Using bespoke IL-23/IL-17A and IL-17F axis gene cards to Gain Clues into Understanding Synovial Mechanisms of Refractory Psoriatic Arthritis

Start date: 11 October 2023
End date: 10 October 2024
Value: £218,818.48
Partners and collaborators: Department of Medical and Biological Sciences, Rheumatology Clinic, University of Udine, Italy.
Primary investigator: Professor Dennis McGonagle
Co-investigators: Miss Nicole McDermott, Dr Mark Harland, Dr Chi Wong, Dr Tom Macleod
External co-investigators: Alen Zabotti

Description

Funder: UCB (Union Chimique Belge) Biopharmaceutical

Strong genetic, experimental and clinical evidence implicates the IL-23/IL-17 axis in the pathogenesis of psoriatic arthritis (PsA). Both IL-17A inhibition and dual inhibition with IL-17A and IL-17F with bimekizumab has shown efficacy in PsA. However, bimekizumab showed particularly robust and high responses in subjects who previously failed a TNF inhibitor thus opening a translational window of insight into the potential role of IL-17F in refractory or difficult to treat synovitis in PsA. At present, however, little is known about the cellular sources, magnitude of elevation and cell interactome of IL-17F in PsA synovitis. In this work we will evaluate PsA synovial tissue from TNF responders (n =20) and non-responders (n=15) to test the hypothesis that there is dysregulated IL-17A and IL-17F in TNF responsive and TNF refractory PsA synovial tissue. Tissue from RA will serve as a control including early RA (n=10) and TNF treatment refractory RA (n= 10). We will extract RNA from FFPE tissue and perform a bespoke gene card including IL-17F, IL17A, IL-23 and TNF transcripts as well as members of the downstream NF-κB pathway and relevant chemokine transcripts including CCR6 and CCL20. This one year extension to our existing collaboration will provide data that might support the use of bimekizumab in TNF refractory PsA and a platform for further research.

Impact

Forecasted to support the use of bimekizumab in TNF refractory PsA