective studies may help clarify which patient subgroups derive the greatest long-term benefit from this approach.

Reference

Paci V, Ariani A, Celletti E, et al. Does prior exposure affect retention? A real-world, multicentre assessment of IL-17 inhibitor cycling in psoriatic arthritis. Rheumatol Ther. 2026;13(3):629-643. doi:10.1007/s40744-026-00839-0