Philip Mease, MD, on Guselkumab for Psoriatic Arthritis
Dr Mease discusses a recent network meta-analysis of studies on guselkumab in treating psoriatic arthritis.
Philip Mease, MD, is the Director of the Rheumatology Research Division at Swedish Medical Center/Providence St. Joseph Health and Clinical Professor of Medicine at the University of Washington.
For more insights from experts like Dr Mease, visit our Excellence Forum.
TRANSCRIPT
Allison Casey: Hello, and welcome to this podcast from the Rheumatology & Arthritis Learning Network. I'm your moderator, Allison Casey. Today, we're joined by Dr. Philip Mease, M.D., Director of the Rheumatology Research Division at Swedish Medical Center, Providence St. Joseph Health, and clinical professor of medicine at University of Washington.
We're going to talk about recent trials of guselkumab for the management of psoriatic arthritis, how it compares to other therapies in safety and efficacy, and the results of a major network meta-analysis. Dr. Mease, thank you so much for joining us today.
Dr Philip Mease: Thank you for having me, Allison.
AC: First question, could you give us a brief overview of the guselkumab trials that were reviewed in this recent network meta-analysis and what that meta-analysis revealed?
Dr Mease: There were three psoriatic arthritis trials of guselkumab that were part of the NMA analysis, DISCOVER-1 and 2 as well as the COSMOS trial. DISCOVER-1 was a trial in patients who had both experience with biologic DMARDs as well as what we call conventional synthetic DMARDs. DISCOVER-2 was in a completely bio-naïve population. COSMOS, which was a more recent study, was in a purely biologic-experienced patient population. It's the spectrum of types of patients with psoriatic arthritis that we see in the clinic, some that have been around the block a few times with various treatments and others that are relatively new to effective biologic or targeted synthetic therapies.
Allison: What were the most important findings in the meta-analysis?
Dr Mease: The network meta-analysis looked at several different outcome measures. One was the ACR 20 response, which is an assessment primarily of musculoskeletal aspects of psoriatic arthritis. Another was the skin response, as measured by the PASI score. A third was looking at the ability of the drug as well as comparator drugs that were part of the network meta-analysis to inhibit structural damage progression, as measured by X-ray. There was also some assessment of safety.
What was found was that from an ACR 20 response point of view, guselkumab compared favorably with other commonly used biologics and targeted synthetic therapies. For example, the subcutaneously injected TNF inhibitors, the IL-17 inhibitors, the JAK inhibitors, and so on. That was reassuring that both the kinetics — meaning the relative speed of onset as well as the overall effectiveness of the drug — is what we want in a drug that is treating the arthritis component of psoriatic arthritis.
In the skin aspect, the PASI score, guselkumab ranked the highest. It ranked higher than any of the other biologic agents or targeted synthetic agents. Not too much of a surprise, because we know that targeting interleukin-23 is highly important in the treatment of the skin aspect of psoriasis.
In terms of the ability to inhibit structural damage progression, there was a slight difference between the q8 week dosing of guselkumab and the q4 week dosing, with the q4 week dosing having better effect on inhibiting structural damage progression.
In terms of safety, the drug did very well. We haven't seen issues related to malignancy, cardiovascular issues, inflammatory bowel disease, and very little in the way of a serious infection rate.
It's a drug that, especially in this time of the pandemic when we are concerned about the safety of our patients, as we should be always, but everybody seems hyper-alert, especially about infection issues, then having a drug that is relatively safe is reassuring to us.
AC: How do these results of the network meta-analysis change the landscape of treatment for psoriatic arthritis? What does guselkumab offer that other therapies don't?
Dr Mease: What this does is it reinforces the confidence that we have in using this agent in treating psoriatic arthritis. We, of course, have the individual trials comparing the drug to placebo, which gives us some degree of reassurance.
In the absence of a head-to-head trial with other medications in the arena of psoriatic arthritis, this is very reassuring to see that the drug is effective and comparable to other agents in treating the arthritis, that it has quite good results in the skin. Especially in the q4 week arm of the treatment, it can have some effect on structural damage progression. There is another trial underway currently being conducted by Janssen to further understand both the q4 week and q8 week effect on structural damage progression. The safety profile is very good. It enters into the pantheon of effective treatments for us. This is important because many of our patients will either not respond to one of the treatments that they're administered, or they may lose effect over time. That's a very common paradigm, unfortunately, in our treatment of these autoimmune diseases. It's very important to have additional classes of drugs and additional medicines within those classes that we can switch to from one drug to another in order to maintain our goal of getting the patients into remission or low disease activity.
AC: You mentioned that some of the trials had patients who were naïve to biologics and some that had experienced other therapies. Was there any difference in the outcomes for those 2 cohorts, or did we see similar effect?
