Systemic secukinumab treatment in patients with ankylosing spondylitis: the relationship between systemic and tear proinflammatory cytokines and ocular surface findings-a pilot study.

Backgrounds: Dry eye disease (DED) is a very common ocular surface disease that affects millions of people around the world. When we look at the pathogenesis of the disease, it is seen that inflammation plays a role. Ankylosing spondylitis (AS) is the prototype of immune-mediated inflammatory rheumatoid diseases in the spectrum of axial spondyloarthropathies. In studies, many proinflammatory cytokines (TNF-α, IL-23, IFN-γ), especially IL-17, have been shown in the etiopathogenesis of AS. Recently, anti IL-17 receptor inhibitors (secukinumab) have been using. It selectively binds to the IL-17 receptor, preventing its association with the target receptor. From this point of view, it was aimed to evaluate the blood and tear proinflammatory cytokine levels and ocular surface parameters of the patients treated with secukinumab, before and during the treatment.

Methods: This cross-sectional study included 12 patients with AS and 12 healthy individuals. The ocular surface and tear film were assessed using the Ocular Surface Disease Index (OSDI) questionnaire, tear film break-up time (TBUT), ocular surface staining, and Schirmer II test. The blood and tear samples were taken simultaneously. Signs and symptoms of DED were evaluated on the treatment day and 4 weeks, and 12 weeks after treatment. Tear and blood samples were taken once at the beginning of the study for the control group. Proinflammatory cytokine levels from collected tear and venous blood samples were examined in Pediatric Immunology laboratory. The tear levels of 30 cytokines were examined. Analyses were made with SPSS 25.0 package program.

Results: Compared to controls, AS patients had higher OSDI (p = 0.01), similar corneal staining with fluorescein and lissamine green (p = 0.12), and lower TBUT (p = 0.04). OSDI were found to be significantly different in the AS group at the measurement times (p = 0.01). IL-1B, IL-10, IL-13, IL-6, IL-12/IL-23p40, Rantes, Eotaxin, IL-17A, MIP-1A, GM-CSF, MIP-1B, MCP-1, IL-15, IL-5, IFN-G, IFN-A, TNF-A, IL-2, IL-7, IP-10, IL-2R, MIG, IL-4, and IL-8 levels in the AS serum and tears group did not differ at the first and third months (p > 0.05). IL-1RA measurements showed a significant decrease in the first and third months compared to baseline in the AS serum and tears (p = 0.04).

Conclusions: The findings of this study showed that there was decreased IL-1RA in patients with AS after secukinumab treatment in tears and serum. Interestingly, lachrymal IL-17 levels were similar but not statistical significant changes with two ocular parameters TBUT and Schirmer's test, suggesting a pathological role of IL-17 in rheumatological diseases. The results suggest that the inhibition of IL-1RA obtained by systemic administration of secukinumab but does not influence the severity of DED. Key Points • Many proinflammatory cytokines (TNF-α, IL-23, IFN-γ), especially IL-17, have been shown in the etiopathogenesis of ankylosing spondylitis. • IL1 affects the local lymfoid nodes and IL 17 affects the lacrimal gland. IL-17 and its receptor are very important structures for the pathogenesis of inflammation. • Secukinumab is a monoclonal antibody that neutralize the IL 1β and IL 17 A. • The findings of this study showed that there was decreased IL-1RA in patients with ankylosing spondylitis after secukinumab treatment in tears and serum.