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Alyssa Johnsen, MD, PhD, spoke with Rheumatology Network about the efficacy of guselkumab for psoriatic arthritis, the challenges of delivering safe and effective treatments in this patient population, and how guselkumab can help improve physical, social, and work activity for these patients.
Rheumatology Network sat down with Alyssa Johnsen, MD, PhD, to discuss findings presented at the recent European Congress of Rheumatology on phase 3b Psoriatic Arthritis (PsA) data that showed guselkumab (TREMFYA®) achieved robust joint symptom improvement and skin clearance in patients with inadequate response to tumor necrosis factor inhibition. Johnsen is the Vice President and Rheumatology Disease Area Leader at Janssen Research & Development. As a part of the EULAR 2021 Virtual Congress, the company presented 34 scientific abstracts, many of which were centered around the efficacy of guselkumab for psoriatic arthritis. We talk about the challenges of delivering safe and effective treatments in this patient population, the clinical significance of these results, and how guselkumab can help improve physical, social, and work activity for these patients.
Rheumatology Network: Why is delivering treatments that are safe and effective so challenging in this patient population?
Alyssa Johnsen, MD, PhD: Well, first of all, psoriatic arthritis is a chronic, arthritic condition that can lead to long term joint damage and even disability. But one of the unique things about psoriatic arthritis when you compare it to other inflammatory arthritities, like rheumatoid arthritis, PsA is unique in that it has multiple domains involved. So, patients also can get skin psoriasis, they can get inflammation of the soft tissues around the joints, they can have both peripheral as well as axial symptoms. So, it really is a multi-domain disease. And we need therapeutic options that treat all of the multiple domains of psoriatic arthritis.
RN: Can you tell me a little bit about the methods your team used in creating the COSMOS study?
AJ: The purpose of the COSMOS was to get additional information even beyond the seminal trials that form the basis of our global regulatory submissions, which have led to multiple global approvals. So, there were 2 seminal trials, the DISCOVER 1 and the DISCOVER 2. And they studied in 1 of the trials, patients who are naive to advance therapies such as biologics, and the other was a mixed population, but most of the patients were naive to biologic therapies and some that had experienced drugs like tumor necrosis factor (TNF) inhibitors. And so, we saw from those studies that guselkumab versus placebo showed efficacy in multiple domains of the disease, including in those TNF experienced patients. What the COSMOS study was designed to do was to study in a dedicated study, that population of patients who had had an inadequate response to TNF inhibitors; so had either inadequate efficacy or a small percentage, less than 20%, had experienced safety issues that caused them to no longer be able to take a TNF inhibitor. So it's really a dedicated study to look at that population, which has historically been more difficult to treat.
RN: And what were the results of that study?
AJ: The results that were that in that population, compared to placebo, guselkumab showed significant a significant difference in arthritis as measured by the American College of Rheumatology (ACR) 20 as well as improved skin clearance measured by Psoriasis Area and Severity Index (PASI) scores, including the PASI 100, which is 100% clearance of skin. So, it showed versus placebo in this more difficult to treat population, guselkumab is a robustly effective therapy.
RN: Can you elaborate on the rapid and durable joint symptom improvement and skin clearance shown in the DISCOVER 1 and 2 studies?
AJ: Sure, I can. So, those are some of the other exciting data that are being presented at EULAR. Now having passed to the primary endpoints for these studies, we're able to look at longer term outcomes for these patients and continue to track these patients as they go past 1 year and 2 years even. And we see that there is a maintenance of response to guselkumab even up to 2 years across the domains tested; so arthritis, tissue, inflammation, skin, as well as imitate inhibition of radiographic progression, which is really fantastic to see. It's incredibly important to physicians and to patients that if they start a therapy and they get an initial good response, they want to see a maintenance of that therapy. So really excited to see that as well. There's data now being presented that as early as 4 weeks you could see decrease in symptoms as measured by the ACR20 so that you can start to see a separation from placebo. So again, you can see an effect relatively rapidly and that effect is maintained up to 2 years.
RN: What is the current safety profile of guselkumab?
AJ: The safety profile has been established, based on the DISCOVER program, as well as in COSMOS, where we see a consistent safety profile. We also have data from psoriasis and there's a relatively consistent safety profile in psoriatic arthritis as well as psoriasis.
RN: How has guselkumab impacted physical, social, and work activity for patients with psoriatic arthritis?
AJ: Psoriatic arthritis is a multi-domain disease, but it also impacts people's social interactions, their ability to work, as well as, you know, diseases like psoriatic arthritis and psoriasis can be associated with symptoms of depression and fatigue. So, in fact, guselkumab has been shown to improve some of these patient reported outcomes that give us an idea of depression and fatigue. We're presenting data on work productivity, and that psoriatic arthritis is associated with decreased work productivity measures, but that guselkumab can improve that and help restore some of that functioning for patients with psoriatic arthritis.
RN: Were there any strengths or limitations of the studies that you'd like to expand upon?
AJ: Well, I mean, I think the strength is that the more data we get on guselkumab and psoriatic arthritis, the better position a physician is really in to make appropriate treatment choices for their patients. And so I’m really excited to have presented in the past the primary endpoint data from DISCOVER 1 and DISCOVER 2. And now we're seeing the long-term data, which can give physicians even more information about the behavior of guselkumab over time, as well as showing in this dedicated TNF inadequate response patient population, significantly different responses, again, showing efficacy. So, I think that's really the strength is that the additional data continues to give us confidence in the efficacy and safety profile of guselkumab.
RN: Does your team plan on doing any further research on this topic?
AJ: Yes. We continue to be very dedicated to bringing new therapies to patients with psoriatic arthritis. And as part of that continue to study guselkumab in this population to better understand the full efficacy and safety profile. We’re dedicated to continue to learn about guselkumab in this patient population.
RN: Is there anything else that you'd like our audience to know before we wrap up?
AJ: I think the one other thing is really what a remarkable innovation inhibition of the interleukin 23 (IL-23) pathway is. Guselkumab is an inhibitor of the IL-23 pathway. One of the things IL-23 does is it's a driver of th17 cells, which are known to be pathogenic in diseases like psoriatic arthritis and psoriasis. So, we're also very committed to the under fully understanding that pathway and all the ways that that inhibiting that pathway may be of benefit to patients with immune mediated diseases. At Janssen, we're very committed to this pathway-focused approach where we address diseases with significant unmet need. And we sort of match them up with driving pathways and also think about all the ways that a particular pathway can benefit patients. So, I think a really important and interesting part of the story as well is that there's still more to come even outside of psoriatic arthritis for guselkumab.
RN: Well, Dr Johnson, thank you so much for speaking with me today. I really appreciate it.
AJ: Thank you very much, I appreciate as well. Thank you so much for your time.