Congress of Clinical Rheumatology Annual Meeting

Congress of Clinical Rheumatology Annual Meeting

Source:

Merkel PA. Update on ANCA-Associated Vasculitis. Presented at: Congress of Clinical Rheumatology-West annual symposium; September 18-21, 2021 (hybrid meeting).

Disclosures: Merkel reports consulting for Abbvie, Amgen, Bristol Myers Squibb, Boehringer Ingelheim, ChemoCentryx, CSL Behring, Forbius, Genentech/Roche, GlaxoSmithKline, InflaRx, Janssen, Kiniksa, Magenta, Neutrolis, Novartis, Sanofi, Sparrow and Talaris; receiving research support from Abbvie, Amgen, Bristol Myers Squibb, Biogen, ChemoCentryx, Forbius, GlaxoSmithKline, Genentech/Roche and InflaRx; and receiving royalties from UpToDate.
September 20, 2021
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Three trials offer hope for 'challenging' steroid sparing in ANCA-associated vasculitis

Source:

Merkel PA. Update on ANCA-Associated Vasculitis. Presented at: Congress of Clinical Rheumatology-West annual symposium; September 18-21, 2021 (hybrid meeting).

Disclosures: Merkel reports consulting for Abbvie, Amgen, Bristol Myers Squibb, Boehringer Ingelheim, ChemoCentryx, CSL Behring, Forbius, Genentech/Roche, GlaxoSmithKline, InflaRx, Janssen, Kiniksa, Magenta, Neutrolis, Novartis, Sanofi, Sparrow and Talaris; receiving research support from Abbvie, Amgen, Bristol Myers Squibb, Biogen, ChemoCentryx, Forbius, GlaxoSmithKline, Genentech/Roche and InflaRx; and receiving royalties from UpToDate.
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A trio of recent clinical trials showed encouraging results for steroid-sparing strategies in ANCA-associated vasculitis, according to a presenter at the 2021 Congress of Clinical Rheumatology-West.

“Just to remind you, ANCA-associated vasculitis is an extraordinarily multisystem complex disease,” Peter A. Merkel, MD, MPH, chief of the Division of Rheumatology at the University of Pennsylvania, told attendees. “If you have seen one patient, you have seen one patient. There are all different patterns.”

“Steroid sparing is challenging, but it can be done, and it has been done,” Peter A. Merkel, MD, told attendees. “We are now at a place where we can use less glucocorticoids than we were before.” Source: Adobe Stock

It is for this reason, that there continue to be unmet needs in the disease. “One, we want to spare glucocorticoids,” he said. “We would like to have more cyclophosphamide sparing agents. We need to more rapidly induce remission, and we need to prevent relapsing disease.”

The RITAZAREM, PEXIVAS and ADVOCATE trials have provided hope that some of these needs can be met, according to Merkel.

Peter A. Merkel

In RITAZAREM, Merkel’s group compared rituximab (Rituxan, Genentech) with azathioprine for inducing remission in a cohort of 190 patients. All patients in the trial had relapsed, according to Merkel. “This puts them at much higher risk for relapsing again,” he said.

After pretrial treatment with rituximab, the majority of the cohort went into remission. Patients were then treated with one of the two drugs for 2 years and then followed for an additional 2 years after they went off therapy. Results showed that patients treated with rituximab were less likely to relapse (HR = 0.41; P < .001). “There is pretty good separation in the first 2 years,” Merkel said.

In PEXIVAS, 700 patients with severe disease were randomly assigned cyclophosphamide or rituximab with IV methylprednisolone. There was a standard and reduced dose of the glucocorticoid given as per study protocols, according to Merkel. In addition, patients in each group were randomly assigned plasma exchange or no plasma exchange. “This was a sick group of patients,” he said.

Results showed that 28% of patients in the plasma exchange group and 31% in the no plasma exchange group met the primary outcome of end-stage renal disease or death, according to Merkel. “Clinically and statistically, they were not significantly different,” he said.

Similarly, there was no difference in the primary outcome based on whether patients had received the standard or reduced dose of glucocorticoids. However, Merkel stressed that there was a significant reduction in infections among patients treated with the reduced dose of glucocorticoids compared with the standard dose. "This is what we wanted to see,” he said. “Same level of remission, fewer infections."

In the ADVOCATE trial, Merkel’s group investigated the novel C5a receptor inhibitor avacopan (ChemoCentryx) for patients with moderate to severe vasculitis. “The science tells us that C5a and other complement products are a part of what is going on at the tissue level,” he said. “It is part of what activates neutrophils and causes inflammation and damage.”

All patients had received rituximab or azathioprine, but the study zeroed in on avacopan in 166 patients versus prednisone in 164 patients. That said, all patients received some steroids at some point in the trial as per protocols. Remission at 26 weeks and sustained remission at 52 weeks served as the key endpoints.

“Avacopan was noninferior to glucocorticoids at 26 weeks and superior to the glucocorticoids at 52 weeks,” Merkel said. “However, it is important to understand that it is not no glucocorticoids, but it is a much-reduced glucocorticoid strategy.”

It is for this reason that Merkel arrived at a key conclusion to be drawn from this recent research. “Steroid sparing is challenging, but it can be done, and it has been done,” he said. “We are now at a place where we can use less glucocorticoids than we were before.”