3 Factors Identified that May Predict Relapses Within 5 Years of AAV Diagnosis

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by Somi Igbene |

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A positive anti-proteinase 3 (PR3) ANCA test, lower serum creatinine levels, and cardiovascular involvement at diagnosis appear to raise the risk of relapse in people with ANCA-associated vasculitis (AAV), a review study reports.

When combined, these factors may predict an individual’s risk of relapse within five years after diagnosis, though more studies are needed to test all three factors and search for additional predictors of relapse.

The study, “Predicting relapse in anti-neutrophil cytoplasmic antibody-associated vasculitis: a systematic review and meta-analysis,” was published in Rheumatology Advances in Practice.

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Although people with AAV initially achieve disease control with immunosuppressive therapies, around 30–50% of patients relapse within five years, needing repeat courses of these harmful and potentially life-threatening therapies.

Reducing relapses by achieving and maintaining remission is, therefore, essential to minimize exposure to immunosuppressive therapies.

One way to reduce relapses is to identify the risk factors that predict them. So far, studies investigating relapse risk factors in AAV have produced varied results, and no further studies have assessed the reliability of the identified risk factors in predicting relapses in individuals.

To learn more, a team of scientists at the University of Birmingham in the U.K. conducted a comprehensive literature search to identify risk factors for relapse in AAV. They also sought to develop a model to predict relapse risk in individuals with AAV in real-life settings.

After searching in MEDLINE and EMBASE databases from their inception to December 2020, the researchers identified a total of 2,674 published studies. Upon further evaluation, 16 studies published between 2005 and 2018, including 2,785 participants, were eligible for analysis.

A total of 30 risk factors were identified in the 16 studies. However, after analysis, only three risk factors — a positive test anti-PR3 ANCA antibodies, cardiovascular system involvement, and low serum creatinine at diagnosis — were significantly associated with relapse risk in people with AAV.

In particular, results showed that the risk of relapse was 69% greater in people who tested positive for anti-PR3 antibodies at diagnosis, and 78% higher in the presence of cardiovascular symptoms.

On the other hand, patients whose creatinine levels were above 200 micromoles per liter (umol/L) — indicative of severe kidney problems — were 61% more likely to experience a relapse than patients with levels of 100 or lower. Those whose levels ranged from 101 to 200 also had a 19% higher risk of relapse.

These three risk factors were then combined to develop a predictive model of relapse risk.

To develop and validate the model, the researchers used data from 182 participants with AAV. Patients had a median of 57 years, 58% were male, and 89% were white British. At diagnosis, a total of 61% had a positive anti-PR3 test, and 6% had cardiovascular system involvement.

Creatinine levels are often used as a proxy of kidney function. The normal range for men ranges from 61.9–114.9 umol/L for men and 53–97.2 umol/L for women. The median creatinine for this group was 146 umol/L, indicating mild kidney abnormalities.

At diagnosis, 33% of patients had a creatinine levels of 100 umol/L or less, 32% had 101–200 umol/L ,and 35% greater than 200 umol/L.

Using the model, the researchers found that people with positive anti-PR3 ANCA and preserved renal function at diagnosis had the greatest risk of relapse. Because the incidence of cardiovascular involvement was minimal, the researchers could not reliably assess its contribution to relapse risk.

“Clinicians, when presented with patients with both risk factors, must consider a prolonged duration of maintenance therapy, but a model based around only two factors is unlikely to be clinically useful,” the researchers wrote.

Future studies should identify more risk factors to develop a clinically useful model that categorizes risk factors and guides the duration of maintenance therapy.

Still, the current study shows that anti-PR3 positivity, lower serum creatinine, and cardiovascular involvement at diagnosis increase relapse risk, and combining at least two of these risk factors may predict an individual’s risk of relapse.