ANCA-associated vasculitis (AAV) groups together three rare autoimmune conditions: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). In the past, AAV was often fatal. But treatment today — the specifics of which differ between the three types — has changed that.
“Thanks to many advances over the last few decades, we are able to get the disease under control in the majority of patients,” says pulmonologist Lynn Fussner, MD, a vasculitis researcher and the co-director and pulmonary lead of the Multidisciplinary Vasculitis Clinic at The Ohio State University Wexner Medical Center in Columbus.
ANCA stands for “anti-neutrophil cytoplasmic antibodies.” Made by your immune system, autoantibodies cause white blood cells called neutrophils to attack healthy small blood vessels throughout your body. This leads to damaging inflammation, often in multiple organs, such as your kidneys, lungs, skin, sinuses, eyes, and more.
Fortunately, AAV can be managed with medications, allowing people with the condition to live longer, more comfortable lives while researchers pursue a permanent remedy.
“Over the course of time, we’ve seen many advances that we know will continue as we work towards the goal of a cure,” says rheumatologist Carol Langford, MD, the director of the Center for Vasculitis Care and Research at Cleveland Clinic in Cleveland, Ohio.
How Treatment Has Evolved Over the Years
Until about 50 years ago, an estimated 4 out of 5 people with AAV would die within a year of diagnosis if left untreated. Doctors couldn’t count on medications used decades ago to delay the inevitable, even temporarily.
“That really changed in the 1970s,” Langford says.
That’s when a combination therapy of two drugs proved effective. Those drugs were:
Cyclophosphamide (Cytoxan). This chemotherapy drug is used to treat certain types of cancer. It suppresses the immune system, which reduces inflammation causing tissue injury.
Prednisone. This is a type of steroid (also called a glucocorticoid). It also suppresses the immune system.
“[That combination] made this a treatable disease in which patients can have long-term survival and good quality of life,” Langford says.
This combination is still in use today. But in 2011, a newer medication called rituximab (Rituxan) was approved by the FDA to treat GPA and MPA. It’s also sometimes used off-label for EGPA. Rituximab is a type of drug called a monoclonal antibody, and it specifically targets and depletes cells that make antibodies. These days, it’s prescribed more often than cyclophosphamide.
What Are the Goals of AAV Treatment?
Your doctor will aim to improve your symptoms and prevent permanent organ damage by suppressing your immune system and controlling inflammation. Your doctor may refer to this as getting your AAV into remission.
“Remission is a very general term which indicates that there is no evidence of active inflammation that is causing organ, tissue, or blood vessel injury,” Langford says.
Treatment has two phases:
- Induction, in which you take medications to achieve remission
- Maintenance, in which you take medications to stay in remission
Induction
During this phase, if you have severe AAV, you may be prescribed rituximab or cyclophosphamide along with high doses of prednisone.
“Rituximab or cyclophosphamide are typically used for severe disease, which may be organ- or life-threatening and/or involve multiple organ systems at once,” Fussner says.
Other medications may be used during induction for non-severe AAV, such as the immunosuppressant medications methotrexate (Rheumatrex, Trexall, Xatmep) or mycophenolate mofetil (CellCept), Langford says.
The induction phase lasts an average of three months. But it depends on the case.
“Some people may achieve remission in the first month, and for some, it may take longer than three months,” Langford says.
During this time, your doctor likely will slowly reduce your dose of steroids to prevent side effects that can occur when these drugs are taken for long periods. Such side effects include:
- Infections
- Weakened bones and bone breaks
- Thinning skin
- Weight gain
- Mood changes
- Increased blood pressure and blood sugar
Maintenance
During this phase, you may discontinue prednisone but remain on rituximab or another medication to keep your AAV from coming back, or relapsing. For how long? That varies from person to person, but in general, Langford says she wants her patients to remain free of active inflammation for at least two years before discussing next steps.
“At the end of that period of time, together with the patient, we make a decision about whether we make any changes in treatment or continue with what we’re doing,” Langford says.
If your disease does relapse and symptoms return, you’ll return to the induction phase of treatment to get it under control again, followed by the maintenance phase.
“Unfortunately, by nature, the [three types of AAV] tend to be relapsing diseases,” Langford says.
Other drugs your doctor may consider during the maintenance phase include the immunosuppressant azathioprine (Azasan, Imuran), methotrexate, or mycophenolate mofetil. Though not as effective as rituximab, they may be used if you can’t take rituximab for any reason, such as a drug allergy, says Fussner.
What Are the Latest Treatment Advances for AAV?
In 2021, the FDA approved a drug called avacopan (Tavneos) for severe AAV. This was a big step forward because it allows people with this condition to achieve remission while quickly reducing the initial high dose of glucocorticoids like prednisone during the induction phase.
“Those higher doses of prednisone are where we tend to see the most side effects and impacts on patient quality of life,” Langford says.
Avacopan targets a part of your immune system called the complement system. The complement system consists of proteins that protect you when you get injured or are at risk of infection from bacteria or another invader. These complement proteins get activated one after another in what’s called a cascade. Avacopan blocks a particular protein in this cascade called C5a, which promotes inflammation.
Avacopan has been approved only for the induction phase of treatment in people with severe active disease given in combination with either rituximab or cyclophosphamide, says Langford.
There also have been advances in the treatment of EGPA, the least common form of ANCA-associated vasculitis. Treatment for EGPA also involves an induction and maintenance phase, and many of the medications used for EGPA are the same as for GPA and MPA. However, there are differences in treatment, including the use of the following medications:
Mepolizumab (Nucala). This biologic, a monoclonal antibody, was approved by the FDA in 2017. It curbs the production of immune system cells called eosinophils by blocking interleukin-5 (IL-5), an immune system protein. It was the first targeted treatment for EGPA.
Benralizumab (Fasenra). This biologic — also a monoclonal antibody — was approved by the FDA in 2024. It acts on IL-5 as well as on eosinophils directly, leading to their nearly complete depletion.
These drugs are often used in both the induction and maintenance phases of treatment for EGPA, says Fussner.
What Does the Future Hold for AAV Treatment?
There are multiple clinical trials and preclinical studies happening now that are investigating new approaches with available medications, as well as drugs that fight inflammation in new ways, Fussner says. Precision immunotherapies — cell-based therapies that target cells and proteins — are also being studied. They include engineered antibodies with specific targets as well.
“The goal would be to minimize the suppressive effects on the rest of the immune system, of course, but we’re not there yet,” Fussner says.
Some of these precision immunotherapies under investigation aim to engage the immune system in ways similar to immunotherapies used to treat certain cancers.
But it’s too soon to highlight any specific medications now in development, Langford says.
“I don’t want to speculate on what may or may not be effective until we see results in studies, but this is a very active area of investigation,” she says. “We recognize that there remains a long way to go until we have a cure. Our work must continue.”
