Dr Orbai, from Johns Hopkins University, recaps a presentation on the findings of a trial of guselkumab for the treatment of psoriatic arthritis at ACR Convergence 2021.
 

Ana-Maria Orbai, MD, is an assistant professor of medicine and director of the Psoriatic Arthritis Program at the Johns Hopkins School of Medicine in Baltimore, Maryland.

TRANSCRIPT:

Welcome to another podcast from the Rheumatology & Arthritis Learning Network. I'm your moderator, Rebecca Mashaw. Today, Dr. Ana-Maria Orbai has come back to speak with us about one of her poster presentations from the recent American College of Rheumatology Convergence meeting.

She previously spoke with us about the validation of the PROMIS-29 profile for patients with active psoriatic arthritis. Today, she is going to continue that theme and talk to us about her research into how this tool measured general health outcomes among patients with psoriatic arthritis who are being treated with guselkumab during the phase 3 DISCOVER-1 trial.

It's nice to have you with us again, Dr. Orbai.

Dr. Ana-Maria Orbai:  Thank you. My pleasure to return and tell you more about our research.

Rheumatology & Arthritis Learning Network:  Wonderful. Let's talk about this clinical trial. What were the primary endpoints?

Dr. Orbai:  The primary endpoints of the DISCOVER-1 trial were the ACR20 indices, which are traditionally measured as primary outcomes in any clinical trial of treatment for psoriatic arthritis. In addition to these traditional outcomes, we also focused on more specific outcomes for psoriatic arthritis like minimal disease activity, enthesitis and dactylitis .

Then, of course, there was the objective of this research on health-related quality of life measured with the PROMIS-29 profile.

RALN:  Your abstract title refers to clinically meaningful improvements in health outcomes. Can you tell us how you define clinically meaningful? How did you measure those outcomes?

Dr. Orbai:  Rebecca, that's a great question. With any intervention, we want to make sure that we don't just demonstrate statistically significant changes. We want to make sure that the changes are also meaningful for patients. So we proposed to look at this.

PROMIS-29 does not have clinically meaningful thresholds defined in psoriatic arthritis. However, based on evidence from other diseases, a change of .5, even .3, standard deviation in the direction of improvement on these tools was demonstrated in a general population and disease populations to be significant for patients.

Our question was, does treatment with guselkumab in this clinical trial lead to improvements that are at the magnitude of a .5 or a .3 standard deviation for patients with psoriatic arthritis?

RALN:  This is an anti-interleukin-23 p19 subunit monoclonal antibody. How might this particular mechanism of action be different from existing therapies, and what would give it an advantage in treating active psoriatic arthritis?

Dr. Orbai:  We know that key players in psoriatic arthritis that have emerged are interleukin-23, interleukin-17, and the TNF. For a long time, we had TNF inhibitors. We've been working with these drugs 20-plus years. Then in the past few years, interleukin-23 and interleukin-17 have emerged as the axis of psoriatic disease.

Interleukin-17-producing salts are dependent on interleukin-23. This is a new pathway that potentially acts earlier on in the inflammatory cascade of psoriatic disease. It has great efficacy. It's currently an FDA-approved therapy for both psoriasis and psoriatic arthritis, based on phase 3 data from 3 clinical trials.

The question was, does it improve psoriatic arthritis comprehensively in all its dimensions? And I think this has been demonstrated. We are now also trying to triangulate that with newer tools like the PROMIS-29 profile.

RALN:  You've effectively answered my next question, which was what did you find out about the efficacy for this medication among patients with active PsA?

Dr. Orbai:  DISCOVER-1 clinical trial included 381 adults with active psoriatic arthritis and inadequate response to standard nonbiologic therapies, of which 31% were TNF inhibitor-experienced. Patients had active psoriatic arthritis with an average tender joint count of 20 and swollen joint count of 10, and a pain score of 6 out of 10.

The first observation in the study was that, as expected, mean baseline PROMIS-29 scores were worse than the general population. In the DISCOVER-1 clinical trial, patients with active psoriatic arthritis had mean PROMIS-29 domain scores that were worse than the general population.

For example, for physical function, the average score was 40, a full standard deviation worse than the general population mean. For pain interference, this difference was 2 standard deviations worse, close to a score of 70.

After treatment with guselkumab at week 24, there were clinically significant improvements in physical function. The average improvement was half a standard deviation, as we had planned to demonstrate, as well as improvements in pain interference, social participation, and sleep.

These improvements were durable through week 52, showing that continued treatment was beneficial for these patients.

RALN:  If I understand what you're telling us then, guselkumab turned out to be very efficacious in relieving pain and fatigue, and improving physical function among patients with psoriatic arthritis, and that it remained a durable improvement over a year. Is that correct?

Dr. Orbai:  That is correct.

Rebecca:  What about safety and adverse events? What did you find out about those aspects?

Dr. Orbai:  With any biological treatment, we look out for infections. These have been previously reported with guselkumab, and there were no additional signals. In fact, guselkumab seems to be one of the safer treatment options in our therapeutic panel for psoriatic arthritis.

RALN:  This agent is one of those that is effective even in patients who have failed previous biologic therapies?

Dr. Orbai:  That is correct; 30% of the participants in these trials have already failed TNF inhibitors.

RALN:  So this is a very promising addition to the armamentarium for clinicians who are treating patients with psoriatic arthritis.

Dr. Orbai:  Absolutely.

RALN:  Wonderful. That's great news. Thank you again for joining us, and we'll look forward to hearing about continuing studies.

Dr. Orbai:  Thank you. My pleasure.