‘PsA is all about the domains’: Tailoring therapies to disease involvement pivotal for PsA
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DESTIN, Fla. — Understanding which psoriatic arthritis disease domains are most important to the patient may help guide therapeutic decision-making, according to a presenter at the 2023 Congress of Clinical Rheumatology-East.
“PsA is all about the domains,” Arthur Kavanaugh, MD, a rheumatologist and professor of medicine at the University of California, San Diego, told attendees. “Different domains respond to different types of therapies.”
Regarding those domains, Kavanaugh suggested that enthesitis occurs in approximately 30% of PsA patients, while dactylitis occurs in one-quarter, spondylitis ranges from 7% to 32%, nail involvement occurs in 60% and uveitis and IBD are reported in about 3% each.
Moreover, about 25% of patients with psoriasis will go on to develop PsA, according to Kavanaugh. However, this data point is exemplary of the challenges in this disease. “But we don’t know who [will develop PsA],” he said.
While it is thought that the microbiome may influence this progression, this has not yet been proven. In the absence of this certainty, Kavanaugh offered an important tip for clinicians. “You have to go into the room and talk to the patient,” he said.
Talking to the patient is the starting point for making therapeutic decisions. In most cases, methotrexate remains the first-line option for many PsA patients. However, questions remain about what to do when this drug begins to lose efficacy. The data are inconclusive.
“People who added a TNF inhibitor to methotrexate did better,” he said. “But some patients did better adding more methotrexate.”
Regarding biologic therapies, rheumatologists are learning “bedside to bench,” according to Kavanaugh.
“TNF inhibitors are still the mainstay,” Kavanaugh said. He suggested that the most important quality of this drug class is the capacity to minimize disease progression.
“If you do not have swollen joints, and you have low CRP, you are not going to get X-ray progression,” he said.
The other class that has gained widespread use in recent years is janus kinase inhibitors.
“JAK inhibitors seem to be checking a lot of boxes,” he said, noting that they can work “across multiple domains of disease,” including skin, joints, dactylitis and axial manifestations.
But as more JAK inhibitors are approved, new challenges arise. “We do not know how to pick them just yet,” Kavanaugh said.
Regarding other agents, interleukin-6 and IL-1 inhibitors have shown less efficacy in skin or axial disease, while IL-17 inhibitors have recently shown a small effect in peripheral disease.
As clinicians continue to learn about biologics, the advent of biosimilars will offer new opportunities but raise new questions, according to Kavanaugh. “We are overcoming our innate resistance to biosimilars,” he said. “Inherently, we hate to switch patients. But, scientifically, it is really hard to push against it. They are coming, and they will have a big impact on our treatment algorithms.”
Moving away from the specifics of treatment decision-making, Kavanaugh stressed that choosing a medication to target a specific domain is just one part of PsA management.
“Women start with a higher disease activity and do not respond as well as men, no matter what treatment we give them,” he said. “We do not know the basis for this.”
Another question pertains to tapering patients or discontinuing treatment altogether when a patient is doing well. “Patients who stay on therapy tend to do better,” Kavanaugh said. However, even patients who stay on therapy “sort of come in and out” in terms of response.
That said, patients who discontinue treatment altogether more frequently fail to continue to meet minimal disease activity benchmarks.
Kavanaugh challenged researchers to conduct more nuanced studies about tapering or reduced dosing.
Other potential areas of research should investigate alternating agents or combination therapies, according to Kavanaugh. “We still have not figured out how to sequence agents,” he said. “Maybe combination therapy is an idea we can revisit, but we just have to think about what combination of agents.”
As researchers continue to explore these questions, Kavanaugh offered some over-arching advice for attendees. “How do we pick therapies?” he said. “We should pick them based on what domains are important to the patient.”
With this in mind, he offered one other comment. “The earlier we treat, the better we do.”
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Kavanaugh A. Psoriatic arthritis: Newest approaches to therapy? Presented at: Congress of Clinical Rheumatology-East annual symposium; May 4-7, 2023.
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