Leonieke J.J. van Mens, Marleen G.H. van de Sande, Silvia Menegatti, Sija Chen, Iris C.J. Blijdorp, Henriette M. de Jong, Inka A. Fluri, Talia E. Latuhihin, Arno W.R. van Kuijk, Lars Rogge, Nataliya G. Yeremenko, Dominique L.P. Baeten.
Therapeutic options beyond TNF inhibition for psoriasis, psoriatic arthritis, and ankylosing spondylitis are narrowing towards the IL-17 cytokine pathway. Indeed, in psoriatic arthritis, IL-17A blocker has demonstrated superior efficacy compared to the TNF inhibitors. Spondyloarthritis, which covers both ankylosing spondylitis and psoriatic arthritis diseases, has not been well studied in regards to the IL-17 blocker, secukinumab. This study, sponsored by Novartis Pharma, examined the effect of secukinumab on immunopathology of the synovial membrane and systematic immune responses.
Twenty patients clinically diagnosed with peripheral spondyloarthritis received secukinumab (300mg once a week for 4 weeks and then once every 4 weeks thereafter) for 12 weeks. At various time points, clinical assessments, immuno-histological analysis of the synovial tissue, and systemic immune responses using Myriad RBM’s TruCulture blood collection and culturing system were conducted. At baseline, day 3, and 12 weeks post-therapy, whole blood was drawn into TruCulture tubes supplemented with zymosan for innate immunity activation, staphylococcal enterotoxin for T cell activation, or no stimulants (unstimulated).
At the completion of the 12 week study, 13 out of 20 patients achieved an ACR50 and ACR70 response, which is associated with a significant decrease in all clinical assessment parameters, including DAS28, CRP, and ESR. Histopathology analysis of the synovial tissue inflammation demonstrated a significant decrease of neutrophils and macrophage infiltration and decreases in message expression of inflammatory mediators (IL-17A, IL-6, MMP-3, and CCL20). In the table below (data extrapolated from the paper), analysis of systemic immune responses (TruCulture samples) using Myriad RBM HumanMAP A and B demonstrated that while there was targeted decrease in IL-17 and MMP-3 from stimulated T cells (SEB stimulated samples), there was no generalized decrease in T cell responses, as IFN-γ and TNF-α production remained unchanged.
This study demonstrated that secukinumab was able to improve synovial immunopathology in spondyloarthritis patients by targeting the IL-17 pathway, and that this affected systemic responses of the IL-17 pathway, but not other T cell activation pathways. Pairing of Myriad RBM TruCulture and HumanMAP tools, clinical studies can assess a subject’s systemic leukocyte population immune responses under immune targeted treatment conditions.