Dr Mease: The best results were seen in those patients that were naïve to biologic agents. There was a bit of blunting of effect in the patients that were previously exposed in the DISCOVER-1 trial and also in the COSMOS trial. We expect that. This is a more recalcitrant patient population that have been around the block several times with previous biologics. The results were more or less what we would have expected for an effective indication.
AC: What are next steps for evaluating therapies for psoriatic arthritis such as guselkumab? Are there any head-to-head trials planned or to be conducted?
Dr Mease: I do know that there are several trials that are getting off of the block in using guselkumab. One example is a trial known as the STAR trial, in which patients who have evidence of what we call axial PsA, meaning they have active inflammation in their spine, are being studied to see the effectiveness of the drug in the spine disease aspect. It's a unique trial, in that only patients who have evidence of active spine disease are being enrolled. There's only one previous study in psoriatic arthritis where that has been done, one called the MAXIMISE trial with secukinumab. That's going to be very helpful for us to understand better the ability of the drug to help patients with the axial aspect of the disease. I already mentioned that there is a trial that's getting kicked off to further look at the ability of the drug to inhibit structural damage progression.
In the future, we're anticipating a very interesting trial, in which guselkumab will paired with a drug known as Simponi, which is golimumab, which is a TNF inhibitor. We do have patients that are very tough to treat, and it's very interesting that we're going to start to see some combination trials of different drugs. I'm not aware if there's going to be a head-to-head trial with guselkumab and any other agent in psoriatic arthritis. These are typically done more in the psoriasis arena. I'm not anticipating, at least in the short run, that we're going to have a head-to-head trial.
AC: Can you talk a little bit about the updated approvals that have already come for guselkumab and what might be coming down the pipe, what it's up for?
Dr Mease: It's already been approved for psoriasis and psoriatic arthritis. Trials are winding up in inflammatory bowel disease, and these trials have shown promising results. We're hopeful that there will be an approval in inflammatory bowel disease. There are likely other trials and other indications that are being thought about, but these are some of the key ones to mention.
AC: Perfect. Thank you. In July, some results were published in Arthritis Research & Therapy from DISCOVER-1 and 2 about guselkumab's effect in reducing fatigue among patients with psoriatic arthritis. Can you talk about how important it is to treat fatigue for these patients?
Dr Mease: I'm glad you asked me that question. This is an area that is very important but often overlooked. We know from patients that second to pain, fatigue is the most troublesome symptom for patients with psoriatic arthritis. This comes out time and again in patient focus groups that we conduct. Fatigue is caused by many different factors, but one of them is the inflammation of the cytokine activity and cellular inflammatory activity that is going on in the body and includes an effect on the central nervous system. The FDA has been aware that patients think of this as a big deal. Fatigue is measured in clinical trials, and we've seen various biologics and targeted synthetic DMARDs benefiting fatigue. We certainly saw that in the DISCOVER-1 and 2 trials with guselkumab. What's interesting is that the FDA has typically resisted allowing beneficial effect on fatigue to enter the label for a drug, because they consider it a somewhat nonspecific symptom.
Given the importance to patients, they're now coming around. Guselkumab was the first drug in PsA where the FDA said, "OK, fine, we agree that fatigue is important, and we'll give you the indication for treating fatigue in psoriatic arthritis." That's something that is good for us to be able to talk to our patients about.
AC: A review from October published in the Oxford Journal of Rheumatology, you mentioned the possibility of IL-23 inhibition benefiting axial psoriatic arthritis and helping to differentiate the immunobiology between axial psoriatic arthritis and axial spondyloarthritis. Can you talk a little bit about those possibilities?
Dr Mease: Yes. There has been a concern historically about whether interleukin-23 inhibition could help the spine aspect of these immunologic diseases. Because of a trial with a different interleukin-23 agent and a Phase 2 trial in ankylosing spondylitis, it did not show differentiation from placebo, and also one with the agent ustekinumab, which did not show benefit compared to placebo in ankylosing spondylitis. We know that there are important differences between the ankylosing spondylitis versus axial psoriatic arthritis. The imaging is different. Some of the clinical features of the disease in the spine are different. We are becoming aware that there are differences in genetics and probably, although this is still to be further explored, in immunobiology.
There was, as I mentioned previously, a very interesting subset of the DISCOVER-1 and 2 studies in which patients with spine pain symptoms that were quite significant, investigators determined presence of axial PsA and imaging evidence of sacroiliac changes consistent with sacroiliitis, an objective marker. These patients showed benefit from guselkumab treatment in spine symptoms. This is giving us some interesting confidence that there may be benefit in axial PsA, even though there may not be in ankylosing spondylitis with this mechanism. Thus, the STAR study that I mentioned earlier, which is looking in a very granular way, including serial MRI scans of the spine, at patients with axial PsA being treated with guselkumab versus placebo.
AC: Definitely, some interesting things coming up. Thank you so much, Dr. Mease, for making the time to speak with us today. This was so great.
Dr Mease: My pleasure. Thanks, Allison.
