Nearly one-third of individuals with psoriasis (PsO) will develop psoriatic arthritis (PsA), and the implications for patient care and long-term management are substantial. According to Philip Mease, MD, Director of Rheumatology Research at the Swedish Medical Center/Providence St. Joseph Health and Clinical Professor at the University of Washington School of Medicine, as treatment options expand and physicians gain access to more data on newer treatments, it may become possible to more effectively meet patients’ needs.
Dr. Mease recently presented long-term data for Tremfya (guselkumab, Janssen) at the American College of Rheumatology (ACR) Convergence. DISCOVER-1 and DISCOVER-2 clinical trials demonstrate Tremfya inhibited radiographic progression versus placebo and provided substantial and durable improvements in joint signs and symptoms, axial symptoms, enthesitis, dactylitis, and pain among adult patients with active PsA. The data also showed a safety profile consistent between adults with active PsA through two years and adults with moderate to severe PsO through five years. Comprehensive efficacy and safety data from the DISCOVER–2 trial of guselkumab were also published in Arthritis & Rheumatology in November.
Dr. Mease addresses some key considerations with regard to psoriatic joint disease and comanagement by dermatologists and rheumatologists.
What are considerations in accessing PsA data?
Dr. Mease: The majority of Tremfya-treated patients who achieved an ACR20, ACR50, or ACR70 response at week 52 maintained the response at week 100, with response rates for ACR50 and ACR70 increasing through the second year of treatment in the DISCOVER trials.
For many of our older treatments, maximum therapeutic response was usually seen by about 16 weeks. With the IL-23s—and the most prominent data we have is with guselkumab—the response curve is continuing to climb at week 12 or 16. In fact, in the DISCOVER 24-week data, the Q8 week dosing of Tremfya did not separate statistically from placebo in radiographic outcomes. Q4 week did, but the Q8 week did not. But we demonstrated that, at the two-year mark, there’s essentially no progression in radiographic structural damage. That is reassuring; being able to demonstrate that 24-week separation versus placebo is tricky in PsA because many patients don’t progress that quickly.
Beyond ACR responses, patients achieve Minimal Disease Activity (MDA) improvement over time, which is a threshold whereby patients are really close to remission. We tend to see that climbing over time, as well.
When I talk to patients at the 16-week mark or the 24-week mark, I can honestly say to them, “There might still be some further improvement. So even if you’re not quite as satisfied as you might be, there’s still room for being in a better state.”
In the study data, we see good results by week 12 or 16, but even better results at week 24, when it’s still placebo controlled. Out to week 52, we see even higher results. Some will point out that without placebo control at week 52, patients’ knowledge that they are on therapy will influence outcome measures. When you apply non-responder imputation or NRI analysis, if the patients move away from the study center, or they drop out for any reason, they’re considered non-responders. Even with that strict analysis, we saw improvements at week 52 and beyond.
I think several things are happening here. First of all, I think that there truly is continued improvement as you inhibit IL-23 over time. I also think that some of the domains that are a little bit tougher to treat—like enthesitis and dactylitis that are not quite as quickly responsive as arthritis or skin disease—continue to respond over time. The fact that we can now demonstrate two years’ worth of not having radiographic progression, further structural damage, is really reassuring.
I think the other factor to keep in mind is that patients are only injecting themselves once every two months. This allows for people not only to have sustained benefit, but it helps put their disease sort of in the back of their minds.
Do you have any thoughts on improving co-management of psoriasis and psoriatic arthritis?
Dr. Mease: One of the things that we are learning is that somewhere around 30 percent, if not a little bit higher, of patients with psoriasis will eventually have psoriatic arthritis. So a significant percentage of the population that dermatologists are seeing are going to either have overt arthritic or enthesial or spine problems or covert problems. Damage can be present but not that symptomatic, or the patient does not realize that they can bring it out with their dermatologist and have it be a meaningful part of the conversation.
I think that it is important for dermatologists to always be aware of this and to have periodic communication about the co-management of their patients.
I am in a private practice. We work really closely with a medical dermatologist in Seattle, with whom we co-manage patients.
The ability to have a dermatologist and a rheumatologist in the same rooms seeing a patient is a rarity and a privilege of being in an academic center.
In practice, we communicate through the EMR or we have a speed dial on our phone where I can speak with any of the dermatologists I tend to work with. I think that the importance of having that cross-communication is really key, and we can teach each other.
The dermatologists are constantly teaching me about how to better assess skin disease or symptoms. They’ve really taught me about how important itch is, for example, which can drive a patient crazy. It’s important to be able to have a drug that controls itch. On the other hand, the dermatologists in my experience don’t really know how important fatigue is for patients. There are cytokine-driven, intracerebral fatigue centers in the brain where fatigue just becomes an overwhelming issue for patients, especially with PsA. In fact, I presented an abstract from some patient focus groups that we did at our clinic and also at the Cleveland Clinic and a group in DC; fatigue was right up there in second place for patients and something that they found that their clinicians were just not addressing with them or talking to them about. That would be another example where dermatologists can learn from us how important some of these types of domains are, as well as looking for weird places for enthesitis to occur in the body and how important that can be for patients. We teach each other.
In my experience, patients are far more likely to be referred from dermatology for management of joint symptoms than for PsO to be identified with joint disease as the inciting concern. However, skin involvement can be inadequately managed by a too-busy rheumatologist not asking about skin disease or assessing skin disease comprehensively, including looking at the scalp and so on.
It’s important to empower patients to be a persistent and to say, “I’ve got a little bit more to talk to you about, including the fact that my skin disease is really active. And I don’t see my dermatologist for another three months. Can we discuss this?”