Researchers Call for New System to Better Classify Vasculitis

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A new classification system, based on the underlying cause of disease, may be necessary to better understand ANCA-associated vasculitis (AAV) and other disorders characterized by inflammation in the blood vessels.

That’s according to a team led by scientists at Aarhus University, in Denmark, who published their idea for the new system in a paper titled “Vasculitis therapy refines vasculitis mechanistic classification,” in Autoimmunity Reviews.

AAV is an umbrella term covering three different conditions: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA).

These conditions are grouped together because they all are forms of small vessel vasculitis — that is, inflammation that affects the smaller blood vessels in the body.

The most common methods for classifying vasculitis (blood vessel inflammation) are based on the types of blood vessels that are affected. But according to the researchers, such a classification system ignores the underlying cause of disease.

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“Some of the diseases that were previously classified as being very similar, actually turn out to be quite different,” Christopher Kirkegaard Torp, a researcher at Aarhus and a study co-author, said in a press release.

“They affect the same kind of blood vessels but there are significant differences in the response to different treatments,” Torp said.

More and more highly targeted immunological treatments have been tested in vasculitis in recent years. Here, researchers conducted a review of 40 previously published studies — including 20 randomized controlled clinical trials — covering treatments of AAV and other kinds of vasculitis.

Their goal was to analyze which treatments were effective, and which were not, so as to learn more about the underlying cause of the diseases.

“We’re dealing with a group of immune mediated inflammatory diseases that must be treated in very different ways,” said Tue Wenzel Kragstrup, a professor at Aarhus and also a study co-author.

“We’ve made so much progress with the clinical trials now that we can use them to learn about understanding of diseases and the underlying immunology,” Kragstrup said.

The results showed that the medication rituximab “has proven to be an effective treatment option for both newly diagnosed, relapsing and refractory GPA and MPA,” the researchers wrote.

Rituximab works mainly by killing immune cells called B-cells. These cells are responsible for producing antibodies, including the self-targeting ANCAs — anti-neutrophil cytoplasmic autoantibody — that drive most cases of AAV.

While the efficacy of rituximab in GPA and MPA is well-established, much less is known about its effectiveness in the third type of AAV, EGPA. Indeed, the researchers noted that studies of rituximab and other B-cell-killing therapies “only includes case reports, retrospective studies and a single prospective cohort study.”

They also noted emerging data that suggest that EGPA patients who are positive for ANCA might respond markedly better to rituximab than those who are not positive for these disease-driving antibodies.

Another treatment that has shown promise in GPA and MPA is Tavneos (avacopan), which was recently approved in the U.S. and Japan. This medication works by blocking a part of the immune system called the complement cascade.

Tavneos has never been tested in EGPA, so it’s unknown whether or not it is effective in this type of AAV.

However, therapies that block interleukin-5 (IL-5) have shown promise for EGPA, the researchers wrote. IL-5 is a signaling molecule that’s particularly important for the activation of eosinophils, which are a kind of immune cell known to play a central role in the development of EGPA.

Collectively, these data highlight that, even though they affect the same kinds of blood vessels, the biological processes that drive MPA and GPA may be quite distinct from those that cause EGPA.

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“Especially ANCA negative EGPA seems to be immunologically very different from GPA/MPA,” the researchers wrote. “Therefore, in an immunology-based classification based on current evidence, it would make sense to separate EGPA from GPA/MPA.”

Researchers in Spain also have called for a new classification system. In a 2019 study, these researchers called for an improved classification system that could better predict disease outcomes.

Here, the team also noted some similar differences among diseases characterized by inflammation of large blood vessels. They stressed the need for more research to understand the mechanisms that drive these diseases.

“Once you know the cause of a disease, it becomes easier to develop new medicines or test existing drugs for the disease in question,” Kragstrup said.

Having a new classification system based on cause would aid in such efforts, he said.

Such a system would “help patients, doctors and researchers to a better understanding and thereby better treatment,” Kragstrup said, adding that a new classification “paves the way for clinical trials with other drugs targeting adjacent immunological abnormalities to identify new treatment options for the patients.”