Patients with ANCA-associated vasculitis remain ‘soaked in steroids’ despite new therapies
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DESTIN, Fla. — Despite advances in biologic therapies, “excess steroid use” remains a mainstay of treatment for patients with ANCA-associated vasculitis, according to a presenter at the 2023 Congress of Clinical Rheumatology-East.
“With ANCA-associated vasculitis, we usually win in the short run, but in the longer game, we usually lose,” John Stone, MD, MPH, director of clinical rheumatology and Edward A. Fox Chair in Medicine at Massachusetts General Hospital, and professor of medicine at Harvard Medical School, told attendees.
The focus of Stone’s presentation was how therapeutic approaches have changed in recent decades. He framed the discussion using a patient named David who arrived in his clinic in the early 2000s.
In 2002, the main question was whether to administer cyclophosphamide daily or intermittently. Since then, several therapies have been used to treat ANCA-associated vasculitis, including plasma exchange, azathioprine, avacopan (Tavneos, Amgen) and rituximab (Rituxan, Genentech).
Regarding plasma exchange, Stone noted that the PEXIVAS trial was the largest trial ever done with this approach in ANCA-associated vasculitis. However, the result failed to demonstrate a clear answer on its efficacy.
“The role of [plasma exchange] remains unclear,” he said. “The utility of plasma exchange, if any, is seen very early [in disease course].”
In 2010, Stone and colleagues conducted the RAVE trial, comparing cyclophosphamide with rituximab. “The primary endpoint required prednisone to be tapered completely in 5.5 months,” he said.
Results showed that just 53% of patients in the cyclophosphamide group reached the primary outcome. “Cyclophosphamide is not as good as we once thought it was,” Stone said.
The emergence of rituximab in rheumatology led Guillevin and colleagues to compare it with azathioprine in a 2014 paper in the New England Journal of Medicine. Results showed that rituximab bested azathioprine in disease flares over 28 months (HR = 0.18; P < .0001). “The trial was a resounding success,” Stone said. “Rituximab became the standard of care both for remission induction and remission maintenance.”
The utility of rituximab in ANCA-associated vasculitis “seemed great until COVID,” according to Stone. “It probably brought a wake-up call that we were overdue to have.”
The wake-up call pertained to the thinking about B-cell depletion. “COVID taught us that continuous B-cell depletion is a bad idea and that we need to be thinking about alternatives,” he said.
The good news is that this thinking brought about “the most current breakthrough approach” in avacopan, a C5a receptor inhibitor. “This marks a very important step forward as an adjuvant therapy for the treatment of ANCA-associated vasculitis,” Stone said.
The critical benefit of avacopan pertains to the glucocorticoid toxicity index, according to Stone. Findings from the ADVOCATE trial, which compared avacopan with prednisone, showed that the two approaches were comparable in terms of efficacy. “Where the treatments did differ was in steroid toxicity” by 13 weeks, he said.
Near the end of his presentation, Stone discussed how he would treat his patient David if he walked into the clinic for the first time today.
“I would treat him with rituximab and avacopan as soon as possible,” he said. “I would use lots of steroids at the beginning. Make no mistake, it is important to use lots of steroids to control disease activity early on.”
However, the hope would be that avacopan would allow for the tapering and, ultimately, the elimination of steroid use by the 3-month mark. “Avacopan is not a replacement for steroids, but it is an important adjunct therapy,” Stone said.
In today’s world, cyclophosphamide or plasma exchange would not fit into Stone’s treatment paradigm.
Regarding the ongoing use of rituximab, Stone would consider the patient’s COVID-19 and shingles vaccine status before prescribing another dose.
“In the COVID era, maintenance remains a big question,” Stone said. “The ADVOCATE trial did not give us an answer beyond 1 year.”
Stone concluded that advances in research have benefited this complex patient population. “Targeted biologic therapy has greatly improved outcomes for ANCA-associated vasculitis,” he said. “The next big goal is really to eliminate excess steroid use that our patients still receive. Our patients are still soaked in steroids.”
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Stone J. Update on ANCA-Associated Vasculitis: How Have New Therapies Changed Induction and Maintenance? Presented at: Congress of Clinical Rheumatology-East annual symposium; May 4-7, 2023.
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