Relapse Risk Lower When ANCAs Are Undetectable, Study Finds

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Undetectable blood levels of ANCAs within six months of remission induction treatment were associated with a lower risk of relapses over the next five years in people with ANCA-associated vasculitis (AAV), a study showed.

The presence or absence of disease-causing antibodies did not seem to impact the risk of end-stage kidney disease or death.

The study, “The effect of achieving serological remission on subsequent risk of relapse, end-stage renal disease and mortality in ANCA-associated vasculitis: a target trial emulation study,” was published in Annals of the Rheumatic Diseases. 

AAV patients have circulating ANCAs, or anti-neutrophil cytoplasmic autoantibodies, that are responsible for the autoimmune disease’s symptoms. Testing for these ANCAs has long been a central component to diagnosing AAV.

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After diagnosis, patients are usually given treatments aimed at inducing disease remission. While most achieve clinical remission, that is, they stop experiencing symptoms, only a portion have undetectable ANCA blood levels, or achieve serological remission.

The clinical relevance of ANCA blood levels after remission induction remains poorly understood, and the use of ANCA testing to monitor disease activity is controversial.

Researchers in the U.S. created a hypothetical clinical trial by analyzing ANCA levels and outcome data from AAV patients included in the Mass General Brigham AAV cohort. This type of approach employs statistical techniques that prevent biases often present in observational studies, the researchers said.

Their goal was to evaluate the long-term clinical effects of achieving serological remission within 180 days (six months) of remission induction. In particular, researchers were interested in knowing whether undetectable ANCAs affected a later risk of relapse, end-stage kidney disease, or death.

According to the team, the six-month time point was chosen because it usually marks the end of the remission induction phase, and a transition to maintenance therapies.

“Achieving a negative ANCA assay at this time may have prognostic significance and inform the choice and intensity of maintenance therapy or subsequent monitoring by identifying patients with favourable AAV treatment response and low risk of subsequent relapse,” the research team wrote.

Included in the mimicked trial were 506 patients (58% female) with a mean age of 61. Most patients were white (87%) and had ANCAs of the myeloperoxidase (MPO) type (72%).

At the study’s start, most had some type of major organ involvement (78%), usually the kidneys (68%).

Remission induction treatment included rituximab in 59% of cases, with 33% receiving cyclophosphamide and the remaining 8% receiving other treatments. Some patients (24%) also received plasma exchange therapy.

The mean number of ANCA measurements taken in the first 180 days after remission induction was 3.5. In the analysis, it was determined that 122 people achieved serological remission during that time with no detectable ANCAs in their blood tests.

Within five years, 81 people had died (16%), 51 (10%) had end-stage renal disease, and 64 (13%) relapsed. The median time to death was 675 days (1.8 years), to end-stage renal disease was 33 days (one month), and to relapse was 539 days (about 1.5 years).

Serological remission within six months of remission induction was associated with a significantly reduced risk of relapse. Specifically, the five-year incidence of relapse was 9.4 per 100 people with serological remission and 18.3 per 100 people in those without it.

In subgroup analyses, serological remission was similarly linked to a significant reduction in the risk of relapse among patients who were MPO-positive at the study’s start and those treated with rituximab. Serological remission was not associated with the risk of end-stage kidney disease or death.

“These findings suggest that achieving a negative ANCA assay during and after induction may result in fewer subsequent disease relapses,” the researchers wrote, noting more studies are needed to see how “postinduction ANCA titres and other disease biomarkers may guide AAV management strategies.”