AAV treatment is focused on preventing organ damage, managing inflammation, and suppressing parts of the immune system. The goal is to put the vasculitis into remission (where there are no more signs and symptoms), and then to maintain remission.
The choice of treatment depends on the AAV subtype, the severity of your symptoms, and the type of ANCA found on blood tests. There are two main types of ANCA, and you may have one, none, or both:
- cANCA, which targets a protein called proteinase 3 (PR3)
- pANCA, which targets a protein called myeloperoxidase (MPO)
“GPA is more commonly associated with c-ANCA, or PR3 positivity, whereas MPA is associated with p-ANCA, or MPO positivity. EGPA can be ANCA-negative, but when it’s positive, it’s usually associated with p-ANCA (MPO positivity),” says Dua.
“Generally, at the time of diagnosis, distinguishing between GPA and MPA is not essential, as treatment is identical for the 2 conditions,” says Dr. Warrington. “On the other hand, EGPA may require a different treatment regimen targeting the eosinophil.
Treatment Across Subtypes
In ANCA-associated vasculitis, disease severity helps guide treatment decisions, says Warrington. “For instance, when a patient with GPA presents with only sinonasal disease, this scenario is categorized as non-severe disease due to the limited organ involvement,” he says. “But if a patient with EGPA develops what is called mononeuritis multiplex — a condition characterized by damage to multiple nerves — this situation is classified as severe disease.”
The most commonly prescribed medications, used across subtypes, include:
- Corticosteroids These are anti-inflammatory medications that may also suppress the immune system.
- Monoclonal Antibodies These medications are used to treat certain types of autoimmune disorders and cancer, and are often prescribed together with corticosteroids. Rituximab is a type of monoclonal antibody used as a first-line therapy to induce remission, and also for maintaining remission in patients with severe GPA and MPA.
- Chemotherapy Cyclophosphamide is a type of chemotherapy medication that is used to treat certain cancers and autoimmune conditions. Its use is similar to that of rituximab, and is used together with corticosteroids to achieve remission. But rituximab generally has fewer and less-serious side effects, and professional guidelines recommend it over cyclophosphamide for remission induction in many cases.
- Other Immunosuppressants Methotrexate is used in non-severe GPA, while azathioprine is used as a standard maintenance agent. Mycophenolate mofetil is often used as a third-line or alternative maintenance option.
Treatment of GPA and MPA
In severe GPA and MPA, high doses of steroids are used in addition to immunosuppression with rituximab or cyclophosphamide as first-line. Additional therapy with avacopan, a relatively new immunosuppressant drug, may also be considered.
“Rituximab is then typically used as a maintenance therapy, with serial infusions every 6 months for a period of time to keep patients in remission,” says Lally. “In EGPA, patients often need longer courses of steroids than GPA/MPA and this is partially due to a dearth of studies in EGPA looking at different doses of steroids.”
Treatment of EGPA
EGPA treatment also follows a two-stage approach: inducing remission and maintaining it. But EGPA treatment generally requires a different strategy, as the focus is on managing asthma and high eosinophil levels. Recently, there have been significant developments and studies targeting the pathophysiology of EGPA, leading to new approvals for medications specific to EGPA, says Dua.
“In EGPA, we have come a long way … with approvals for mepolizumab and benralizumab for patients with non-severe EGPA,” says Dua. “There is clear evidence demonstrating the ability of [these drugs] to help decrease glucocorticoid use and effectively control many manifestations of EGPA, including persistent asthma, rhinosinusitis, nasal polyposis, nerve involvement, and various other features of the disease.”
Both mepolizumab and benralizumab received approval from the U.S. Food and Drug Administration (FDA) specifically for EGPA to target eosinophils. These agents are not used for standard GPA/MPA treatment. “As we continue to use these types of medications and study them further, I believe we will continue to find more roles for them to help control multiple aspects of active EGPA,” says Dua.
For severe cases of EGPA, treatment still includes corticosteroids combined with cyclophosphamide or rituximab.
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