Better use of cytokine signalizing could ‘revolutionize’ rheumatology treatment
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Correctly identifying cytokine pathways that are dysregulated in any given rheumatology patient could lead to better use of current biologic therapies, said a presenter at the 2022 Association of Women in Rheumatology annual conference.
“We need to talk about cytokine signaling,” Iain B. McInnes, MD, of the University of Glasgow, told attendees at the hybrid meeting.
McInnes noted that despite advances in therapeutic development resulting in biologic and biosimilar medications, rheumatologists still face challenges in the clinic.
“We can’t repair our patients very well,” he said. “The way we think about the future is going to have to evolve.”
Biologic medications can be likened to “molecular scalpels,” according to McInnes. Early biologics could target a single cytokine pathway, such as interleukin-6, IL-17 or TNF.
“We have learned that cytokine-targeted therapies make people feel better,” McInnes said.
However, he believes the rheumatology community has “made a lot of mistakes” when it came to application of these “exquisite molecular scalpels.”
For example, IL-6 inhibition was highly effective in rheumatoid arthritis and giant cell arteritis, but largely ineffective in psoriasis, psoriatic arthritis and the spondyloarthropathies.
“We don’t celebrate our failures, and I think that is a mistake,” McInnes said. “We should learn from our failures to a far greater degree than we do from our success.”
That said, treatments have continued to evolve.
“Kinase is the first foray into poly-cytokine inhibition,” McInnes said.
Although a variety of Janus kinase inhibitors can target multiple pathways, diagnostic technology and biomarkers are not yet able to decipher which pathways are dysregulated in any given patient.
“JAK use is not optimized,” McInnes said.
Because clinicians are unable to identify the exact cytokine pathways that are implicated, current treatment paradigms are organ-based, according to McInnes. He noted that rheumatologists determine whether the joints, skin, gut, kidney or other organ system is impacted most heavily and assign a treatment accordingly. He argued that the future of rheumatology treatment should be based on the molecular pathway that is dysregulated.
McInnes looked to a “cytokine-centric future” of rheumatology treatment.
“We need to think about these cytokine models across different diseases,” he said.
However, McInnes does not recommend abandoning organ-based treatment strategies altogether. He offered the example of an airplane traveling thousands of miles and then ultimately arriving at its destination.
“Organs will get us into a holding pattern above Heathrow airport,” he said. “Then use cytokines to land the plane. We are not flying blind here.”
If a clinician is able to discern the molecular pathways before treatment begins, the targeted therapies currently in the armamentarium would be that much more effective, according to McInnes.
“A molecular signature will lead us to immune homeostasis, tolerance and repair,” he said. “It could revolutionize the strategic management of our patients.”
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McInnes I. Cytokine signatures and signaling, a new approach to defining IMIDs. Presented at: AWIR Annual Conference; August 18-21, 2022; Hilton Head Island, South Carolina (hybrid meeting).
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