Axial spondyloarthritis: Moving beyond cytokine based therapies to cellular targets and advanced therapeutics

Rheumatology as a specialty is moving past cytokine inhibitors which have dominated the therapeutic landscape since the turn of the century, with novel cell-targeting therapies emerging to treat immune-mediated multisystem inflammatory diseases such as systemic lupus, systemic sclerosis, small vessel vasculitides, and inflammatory myositis. Like many inflammatory arthritides, axial spondyloarthritis (axSpA) therapeutics has been limited to either inhibitors of TNF and IL-17, or blocking intracellular signaling of cytokines through Janus Kinase inhibitors. This systematic review chronicles the clinical progress made in the field of selective T cell depleting agents, the potential for novel cellular targeting therapies using Chimeric Antigen Receptor - T (CAR-T) therapy, as well the challenges posed by this approach for treatment of axSpA. A review of the MEDLINE, OVID and clinicaltrials.gov databases was performed which revealed no ongoing or completed open label or completed registered clinical trials. However recent data have highlighted potential for selective CD8⁺ T cell targets with proof of concept using a monoclonal antibody against TRBV9+ CD8⁺ T cells from a published case study and one randomized placebo-controlled trial, as well as other emerging therapeutics that are shifting focus from cytokine-based therapeutics to T cell targeting agents. In this review, we identified emerging therapeutic platforms of cellular immunotherapy, potential therapeutic targets, and discuss potential adverse effects related to cell-targeting therapies. While at present there is a dearth of clinical data on cellular targeting treatment options in axSpA, ongoing investigations into the pathogenesis of axSpA and identification of new molecular targets may help facilitate opportunities to develop CAR-T and other cell-based therapies for treatment of axSpA.