Treatment options for two of the most refractory forms of ANCA-associated vasculitis are improving. Accumulating observational data and new randomized controlled trials are identifying more targeted strategies and therapies to minimize toxicity and improve outcomes in granulomatosis with polyangiitis/microscopic polyangiitis (GPA/MPA) and eosinophilic granulomatosis with polyangiitis (EGPA).
“This is a very exciting time as better therapies are being developed and as we are better understanding our existing therapies,” said Sharon A. Chung, MD, MAS, associate professor of clinical medicine, University of California, San Francisco, and director, UCSF Vasculitis Clinic. “We are already seeing improved outcomes and will have better outcomes coming in the future.”
Dr. Chung outlined the latest treatment approaches in GPA/MPA and EGPA during State of the Art: Treatment of ANCA-Associated Vasculitis in 2020. Dr. Chung’s presentation and question-and-answer session will be available on demand for registered ACR Convergence 2020 attendees through Wednesday, March 11.
The general treatment strategy for severe GPA/MPA still begins with remission induction for three to six months, followed by remission maintenance therapy, Dr. Chung noted. Approaches to both are evolving.
Rituximab and cyclophosphamide remain the primary agents in remission induction. Experience suggests that rituximab is preferable due to better tolerability. Cyclophosphamide has fewer side effects but greater potential for relapse.
The PEXIVAS study of adjunctive plasma exchange vs. no plasma exchange with standard or reduced-dose glucocorticoids has added new possibilities for remission induction. The study found no improvement in mortality or end stage kidney disease, the primary outcome, after a mean follow-up of 2.9 years. But an ACR guideline development team working on a new clinical guideline for AAV included PEXIVAS in a meta-analysis and found a hazard ratio of 0.61 favoring plasma exchange for developing end stage kidney disease.
“Consider plasma exchange for patients at highest risk for end stage renal disease, those with a creatine of 3.4 mg/dL and higher,” Dr. Chung advised.
PEXIVAS also found no difference in mortality and end stage kidney disease by glucocorticoid dose. But reduced glucocorticoid dosing carried a hazard ratio for 0.69 for serious infections at one year.
“We are still finding our way with plasma exchange,” Dr. Chung said. “With end stage kidney disease, the data are a little clearer. You are justified in doing plasma exchange.”
There is also growing data suggesting that glucocorticoids may be dropped, not just reduced. ADVOCATE, a phase 3 randomized clinical trial of avacopan in place of glucocorticoids, found that avacopan is non-inferior to prednisone at week 26 and superior to prednisone at week 52.
“We already know that reduced glucocorticoids is not inferior to standard dosing and reduces the risk of infection,” Dr. Chung said. “If we stopped using glucocorticoids altogether, I don’t think any of my patients would protest.”
There is also evidence that remission might be maintained longer than the six months seen in most clinical trials. MAINRITSAN3 found that rituximab can maintain remission up to 28 months in 91% to 100% of patients. Prolonged rituximab may be appropriate for patients at high risk for relapse.
Less is known about the effects of rituximab in EGPA, Dr. Chung noted.
There are not strong randomized clinical trial data, but clinical experience and observational data suggest that biologics may help some patients. Rituximab is not completely steroid sparing in EGPA, and asthma flares are still noted, but the agent may be useful in severe disease.
For non-severe disease, mepolizumab may be more effective than omalizumab. Other anti-IL-5 agents are being investigated.