IL-23 and axial disease: do they come together?

Area of Science:

• Immunology
• Rheumatology
• Genetics

Background:

• Interleukin-23 (IL-23) is a critical cytokine implicated in the development of spondyloarthropathies like psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).
• IL-23 drives the overexpression of IL-17 through T helper 17 (Th17) cells and other immune cells, contributing to disease pathogenesis.
• Genetic studies, animal models, and human translational research confirm the significant role of IL-23 in these inflammatory conditions.

Purpose of the Study:

• To explore the role of IL-23 in various spondyloarthropathies.
• To investigate the efficacy of IL-23 inhibition across different spondylitis subtypes.
• To discuss potential reasons for conflicting clinical outcomes observed with IL-23 inhibitors.

Main Methods:

• Review of genetic associations and animal models.
• Analysis of translational studies in human subjects.
• Examination of clinical trial data for IL-23 inhibitors in psoriasis, PsA, and ankylosing spondylitis.

Main Results:

• IL-23 inhibition demonstrates clear benefits in psoriasis and peripheral PsA.
• Trials targeting IL-23 have shown limited success in treating ankylosing spondylitis.
• Preliminary data suggests potential benefit in axial PsA, warranting dedicated axSpA trials.

Conclusions:

• The efficacy of IL-23 inhibition varies across different spondylitis phenotypes.
• Further research is needed to confirm the therapeutic potential of IL-23 inhibitors in axial spondyloarthritis.
• Understanding the differential roles of IL-23 in distinct spondyloarthropathies is essential for targeted treatment strategies.