Transcript Related Guidelines

Axial Psoriatic Arthritis

Philip J. Mease, MD, MACR · University of Washington

Disclosures

August 12, 2021

Key Takeaways:

  • Treatment recommendations for axial disease and psoriatic arthritis have been based on data from clinical trials for axial spondyloarthritis or ankylosing spondylitis

  • However, axial spondyloarthritis and axial disease in psoriatic arthritis (axPsA) differ in terms of the development of axial manifestations, genetics, clinical manifestations, and radiography and other imaging 

  • Recent clinical trial data suggest that patients with axPsA without MRI positivity may have very good responses to secukinumab

  • Another clinical trial, data from which should be considered preliminary, showed improvement of guselkumab-treated patients with axPsA and raises the question of whether axPsA is immunobiologically different enough from spondyloarthritis such that an IL-23 inhibitor might be effective

This transcript has been edited for clarity.

I'm going to be discussing the general subject of axial PsA, and how it may differ from axial SpA, and optimal treatment approaches. Historically, treatment recommendations have addressed the issue of axial disease and psoriatic arthritis, which occurs in approximately 40% to 50% of patients with psoriatic arthritis.[1] However, the treatment recommendations have been based on the data from axial spondyloarthritis or ankylosing spondylitis clinical trials, and we've used that as a surrogate for evidence for efficacy in axial PsA. 

We're now beginning to understand though that there may be important differences between axial spondyloarthritis, or AS, and axial disease in psoriatic arthritis, or axPsA. For one thing, the patients often develop their axial manifestations of PsA slightly later. The disease may begin peripherally and then involve the spine. So we know that in early-stage disease, 5% to 28% of patients have immunologic inflammation, but then as they become more long-standing, up to 70% may do so.[2] 

We also know that there are important genetic differences in ankylosing spondylitis. Certainly, HLA-B27 may be present in up to 85%, 90% of patients, as well as other HLA-B genes. In axial PsA, we see HLA-B27 positivity, but only in 25% to 30%, whereas HLA-B8, HLA-B38 or 39, or HLA-Cw are important genes in axial PsA.[3,4] 

We also know that, radiographically and otherwise imaging-wise, that there may be important differences. For example, in axial PsA, we may see asymmetric sacroiliitis, especially associated with the HLA-B8 gene phenotype, whereas in ankylosing spondylitis or axial spondyloarthritis it's more often symmetric. 

Furthermore, in the spine, syndesmophytes may be patchy in their formation in axial PsA as opposed to symmetric and from one vertebral body to another contiguously in ankylosing spondylitis. Also, the morphology of the syndesmophytes is different in PsA, looking chunkier. 

Another important difference has to do with clinical manifestations. So, for example, patients with axial PsA may be asymptomatic. They may not endorse inflammatory back pain symptomatology. They [patients with axPsA] tend to have quite a bit of peripheral arthritis, enthesitis, be more female, or equally female as well as male—all different from axial spondyloarthritis. Does this matter? Well, let's ask the question of some of the more recent clinical trials. 

We know that in the study MAXIMISE, in which secukinumab was studied against placebo in a dedicated axial PsA study, the patients responded very well. One of the findings was that, whereas 60% of the patients had abnormal MRI scans of the spine and sacroiliac joint, 40% did not.[5] They did not light up in the MRI. But they had very good responses nonetheless to secukinumab. So this is an important group of patients that may not have MRI positivity. 

In recent times, there have been some studies of interleukin-23-inhibiting medications in [the] treatment of ankylosing spondylitis. These studies have not shown improvement in the patients treated with IL-23 inhibitors compared to placebo. This was the case with the study with risankizumab, a small AS study, as well as ustekinumab.[6,7]

So for a while, we were thinking, OK, IL-23 for some reason immunobiologically may not work in treating ankylosing spondylitis, even though IL-17, downstream from IL-23, does. However, the most recent trial looking at spine response with an IL-23 inhibitor raised questions about this assumption. 

In the psoriatic arthritis phase III program known as the DISCOVER trials with guselkumab, a p19 IL-23 inhibitor, a subgroup of patients were identified whom the investigators thought had axial PsA, and they also had abnormal imaging of the sacroiliac joints consistent with sacroiliitis.[8] 

What turned out was, when various measures of spine disease were applied—including, for example, the overall BASDAI score, the spinal pain question of the BASDAI, as well as the slightly more objective ASDAS measures—we saw improvement in the guselkumab-treated patients as compared to placebo, even in those patients with ASDAS major improvement in active disease. So this raises the question, is axial PsA immunobiologically different enough from axial spondyloarthritis such that an IL-23 inhibitor might work? 

I consider the DISCOVER data to be preliminary. And what will proceed is a dedicated study in axial PsA being conducted with this medication, including MRI scanning and abnormality documentation at baseline, and then tracking MRI scanning throughout the course of the study. 

Of course, we still need a better definition of axial PsA. And the GRAPPA group, working together with ASAS, is coming together to do a classification criteria development study in 400 patients so that we can actually study this more carefully.  [12]

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