Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) encompasses a group of rare autoimmune diseases characterized by inflammation of small and medium-sized blood vessels. These conditions – granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA) – can affect multiple organs, leading to potentially life-threatening complications. Treatment focuses on suppressing the immune system to prevent organ damage and achieve remission.
Understanding AAV Subtypes and ANCA Markers
The approach to AAV treatment is guided by the specific subtype of the disease, the severity of symptoms, and the presence of certain antibodies known as ANCA. There are two main types of ANCA: cytoplasmic ANCA (cANCA), which targets proteinase 3 (PR3), and perinuclear ANCA (pANCA), which targets myeloperoxidase (MPO). GPA is more frequently associated with cANCA positivity, while MPA is typically linked to pANCA. EGPA can be ANCA-negative, but when present, it’s usually associated with pANCA.
Distinguishing between GPA and MPA at the time of diagnosis isn’t always essential, as initial treatment is often the same for both. However, EGPA may require a different treatment strategy focused on managing eosinophil levels.
Treatment Strategies: Induction and Maintenance of Remission
Treatment for AAV generally follows a two-stage approach: inducing remission – eliminating active signs and symptoms – and maintaining remission to prevent relapse. Disease severity is a key factor in determining the appropriate treatment plan.
Commonly prescribed medications used across AAV subtypes include corticosteroids, monoclonal antibodies, chemotherapy, and other immunosuppressants. Corticosteroids are anti-inflammatory drugs that also suppress the immune system. Rituximab, a monoclonal antibody, is often used as a first-line therapy to induce remission and for maintaining remission in severe cases of GPA and MPA. Cyclophosphamide, a chemotherapy medication, is also used to achieve remission, often in combination with corticosteroids, but rituximab is generally preferred due to a more favorable side effect profile.
Other immunosuppressants, such as methotrexate and azathioprine, play a role in managing AAV. Methotrexate is used in non-severe GPA, while azathioprine is a standard maintenance agent. Mycophenolate mofetil can be used as a third-line or alternative maintenance option.
Specific Treatment Approaches for GPA and MPA
For severe GPA and MPA, high doses of corticosteroids are typically used alongside immunosuppression with either rituximab or cyclophosphamide. A newer immunosuppressant drug, avacopan, may also be considered as an adjunctive therapy. Avacopan was approved by the FDA after the 2021 ACR/VF guidelines were written and may help reduce exposure to glucocorticoids.
Following remission induction, rituximab is often used as a maintenance therapy, administered through serial infusions every six months to sustain remission.
EGPA Treatment: A Targeted Approach
EGPA treatment also involves induction and maintenance of remission, but often requires a different strategy. The focus is on managing asthma and elevated eosinophil levels. Recent advancements and studies targeting the underlying mechanisms of EGPA have led to the approval of new medications specifically for this condition.
Mepolizumab and benralizumab, both approved by the U.S. Food and Drug Administration, are used for non-severe EGPA. Evidence demonstrates their ability to decrease corticosteroid use and effectively control various EGPA manifestations, including persistent asthma, rhinosinusitis, nasal polyposis, and nerve involvement.
For severe cases of EGPA, treatment still involves corticosteroids combined with cyclophosphamide or rituximab.
The Importance of Guidelines and Ongoing Research
The American College of Rheumatology and the Vasculitis Foundation published guidelines in 2021 for the management of AAV. The British Society for Rheumatology (BSR) also released updated recommendations in August 2025, building upon previous guidelines and incorporating findings from numerous randomized controlled trials and research studies. These guidelines aim to provide healthcare professionals with evidence-based recommendations for treating these complex diseases.
Ongoing research continues to refine treatment strategies and improve outcomes for individuals living with AAV, particularly in subtypes like EGPA where new therapeutic options are emerging.
