Transcript Related Guidelines

Decision Strategies in PsA Management: Role of IL-23 Inhibitors

Eric M. Ruderman, MD · Northwestern University

Disclosures

February 08, 2022

Editor’s Note: The U.S. Food and Drug Administration has approved the anti-interleukin 23 monoclonal antibody risankizumab for treatment of adults with active psoriatic arthritis based on the results of the phase 3 KEEPsAKE 1 and KEEPsAKE 2 trials.[1]

Key Takeaways:

  • Interleukin (IL)-23 is a cytokine of interest in the treatment of psoriatic disease

  • The first dedicated IL-23 inhibitor to be approved was guselkumab; 2 others are in development

  • These agents are attractive because they have less frequent dosing than tumor necrosis factor  inhibitors and IL-17 inhibitors

  • IL-23 inhibitors have been proven effective in skin disease, but their efficacy in treating joint involvement is less clear

This transcript has been edited for clarity.

When it first became clear that the IL-17/IL-23 pathway was important in psoriasis and psoriatic disease, the first agent that targeted that pathway was ustekinumab, which was a combined cytokine inhibitor—an antibody that blocked both interleukin-12 and interleukin-23. 

In recent years, there have been a number of other molecules developed that specifically block interleukin-23, which is really the cytokine that is the target of interest in psoriatic disease rather than interleukin-12. And there’s been some thought that perhaps by not inhibiting interleukin-12, you may actually increase the response to some of these pure IL-23 inhibitors.  

There are now three of them available for use in treatment of psoriasis, and they are all being studied in psoriatic arthritis as well. The first of these, guselkumab, was approved within the last year, and there are ongoing studies with the other two [agents]. Like the IL-12/23 inhibitor ustekinumab, these agents are attractive because they have a more infrequent dosing schedule than either TNF inhibitors or interleukin-17 inhibitors. 

They’re given either every 2 or every 3 months as a subcutaneous injection, which is much easier than a weekly injection. They’re definitely effective in psoriatic arthritis; the phase 3 studies with guselkumab showed clear-cut efficacy in a placebo-controlled trial, and the drug was approved on the basis of those studies. 

It’s not clear, though, whether it is as effective, more effective, or less effective than other biologics, [such as] TNF inhibitors or IL-17 inhibitors, at least for joint disease. For skin disease, the IL-23 inhibitors seem to be the most effective antibodies, the most effective biologics, that we have, to date, for psoriatic skin disease. 

For joint disease, it’s not clear yet where these agents fit in because we don’t have a lot of clinical experience, since the first of these has only just been approved. We’ll have to see as time goes on. The second agent, risankizumab, recently released results from its phase 3 trials, and I anticipate that [those data] will be going to the FDA at some point in the next year for evaluation for psoriatic arthritis, so we’ll see if that’s another alternative. 

These drugs are particularly appealing in patients with really severe skin disease because of their effectiveness there. Patients like them because they’re given infrequently, but whether they’re going to be quite as good for joint disease, I think we’re just going to have to monitor clinical response, as we continue to treat patients. 

The last thing I would note about the IL-23 inhibitors, similar to concern that’s been raised about the IL-12/23 combined inhibitor, is the effectiveness in axial disease and whether these agents are going to work in the psoriatic patients who have axial involvement and inflammatory spine disease. 

Risankizumab was studied in the clinical trial in ankylosing spondylitis, and it was not effective in that trial. In the psoriatic arthritis trials with guselkumab, they looked at BASDAI scores, which theoretically measure a response of the axial disease in those patients who described prior actual symptoms, and there was a suggestion that they improved. 

I think it’s unclear whether the BASDAI is really a pure axial score or whether that represents overall response and joint disease. So, again, I think there will be some need for clinical experience over time to tell us whether the IL-23 inhibitors are as effective as a TNF inhibitor or IL-17 inhibitor for patients with psoriatic arthritis who have significant axial disease. 

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