Time to lift the moratorium on IL-23 inhibitors for axial psoriatic arthritis

Area of Science:

• Rheumatology
• Immunology
• Clinical Trials

Background:

• Expert panels recommend against IL-23 inhibitors for axial psoriatic arthritis (PsA) based on axial spondyloarthritis (axSpA) trial failures.
• However, data suggest potential benefits of IL-23 inhibitors in axial PsA.

Purpose of the Study:

• To examine clinical, microanatomical, and immunological differences between axSpA and axial PsA.
• To propose reconsidering the moratorium on IL-23 inhibitors for specific axial PsA phenotypes.

Main Methods:

• Review of post-hoc analyses from clinical trials of IL-23 inhibitors (ustekinumab, guselkumab, risankizumab) in axial PsA.
• Analysis of real-world evidence on spinal pain, outcome measures, and inflammation.
• Examination of data on C-reactive protein reduction and MRI scores in ankylosing spondylitis.
• Evaluation of response to biological therapies in relation to MRI-determined bone marrow oedema.

Main Results:

• Post-hoc analyses and real-world evidence demonstrate clinical improvements in axial PsA with IL-23 inhibitors.
• IL-23 inhibition showed C-reactive protein reductions and some MRI score improvements in ankylosing spondylitis.
• Divergent pathophysiological processes suggested by differential responses to biological therapies in axSpA.

Conclusions:

• Clinical, microanatomical, and immunological differences between axSpA and axial PsA indicate distinct IL-23 pathway dependence.
• Current recommendations against IL-23 inhibitors in axial PsA may be unwarranted.
• Reconsideration of IL-23 inhibitors, especially for HLA-B27 negative axial PsA, could expand therapeutic options.