‘We should be thinking cure’ for giant cell, Takayasu arteritis as trial data grow
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SAN DIEGO — A growing body of clinical trial data are increasingly guiding the treatment landscape for giant cell and Takayasu arteritis, according to a presenter at the 2023 Congress of Clinical Rheumatology West.
“Despite the challenges in studying GCA, treatment is increasingly guided by data from clinical trials,” Peter A. Merkel, MD, MPH, professor of medicine and epidemiology, and chief of rheumatology, at the University of Pennsylvania, told attendees. “It behooves us to listen to trials, but they are not the be-all and end-all. You have to be careful how you interpret them.”
Because untreated patients can experience loss of vision and other serious complications, Merkel stressed that the ramifications of failing to diagnose, and treat, in a timely manner can be very serious.
Although Merkel acknowledged the flaws associated with glucocorticoid therapy — including osteoporosis, infections, weight gain and diabetes mellitus — he stressed that steroids should be initiated immediately upon suspicion of GCA.
“The thing to remember about glucocorticoids in GCA is that they work, right up until the complications take hold,” he said. “They are the best drugs we have, and they are the worst drugs we have.”
Perhaps the most important point about steroids is that if there is no dramatic response within 2 to 7 days, the patient “probably” does not have GCA, according to Merkel.
“You need to reconsider the diagnosis,” he said.
Increasingly, clinicians will initiate tocilizumab (Actemra, Genentech) or methotrexate at the time of diagnosis, particularly if the patient demonstrates severe disease.
“Tocilizumab is often the first choice,” Merkel said. “If is not as severe a presentation, you might not start as aggressively.”
The goal, ultimately, is to get the patient off of steroids, according to Merkel.
“Tapering should be done over months, not years,” he said. “Tocilizumab allows you to feel comfortable about tapering more quickly. The days of keeping patients on glucocorticoids for a year are going away.”
Beyond tocilizumab, encouraging data have also been reported for abatacept (Orencia, Bristol Myers Squibb), which has one randomized, controlled trial demonstrating efficacy to its credit. Another is underway, according to Merkel.
Trials have also been initiated for guselkumab (Tremfya, Janssen), secukinumab (Cosentyx, Novartis) and upadacitinib (Rinvoq, Abbvie) in GCA.
“There are lots of agents under study,” Merkel said.
Conversely, clinical trial findings have shown that TNF blockade may not be effective in GCA, he added.
A final question pertains to the potential use of combination therapies.
“Perhaps,” Merkel offered as an answer. “There will be several mechanisms that will be tested and have positive results for this disease.”
Turning to Takayasu arteritis, Merkel acknowledged that there is “much less data” from which to draw conclusions. That said, a wide array of drugs have been used to varying degrees of effectiveness in the Takayasu setting, including methotrexate, TNF inhibitors, tocilizumab, cyclophosphamide, rituximab (Rituxan, Genentech), secukinumab (Cosentyx, Novartis) and tacrolimus, among others, he added.
“We are most confident in the use of methotrexate, TNF inhibitors and tocilizumab,” Merkel said.
Although TNF inhibitors are not recommended for GCA, the situation is different for Takayasu’s arteritis.
“We feel pretty comfortable that TNF inhibition is effective in this disease,” he said.
The key study of tocilizumab in Takayasu arteritis was conducted in 2017, Merkel said, stressing that more data are necessary.
“Do we use it? We do,” he said. “Do I have great confidence? Some.”
Despite the dearth of data, Merkel stated he is “confident and optimistic” that more options for managing patients with Takayasu arteritis will be available in the coming years, for one important reason.
“It is hard to image a group that will hate you more if you put them back on glucocorticoids than patients with Takayasu arteritis,” he said.
As researchers continue to build the evidence base for treatments of these two diseases, Merkel offered an ambitious objective.
“We should be thinking cure,” he said. “I do not think it is going to happen tomorrow, but that should be our goal.”
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Merkel P. Large-Vessel Vasculitis in 2023. Presented at The Congress of Clinical Rheumatology West; Sept. 7-10, 2023 (hybrid meeting).
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