Despite abundance of biologics for PsA, disease domains 'dictate treatment'
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Although a range of biologic options are available to clinicians treating psoriatic arthritis, it crucial to know which disease domains are involved as this will “dictate treatment,” according to a presenter at the Biologic Therapies Summit.
Arthur Kavanaugh, MD, professor of medicine in the department of rheumatology at the University of California, San Diego, zeroed in on biologic drug classes, including interleukin-12/23 inhibitors, IL-17 inhibitors, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)-based therapies, janus kinase (JAK) inhibitors and phosphodiesterase type 4 (PDE4) inhibitors. “We are blessed with a surfeit of available therapies,” he said.
Some of these classes are more beneficial for musculoskeletal complications of PsA, while others show improvement in skin or nails. “You have to know what domains are involved,” Kavanaugh said. “That will dictate treatment.”
But Kavanaugh also encouraged every rheumatologist to be a “clinician and therapeutic immunologist” by weighing not only disease domains, but intangible factors such as clinical experience and patient preferences when selecting therapies.
He reviewed the “plethora” of biologics available, and how they may be used to optimal efficacy in PsA.
The primary benefit for TNF inhibitors can be in patients with enthesitis and dactylitis, according to Kavanaugh. However, “very dramatic effects” have also been seen in preventing radiographic damage. “All the domains get better which, of course, is very useful,” he said.
Regarding IL-12/23 inhibitors like ustekinumab (Stelara, Janssen), the effect on skin PsA is undeniable, according to Kavanaugh. “This was a game changer,” he said of early data showing this effect. “It let us know that there can be something better than TNF inhibitors.”
Kavanaugh added that ustekinumab can be effective in peripheral arthritis and enthesitis. However, another IL-12/23 inhibitor, risankizumab (Skyrizi, Abbvie) may not be effective for axial disease in PsA.
IL-17 is a “complex family of cytokines,” according to Kavanaugh. He added that IL-17-targeted therapies such as secukinumab (Cosentyx, Novartis) and ixekizumab (Taltz, Eli Lilly & Co.) have different mechanisms of action. The conventional thinking, though, is that IL-17 inhibition is generally superior to TNF inhibition for skin and nail effects of PsA.
“Secukinumab was almost close to being superior to TNF inhibitors for articular manifestations,” Kavanaugh said.
IL-17 inhibitors come with a caveat pertaining to inflammatory bowel disease (IBD). “There is a question about whether they may allow some patients to worsen with IBD,” Kavanaugh said.
The PDE4 inhibitor apremilast (Otezla, Amgen) is a “fascinating drug” that may show greatest benefit in oligoarticular PsA, according to Kavanaugh. “It has an incredibly good safety profile in general,” he added.
Regarding IL-23 inhibitors that do not block IL-12, Kavanaugh suggested that guselkumab (Tremfya, Janssen) can be effective for peripheral arthritis and skin PsA with a very large effect size similar to or better than some other agents. “It is an important consideration as we think across the different domains of involvement and choose a therapy,” he said.
Clinicians and researchers are still considering the optimal target for JAK inhibitors, according to Kavanaugh. That said, tofacitinib (Xeljanz, Pfizer) may have utility in peripheral arthritis. While tofacitinib may not have as robust a response in the skin as some other options, it can work in enthesitis and dactylitis.
Kavanaugh closed with some thoughts on the movement toward precision medicine in rheumatology. “More work needs to be done,” he said.
While PsA treatment would clearly benefit from reliable biomarkers to target therapies to individual patients, Kavanaugh stressed that the complexity of the disease might make that a big challenge. “We want one biomarker that is going to be a home run,” he said. “That is not going to happen in PsA. It is too heterogeneous of a disease. It’s a complex equation.”
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Kavanaugh A. Evolving treatment strategies in PsA: How do we choose? Presented at: Biologic Therapies Summit IX; May 21-23, 2021 (virtual meeting).
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