Management of Difficult-to-Treat Psoriatic Arthritis
In this podcast, Anand Kumthekar, MD, reviews the challenges and approaches to management of patients with difficult-to-treat psoriatic arthritis, including treating non-skin related manifestations of psoriatic disease, optimizing current treatment recommendations, and more.
Additional Resource:
- Kumthekar A, Ashrafi M, Deodhar A. Difficult to treat psoriatic arthritis - how should we manage? Clin Rheumatol. 2023;42:2251-2265. doi:10.1007/s10067-023-06605-9.
TRANSCRIPTION:
Leigh Precopio: Hello everyone, and welcome to another installment of Podcasts360, your go-to resource for medical education and clinical updates. I'm your moderator, Leigh Precopio, with Consultant360, a multidisciplinary medical information network.
A knowledge gap that persists in the management of psoriatic arthritis (PsA) is among patients who have not responded adequately to treatment or who continue to have high disease activity or disease burden and therefore may be considered "difficult-to-treat."
There is a lack of standardization and consensus around the definition of difficult-to-treat psoriatic arthritis and the best course for treatment and management of these patients.
To review what is currently known on the best approaches to management of these patients, Consultant360 is joined by Anand Kumthekar, MD, who is an associate professor in the Department of Medicine, Division of Rheumatology at Montefiore Medical Center and Albert Einstein College of Medicine (New York, NY).
To begin, could you discuss what differentiates an individual with psoriatic arthritis from those with difficult-to-treat psoriatic arthritis?
Anand Kumthekar: That's a good question to start. I think the first thing is we don't really have a clear denition of difficult-to-treat psoriatic arthritis. In our recently published review, we try to give a preliminary definition and we think that a patient with psoriatic arthritis who has been treated according to international guidelines, so either based on guidelines from the American College of Rheumatology, EULAR (European Alliance for Associations for Rheumatology), GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis), which are all these international societies that make treatment guidelines for psoriatic arthritis. If a patient is being treated according to those and has failed three or more biologic disease modifying antirheumatic medications or targeted synthetic disease modifying anti-rheumatic agents, and plus if they fulfill one of the following criteria. So we think if the patient has problematic symptoms based on his or her assessment or the rheumatologist's assessment they can be classified as difficult-to-treat PSA.
The other aspect is if they have a moderate disease activity score based on validated disease activity that is captured in clinic, or they have disease activity in terms of inflammatory arthritis of painful or swollen joints, if they have active skin disease, if they have a lot of axial or lower back symptoms that are problematic, if they are unable to taper their glucocorticoids below seven and a half, or if they have very high inflammatory markers like c reactive protein or ESR, then these patients can be labeled as difficult-to-treat psoriatic arthritis. So, again, they need to fail three or more of newer agents, and then fulfill any of the criteria that I just listed above.
LP: What are some of the challenges associated with managing patients with difficult-to-treat psoriatic arthritis?
AK: So I think the first challenge is, as I mentioned, we don't have a clear definition. So trying to get a clear definition of who these patients are, how would we identify them, I think that's the main challenge.
The second thing in psoriatic arthritis is also now we are trying to use the term psoriatic disease. It's heterogeneous. Patients can not only have skin disease, but can have either peripheral arthritis or painful, swollen joints, axial symptoms. They can have extra articular manifestations like uveitis or inflammatory bowel disease, enthesitis.
The agents that we have today, they do great for the skin. Some of the agents provide more than 90% skin clearance, but we have not made significant progress in terms of treating the arthritis. In the research studies, the patients who achieve either an ACR 70 response is significantly lower compared to patients who have a skin clearance. So I think that's one big challenge in terms of we don't have therapeutics that treat the musculoskeletal manifestation as well as the skin manifestation.
And the other aspect is that patients with psoriatic disease have so many other comorbidities which can really exacerbate their disease activity scores. So trying to capture accurate disease activity scores is still lacking. We do have patient reported outcomes, but I think incorporating some of the objective findings in terms of imaging, either musculoskeletal ultrasound or MRI, that might also be helpful in assessing disease activity of such patients to make appropriate treatment decisions.
LP: There has been a lot of progress in recent years in terms of treatments for psoriatic arthritis. Could you discuss how this may have changed health care practitioners' approach to managing a patient with difficult-to-treat psoriatic arthritis?
