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Division of Rheumatology
Department of Medicine
University of Toronto
University Health Network
Vinod Chandran, MBBS, MD, DM, PhD, has disclosed that he has received funds for research support from AbbVie and Amgen and consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Lilly, Novartis, Pfizer, and UCB.
In psoriatic arthritis (PsA), axial manifestations can be common: At least 25% of patients with PsA have axial involvement and another 15% develop it after 10 years of follow-up. And although not all patients with PsA have axial involvement, it is an important domain and is often associated with more severe disease.
Treating Axial Manifestations of PsA
Until recently, clinical trials in PsA did not evaluate the efficacy of advanced targeted therapies in improving axial manifestations—they focused solely on peripheral arthritis, dactylitis, enthesitis, and skin psoriasis.
Lacking these specific data—and assuming a common underlying pathophysiology—treatment recommendations for the axial manifestations of PsA were similar to those for axial spondyloarthritis/ankylosing spondylitis.
But this may be changing, as recent developments have questioned these assumptions and recommendations.
In PsA, the efficacy of inhibition of IL-17A, IL-12/23, and IL-23 by secukinumab, ustekinumab, and guselkumab, respectively, is well established. But what about their effects on axial manifestations of PsA?
In patients with PsA and axial manifestations, a recent randomized, controlled phase IIIb trial demonstrated the efficacy of secukinumab (an IL-17A inhibitor) in improving axial disease compared with placebo. Specifically, secukinumab significantly improved Berlin MRI scores vs placebo, thus providing objective evidence of reduced inflammation in the spine and sacroiliac joints in PsA.
This was the first time that the efficacy of a biologic disease-modifying antirheumatic drug in axial manifestations of PsA was demonstrated.
However, there were some significant drawbacks: lack of an accepted definition of axial PsA and the inability to dissociate improvement in axial disease from overall improvement in psoriatic skin and joint disease using patient-reported outcomes.
And what about IL-23 inhibition? Since 3 randomized, controlled trials failed to demonstrate efficacy of the IL-12/23 inhibitor ustekinumab in axial spondyloarthritis, and since a clinical trial with the IL-23 inhibitor risankizumab also failed to demonstrate efficacy in ankylosing spondylitis, one might conclude that IL-23 does not drive disease symptoms in axial spondyloarthritis and therefore would not be useful for axial manifestations of PsA.
However, a post hoc analysis demonstrated the efficacy of guselkumab in improving axial symptoms in patients with active PsA who have imaging-confirmed sacroiliitis.
Thus, even though IL-23 it is not likely to be a driver of axial spondyloarthritis, it may be an important driver of axial symptoms in PsA.
To facilitate further clinical and translational studies, ASAS and GRAPPA are currently working together to develop a new definition of axial PsA. Once axial PsA is formally defined, differences between axial spondyloarthritis and axial PsA can be formally evaluated. Furthermore, response criteria for axial PsA clinical trials will be developed and validated. Only then can appropriately designed clinical trials with IL-23 and other cytokine and small molecule inhibitors be conducted and this important unmet need answered.