'Sweet spot' in PsA treatment remains elusive despite therapeutic advances
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A broader array of therapies is allowing clinicians to target specific disease domains in psoriatic arthritis, but the treat-to-target “sweet spot” remains unclear, noted a presenter at the 2021 Congress of Clinical Rheumatology-East.
“Five or 10 years ago, when we were treating psoriatic arthritis, we would try anything,” Iain B. McInnes, MD, PhD, of the University of Glasgow College of Medical Veterinary and Life Sciences, in the United Kingdom, told attendees. “We needed new modes of action.”
He described earlier PsA treatment as a “hand-me-down” drug development program due to many of the drugs coming from rheumatoid arthritis. “Now we have the option of choice,” he said.
That choice is largely centered on whether the patient has more skin or nail disease, more enthesitis, axial skeleton involvement or if their disease is swollen joint dominant. McInnes noted that advances in laboratory analysis, along with a raft of recent clinical trial data, have given clinicians a better understanding of how to treat each of those targets. “We now have clear evidence that different tissues will behave differently on different interventions,” he said.
Looking at specific therapies, McInnes started with methotrexate. He suggested that this drug may not be the anchor drug that it is in RA. “Use of methotrexate is based on astonishingly few clinical data,” he said, but acknowledged that he will start a patient on this drug. “If they are only getting a partial response, we think pretty quickly of escalating therapy.”
Regarding TNF inhibitors, McInnes said they are “the tried and the trusted” therapies for PsA. An important clinical question about this class of drugs, however, was whether these drugs led to erosive progression. “TNF blockade is actually anti-erosive in PsA,” he said.
Other recent clinical trial data have shown clear evidence that the interleukin-17/IL-23 axis is “pathogenically relevant” in PsA. Accordingly, these classes of drugs are being used more widely to increasing efficacy.
The IL-23 inhibitor guselkumab (Tremfya, Janssen) can yield a “very nice, robust response” in dactylitis and enthesitis, according to McInnes. He noted that clearance of dactylitis can be seen in some three-quarters of patients, while about 60% will resolve enthesitis.
Along the IL-17 pathway, the IL-17a inhibitor secukinumab (Cosentyx, Novartis) has also shown strong efficacy in dactylitis and enthesitis in addition to anti-erosive properties, according to McInnes. He added that ixekizumab (Taltz, Eli Lilly & Co.) may have even “higher potency” in these responses.
Beyond dactylitis and enthesitis, McInnes noted that IL-17 inhibition can also yield positive response in the axial skeleton.
Turning to p19 inhibitors, McInnes suggested that this class of drugs can lead to similarly robust response in the skin. “More than even a TNF inhibitor,” he said. However, further investigation is needed.
While McInnes stressed that there can be pitfalls in comparing clinical trial results, 30,000-foot comparisons are starting to reveal trends in PsA treatments. “For someone with skin-dominant disease and some swollen joints, IL-17 is probably a better choice than a TNF inhibitor,” he said. “However, IL-17 is not good for gastrointestinal tract involvement. It may, in fact, exacerbate inflammation.”
TNF inhibition, on the other hand, is likely to have a greater impact on patients who are synovium dominant.
“P19 is better in skin and joints, but we don’t know yet about the axial skeleton,” McInnes added.
Moving along the pipeline, the janus kinase (JAK) class of drugs may have utility, but further investigation is necessary. “If janus kinase works, it is because there is some kind of intracellular crosstalk going on,” he said.
JAK inhibition trends toward stronger outcomes in the skeleton, while the impact on skin and joints remains uncertain, according to McInnes.
Despite these advances, McInnes believes there is still considerable work to be done. “The sweet spot in psoriatic arthritis is absolutely unclear,” he said. “It is completely different from treat-to-target in rheumatoid arthritis.”
But McInnes sees some positives in the increasing array of treatments for the variable patients he sees each day. “It allows me to treat the person in front of me,” he said.
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McInnes IB. Psoriatic Arthritis – What’s New and Should We Care? Presented at: Congress of Clinical Rheumatology-East annual symposium; August 12-15, 2021 (hybrid meeting).
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