AK: Sure. You're absolutely right. There has been significant change in the therapeutic landscape of psoriatic arthritis over the last two decades. So the first trial for psoriatic arthritis was in the 1990s for sulfasalazine. And then we had TNF inhibitors in the early 2000s. And then from 2010 onwards, we have had agents in different classes, like CTLA-4 agonists, IL-17 inhibitors, IL-1223 inhibitors, JAK inhibitors, which have been really beneficial for patients with psoriatic disease.
I think the treatment pattern or how we approach patients with difficult-to-treat psoriatic arthritis or psoriatic arthritis in general has really changed over the last decade or so because of the availability of newer agents. We now have close to 20 years experience of using TNF inhibitors. We think they are relatively safe, although we have to be cautious with the infection risk, but they provide great relief in terms of inammatory burden for patients with psoriatic arthritis. The IL-17 inhibitors or IL-1223 inhibitors also provide a reduction in disease activity for psoriatic disease, but they are great for managing skin symptoms. In someone who has primarily eye disease, we still go for a TNF-inhibitor because that has shown to provide greatest result for uveitis associated with psoriatic arthritis.
So I think, in terms of difficult-to-treat psoriatic disease population, I think incorporating the newer agents, are being incorporated early in the treatment regimen. We know that treating early can prevent radiographic damage and thus, can reduce disability on a long-term basis.
LP: What are some clinical pearls that you utilize in your practice for having a stepwise approach to psoriatic arthritis management?
AK: Psoriatic arthritis, we think around 25 to 30% of patients with psoriasis get psoriatic arthritis. So the first key question is do we have the right diagnosis? The most common arthritis with patients with psoriasis is osteoarthritis, so we have to make sure that we are creating the right diagnosis and the patient truly has psoriatic arthritis and not other forms of arthritis like osteoarthritis, gout, or septic arthritis in rare cases.
Second thing, are we measuring what we are supposed to measure? So are we using the right disease activity measure to capture how active or inactive the disease is. Currently, most of the disease activity measures have patient reported outcomes, though some do include lab values like c reactive protein and sedimentation rate that gives us a sense of if a patient has a mild, moderate, or severe disease activity. So that's the other aspect of it.
Third thing is managing comorbidities. Patients with psoriatic arthritis have a higher incidence of comorbidities like obesity, fibromyalgia, which can really affect their disease activity scores. Fibromyalgia, as you know, is a condition of chronic pain syndrome or central pain sensitization. They usually have a higher level of disease activity and that might not be driven by the inflammatory process of psoriatic arthritis. So changing the modulators might not be the right answer, but doing other interventions like lifestyle changes might be the answer to helping improve their pain levels. Third thing, we should try to optimize the agents that we have. For example, if we are using methotrexate, we should try to optimize the methotrexate. If you're using an IV formulation of a TNF-inhibitor like infliximab and the patient has done well, but not significantly better we can try to maximize this dose or maximize its frequency. So we should really use the available agents to get full potential.
Other aspect is we should also look at patient and system factors, like are patients adhering to their medication and are patients having difficulty getting their medication to insurance? Because that also plays a role in how active their disease is.
And finally, this is not a standard of care practice, but people are looking into whether combination biologic therapy might be the answer for a certain subset of patients who have very difficult-to-treat psoriatic disease, though the verdict is still not out yet.
LP: What are the next steps for research in this area?
AK: The next few exciting things in terms of research in this area are: one, we are trying to see whether treating patients with psoriasis, does it prevent patients from developing psoriatic arthritis? So 70% of patients get psoriasis first, and then they develop psoriatic arthritis. So I think there is a window of opportunity if we treat patients with psoriasis and can potentially prevent psoriatic arthritis.
The second thing is a new mechanism of action in terms of therapeutics, there is a newer agent in which comes in the class of TIK2-inhibitors, which is not approved yet, but the preliminary data is pretty exciting so it is expected that it will be approved in the next year or so.
And the third, I think I briefly mentioned is people are looking into whether a certain subset of patients can be treated with combination biologic therapy if they have very active inflammatory burden from psoriatic disease, But, again, we have to be cautious with the infection risk with combination biologic therapy.
LP: Is there anything else that you would like to add that we did not discuss today?
AK: I would just like to emphasize that psoriatic disease or psoriatic arthritis is a really heterogeneous disease. We have great therapeutics that are available today. Patients with psoriasis who do complain of arthralgia, joint aches and pains, should be sent to rheumatology to make sure that they have psoriatic arthritis or other forms of arthritis because we know that diagnosing patients early and treating them early prevents radiographic damage and long term disability.
LP: Thank you for taking the time to answer my questions.
AK: Thank you so much for having me, and it's great to be here.