Anti-IL-23 Therapy Effective in Improving Axial Inflammation in PsA, But Not axSpA?

Authors of a viewpoint discuss the lack of efficacy of anti-IL-23 therapy for axial spondyloarthritis, but the benefits of these medications in improving back pain symptoms induced by axial inflammation in psoriatic arthritis.

Post hoc analyses of psoriatic arthritis (PsA) trials have indicated that anti-interleukin (IL)-23 therapy may be beneficial in improving back pain symptoms secondary to axial inflammation; however, treatment with anti-IL-23 agents is not effective for axial spondyloarthritis (axSpA). Authors of a viewpoint published in Annals of the Rheumatic Diseases argue that the efficacy of anti-IL-23 in these conditions was unlikely.

Ustekinumab, guselkumab, and risankizumab are all directed at IL-23 and have been approved for the treatment of patients with psoriasis; ustekinumab and guselkumab have also been approved for PsA. While these monoclonal antibodies were shown to be effective, several randomized controlled trials have shown that they are not effective for patients with axSpA.

The term “physician-reported spondylitis” has been used as a new diagnostic entity following 2 post hoc analyses conducted among patients with PsA with axial symptoms. The diagnosis has been based on the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).

It is still unclear whether axial PsA is a separate entity of PsA or a form of axSpA. Authors of the viewpoint noted they were skeptical of the efficacy of anti-IL-23 therapy in PsA, despite trial findings.

While 2 formal randomized controlled trials (PSUMMIT 1 and PSUMMIT 2) have supported the efficacy of ustekinumab in PsA, data on its efficacy in back pain were based on 2 post hoc analyses of these central studies that assumed that patients with PsA with back pain were similar compared with patients with axSpA.  

The limitations of the post hoc analyses were discussed in detail. First, the studies used BASDAI though the performance of this measure in patients with PsA was limited. Second, while ustekinumab was associated with a decrease in BASDAI, the change suggested only a mild improvement, with the mean change being at a group level and not at an individual level. Third, patients were included in the analyses if there was radiographic evidence of sacroiliitis and not back pain; however, solely relying on imaging may have been a concern especially for PsA due to related degenerative changes. Lastly, evidence for improvement with guselkumab independent of human leucocyte antigen (HLA)-B27 was another limitation that was against the beneficial effect of anti-IL-23 in axial PsA.

Authors Braun and Landewé noted that a bystander effect of general improvement in patients with severe peripheral PsA was responsible for the assumed beneficial effect of anti-IL-23 monoclonal antibodies on the axial skeleton of patients with PsA.

“In conclusion, we think that post-hoc analyses of peripheral PsA trials do not suffice to prove that ustekinumab and guselkumab (or anti-IL-23 treatment in general) are efficacious for ‘real inflammation’ in the axial skeleton of patients with PsA. Far better definitions for axial PsA are needed to be used for inclusion in clinical trials and we strongly support the ongoing Assessment of Spondyloarthritis International Society  ASAS)/Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) initiative in this regard,” the authors concluded.


Braun J, Landewé RB. No efficacy of anti-IL-23 therapy for axial spondyloarthritis in randomised controlled trials but in post-hoc analyses of psoriatic arthritis-related ‘physician-reported spondylitis’? Ann Rheum Dis. Published online October 16, 2021. doi:10.1136/annrheumdis-2021-221422