PsA heterogeneity hampers 'meaningful' improvement for therapies
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Clinicians should consider the heterogeneity of psoriatic arthritis when selecting therapeutic options, according to a speaker at the ACR State-of-the-Art Clinical Symposium.
“It is also important to remember that less than one-third of our patients will reach remission on any given therapy,” Alexis Ogdie, MD, director of the Psoriatic Arthritis and Spondyloarthritis Program at the University of Pennsylvania, said in her presentation. “We have a long way to go in terms of therapy outcomes.”
This is evidenced by the fact that even with an expanding therapeutic armamentarium, ACR20 rates are around 50% or 60%, according to Ogdie. “That improvement is not necessarily meaningful to many patients,” she said.
The heterogeneity also makes PsA difficult to study, which compounds the issue of finding the right drug for the right patient. “We are often still not sure how any given therapy will work in any given subset of patients,” Ogdie said.
An additional issue is diagnostic delay. “We are still catching patients too late into their disease. If we can capture them a little bit earlier, we can get better outcomes.”
Moreover, many clinicians still treat PsA like rheumatoid arthritis, according to Ogdie. “There are different types of tissues involved,” she said.
Beyond actual disease parameters, Ogdie noted that patients with PsA can experience comorbidities ranging from diabetes to depression and anxiety. “They experience fatigue, which is multifactorial” and can be marked by sleep disruption and sleep apnea.
Weight loss can be critical to achieving lower disease activity, Ogdie added. But how to achieve that remains uncertain. “We know very little about how diet impacts PsA right now,” she said. “There probably is some impact, but we just do not know.”
PsA is often marked by a circle of depression, inflammation, fatigue, sarcopenia, obesity, comorbidities and pain. With all these factors in mind, Ogdie ran through some of the drugs used to treat PsA.
Regarding methotrexate, Ogdie suggested that the drug has “not that much value” in PsA populations. “It does something, with a 50% ACR20 response rate,” she said. “But the bar is pretty low still.”
As for biologics, Ogdie noted that most rheumatologists are “pretty comfortable” with TNF inhibitors. That said, choosing the right TNF inhibitor and having a grasp on dosing — adalimumab (Humira, Abbvie) has a loading dose of 80 mg, for example — is critical. Higher doses of a TNF may be considered in patients with moderate-to-severe skin disease.
“If the patient has inflammatory bowel disease (IBD) or Crohn’s disease, the picture is complicated,” she added. Infliximab [Remicade, Janssen], adalimumab and certolizumab [Cimzia, UCB] are good choices for patients with uveitis.
Secukinumab (Cosentyx, Novartis) and ixekizumab (Taltz, Eli Lilly & Co.) are the leading interleukin-17 based therapies. Again though, clinicians should consider the specific patient when choosing an IL-17. “There are many different mechanisms of action within the IL-17s,” Ogdie said. “They work well in psoriasis, and there is growing data showing that they work in PsA.”
When choosing between a TNF inhibitor and an IL-17 inhibitor, Ogdie noted that the drug classes are nearly identical in terms of joint parameters, but that head-to-head trials have shown that IL-17s are superior in treating the skin.
The IL-12/23 inhibitor ustekinumab (Stelara, Janssen) and the IL-23 inhibitor guselkumab (Tremfya, Janssen) have shown promise, but there is “still more to learn” about these drug classes, according to Ogdie.
Finally, Ogdie suggested that while JAK inhibitors have shown associations with cardiovascular comorbidities and malignancy, they have shown efficacy in axial disease. “It is just great to know that we have another class that works in these patients,” she said.
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Ogdie A. Update in PsA. Presented at: American College of Rheumatology State-of-the-Art Clinical Symposium. April 9-11, 2021 (virtual meeting).
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