Growing armamentarium means ‘we have options’ for ANCA-associated vasculitis
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A growing therapeutic armamentarium for antineutrophil cytoplasmic antibody-associated vasculitis — including avacopan and azathioprine — is providing rheumatologists with an increasingly robust array of options, according to a presenter.
“This is a complicated disease,” Peter A. Merkel, MD, MPH, professor of medicine and epidemiology, and chief of rheumatology, at the University of Pennsylvania, in Philadelphia, told attendees at the 2024 Association of Women in Rheumatology annual conference. “If you look for badness you will find it. There is a lot going on in our patients.”
Accordingly, treatment paradigms are complicated and variable from patient to patient, he added. Although glucocorticoids remains the mainstay to control the disease upon initial diagnosis, subsequent interventions may include methotrexate, rituximab (Rituxan, Genentech), azathioprine, cyclophosphamide or avacopan (Tavneos, Amgen).
Although the potential use — alone or in combination — of these interventions can be daunting for some clinicians, Merkel sees this as a positive, noting that prednisone and cyclophosphamide were the only choices for decades.
“This means we have options,” he said.
For patients with non-severe disease who have just been diagnosed, the first step is glucocorticoids, according to Merkel. However, the goal should be to taper patients to a low dose of these medications, or off them entirely, as soon as possible, he added.
“Next, go to methotrexate,” Merkel said. “Start at a low dose and increase. Go fast and go up.”
Meanwhile, some clinicians will reach for rituximab as the first glucocorticoid-sparing agent, according to Merkel.
“This is reasonable for non-severe cases or relapses,” he said.
For patients with severe disease, again, glucocorticoids represent the first line.
“Next is cyclophosphamide or rituximab,” Merkel said.
Although Merkel suggested that he is “not a fan” of using cyclophosphamide and rituximab together, other combinations with cyclophosphamide may be effective.
“With cyclophosphamide, you can do these other things,” he said. “There is good data to support continuing with azathioprine or methotrexate, or mycophenolate as a third choice.”
According to Merkel, rituximab alone is gaining momentum as the “next obvious choice” as a glucocorticoid sparing agent, even before cyclophosphamide, methotrexate and other agents.
“It just works better,” he said.
Meanwhile, although there are less data for the C5A inhibitor avacopan, Merkel suggested that findings from the ADVOCATE trial, which compared avacopan with prednisone, support a future for this agent in ANCA-associated vasculitis.
“What we found is that there were fewer relapses in the avacopan group, much less glucocorticoid use, much less glucocorticoid toxicity, better quality of life improvement, and better renal improvements,” he said.
Although Merkel acknowledged some safety signals with the medication, he added that using it according to ADVOCATE trial protocols could minimize infectious and other events. “Use it up front, and use it quickly,” he said.
Lastly, regarding chimeric antigen receptor (CAR) T-cell therapy — which has seen a deluge of promising data across a host of autoimmune and rheumatic diseases — Merkel noted that he works at the University of Pennsylvania, where the approach “was invented.”
Despite his enthusiasm for CAR T-cell therapy in ANCA-associated vasculitis and other conditions, he counseled caution.
“I would like to remind you that this is an experiment and that we have not proven anything yet,” Merkel said. “I do not want to give patients a therapeutic misconception.”
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Merkel P. Update on Treatment of ANCA-Associated Vasculitis Presented at: Association of Women in Rheumatology annual conference; July 25-27, 2024; Orlando, Florida (hybrid meeting).
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