From bench to bedside - is there a role of IL-17 drugs in rheumatoid arthritis?

Abstract

ABSTRACT Introduction IL-17 has been described as a pro-inflammatory cytokine that is relevant in the seronegative spondylarthritides with IL-17 targeted therapies being licensed for their treatment. There is evidence to demonstrate that IL-17 is found in RA joints and contributes to the pro-inflammatory cascade. This results in synovial hyperplasia and osteoclastogenesis thus causing joint destruction and bony erosions. Areas covered This review article summarizes trials that have studied the use of IL-17 targeted therapies in RA patients who have failed conventional synthetic disease-modifying therapy (C-DMARDS) and biologic DMARDS. Expert opinion The trials that have studied IL-17 inhibitors in RA patients have only shown a modest improvement in disease activity. In several trials, the primary endpoint was not achieved whilst in others, when comparing with existing licensed biologics for RA, did not demonstrate any superiority. Tissue Necrosis Factor-alpha (TNF-α) likely plays more of a pivotal role in the pathogenesis of RA with IL-17 having a synergistic effect. Therefore, in our opinion, IL-17 inhibitors as an independent therapy for RA are less likely to provide a cost-effective benefit. There may be scope to potentially combine it with TNF-α-inhibitors (TNF-i), but this requires further research especially with the potential concerns related to increased immunosuppression.