# The Pathophysiological Significance of Dual Inhibition of IL-17A and IL-17F in Psoriatic Arthritis and Axial Spondyloarthritis

## TL;DR

This paper reviews how blocking both IL-17A and IL-17F could improve treatment for psoriatic arthritis and axial spondyloarthritis by targeting chronic inflammation.

## Contribution

The paper highlights the novel concept of dual inhibition of IL-17A and IL-17F as a promising therapeutic strategy for spondyloarthritis.

## Key findings

- Dual inhibition of IL-17A and IL-17F may address therapeutic escape and chronic inflammation in spondyloarthritis.
- Bimekizumab and emerging agents like sonelokimab show promise in treating difficult-to-manage SpA.
- Blocking both cytokines could lead to deeper and more sustained remission in patients.

## Abstract

Spondylarthritides (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) are immune-mediated diseases in which the IL-23/IL-17 axis plays a central role. IL-17A inhibition is already a well-established and effective treatment strategy. Emerging evidence suggests that IL-17F, a cytokine closely related to IL-17A but less potent, is not a passive bystander but a key participant in chronic sustained inflammation and therapeutic escape, offering a compelling concept for dual inhibition. This review aims to examine the pathophysiological significance of dual inhibition of IL-17A and IL-17F in psoriatic arthritis and axial spondyloarthritis.

Conducting a search through PubMed/MEDLINE, Scopus, and Web of Science, using keywords and Medical Subject Headings (MeSH) terms such as “spondyloarthritis”, “psoriatic arthritis”, “IL-17A”, “IL-17F”, “IL-23”, “IL-23 independent mechanisms”, “dual inhibition”, “pathogenesis”, “gut-joint axis”, “secukinumab”, “ixekizumab”, “bimekizumab”, “sonelokimab”, we select the relevant literature for this comprehensive pathophysiological narrative.

This review examines the distinct and synergistic functions of IL-17A and IL-17F in key tissues, including the synovium, enthesis, skin, gut, and eye, and their contribution to the paradoxical imbalance of bone remodelling. The advent of dual IL-17A/F inhibitors, particularly bimekizumab has revolutionised our therapeutic approach, offering a promising option for patients with difficult-to-treat SpA. We also discuss emerging technology agents, such as sonelokimab and izokibep.

Inhibiting both IL-17A and IL-17F signifies not only a significant therapeutic advancement but also a vital strategy towards overcoming the limitations of our current armamentarium in achieving deeper and more sustained remission in SpA. Future studies and long-term data will be essential in determining the position of dual IL-17A/F inhibitors within treatment guidelines.