Dual therapy can have ‘synergistic effect’ in difficult-to-treat inflammatory diseases
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SAN DIEGO — Certain dual therapy strategies, including interleukin-17 plus IL-23 inhibition, or Janus kinase inhibitors alongside TNF inhibitors, can be effective for difficult-to-treat inflammatory diseases, according to a speaker here.
“We all have many patients in our practice — rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, lupus, et cetera — where you’ve tried many things, and they’re breaking through,” Philip J. Mease, MD, director of rheumatology research at Swedish Medical Center/Providence-St. Joseph Health, in Seattle, told attendees at the 2024 Congress of Clinical Rheumatology West. “What do we do?”
Mease stated that his clinic has more than 100 patients with psoriatic arthritis and spondyloarthritis on dual therapies, such as IL-17 plus IL-23 inhibition, and JAK inhibition plus TNF inhibition. However, such combinations can carry risks, he added.
“When we do this in the clinic we’re very, very careful to explain that it’s uncharted territory, it’s off-label and to be extremely vigilant for infection issues,” Mease said.
According to Mease, these patients have already tried multiple treatments, and some are bridging between an old drug and a newer one while others are receiving ongoing dual therapy.
“The most successful we’ve been in getting insurance to cover this is if we as rheumatologists prescribe one medication and gastroenterologists or dermatologists prescribe the other,” he said. “So gastroenterologists obviously may prescribe vedolizumab, which is a gut-specific acting inhibitory drug for colitis, while we give a TNF inhibitor, for example, or an IL-23 inhibitor for musculoskeletal manifestations.”
Clinical trials are beginning to explore dual therapies after previous efforts resulted in a significant increase in infections, but little efficacy benefit, according to Mease.
As an example, he highlighted the VEGA trial, which was published in 2023 and tested the combination of golimumab (Simponi/Simponi Aria, Janssen) and guselkumab (Tremfya, Janssen) for the treatment of ulcerative colitis. The trial found the combination demonstrated a “multiplicative effect,” driving down pro-inflammatory genes and upregulating anti-inflammatory genes to a greater degree than would be expected from simply adding the drugs’ effects together, with no safety cost, Mease said.
“This is, to me, a sign that we should be doing more and more like what the oncologists do, and that is understanding what’s driving their gene expression and then thinking about optimal combinations of drugs to put together to get this kind of synergistic effect,” he added. “Especially early on, when the disease is still at a place where we don’t have much damage, and we can potentially change the overall course of the disease.”
Mease also discussed his involvement in the upcoming Group for Research and Assessment of Psoriasis and Psoriatic Arthritis project to gather experiences with dual therapies from around the globe.
The use of dual therapy strategies can also be aided by criteria defining patients with disease that is difficult to treat or manage, he said.
Such criteria are “incredibly important for pharmaceutical teams who are designing trials, to have the courage to put two dual biologic therapies together, know that you may get more side effect issues that you then have to report, but know as well that this is a significant unmet need,” he added.
“And we need the data in order to be able to turn to the payers and our regulatory people to say, OK, this is an important new area for us to be moving into,” Mease said. “Or not, if it turns out that a particular combination doesn’t have that much benefit or has an especially harsh safety outcome.”
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Mease PJ. Axial Spondyloarthritis: Hot Topics and Treatment Update. Presented at The Congress of Clinical Rheumatology West; Sept. 26-29, 2024. (hybrid meeting).
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