Mortality Risk Is Higher for AAV Patients, Long-term Study Reveals

Older age, worse kidney function cited as key factors in analysis

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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Patients with ANCA-associated vasculitis (AAV) have a higher risk of mortality than the general population, especially those who are older or have impaired kidney function, a long-term outcome analysis study has found.

Infections were the leading cause of death, with treatment complications, such as immunosuppression and blood vessel inflammation, known as vasculitis, identified as major contributing factors.

“Excess mortality rate increases with time, which highlights the importance of the clinical follow up in AAV to monitor disease activity and potential complications,” the researchers wrote. “To our knowledge, this is the largest and most extensive long-term follow up of patients with AAV.”

The findings of the analysis were detailed in the study “Long-term outcomes and prognostic factors for survival of patients with ANCA-associated vasculitis,” published in the journal Nephrology, Dialysis, Transplant.

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Identifying risk factors for mortality in AAV

AAV is a rare group of autoimmune diseases marked by inflammation and damage to small blood vessels, particularly those in the kidneys and lungs. Despite advancements in immunosuppressive therapies, patients can still experience poor outcomes, and predictive factors for long-term survival are not well-defined.

Since 1995, the European Vasculitis Society (EUVAS) has carried out several clinical trials to optimize or compare available treatment options for AAV patients, with the goal of improving outcomes.

Researchers in the U.K. and across Europe have now conducted a long-term outcome assessment of the 848 AAV patients who enrolled in seven of these EUVAS studies: NORAM, CYCAZAREM, MEPEX, CYCLOPS, IMPROVE, RITUXVAS, and MYCYC. All participants were newly diagnosed with AAV at the time of study entry.

“The present study was to assess the long-term patient survival of this unique cohort [group] of patients previously included in EUVAS [studies] and to identify possible prognostic factors,” the researchers wrote.

Before the start of this study, 150 of the original patients had died. Data on the remaining 698 participants were requested via questionnaires sent to the principal investigators of the original studies, and information on 490 (70%) was returned.

Among the original study participants, 478 (56.4%) were diagnosed with granulomatosis with polyangiitis (GPA) and 370 (43.6%) with microscopic polyangiitis (MPA), two common types of AAV. The mean age at diagnosis was 57.5, with a median follow-up of eight years (ranging from 0–24.5 years).

Patients showed signs of impaired kidney function, with a median estimated glomerular filtration rate (eGFR) — a measure of kidney function — of 42.1 mL/min/1.73m2, which is below the normal range of 60 or more. Kidney failure, or an eGFR below 15, was reported in 23.5% of cases.

As a first treatment, 638 patients received cyclophosphamide (sold as Cytoxan), of whom 402 (63%) were treated orally and 236 (37%) by intravenous (into-the-vein) infusion directly into the bloodstream. Those who received IV cyclophosphamide seemed to live longer, the team indicated.

During long-term follow-up, 305 study participants died — a higher mortality rate than a control population matched by country, age, and sex. Among AAV patients, there were 14.2% more deaths at five years, 19.9% at 10 years, 28.8 % at 15 years, and 36.3% more at 20 years.

Excess mortality occurred in AAV patients across all age groups, even in individuals younger than 50, researchers noted.

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Early diagnosis, treatment, ‘likely to improve outcomes’

Statistical estimates indicated the median survival time was 17.8 years after study entry, with a survival rate of 81.2% at five years, 67.6% at 10 years, and 54.2% at 15 years.

Although patients who enrolled later in trials (after year 2000) appeared to live longer than those who enrolled earlier, differences were not considered statistically significant.

Researchers speculated that this trend could be due to increased awareness of AAV among clinicians and/or possible advances in standard therapy regimens. Earlier diagnosis and treatment are “also likely to improve outcomes.”

Regarding location, individuals from northern European countries had lower survival rates and worse kidney function at study entry than those from Western and Southern European countries.

Infections (26%), cardiovascular disease (14%), and cancer (13%) were the primary causes of death for those assessed, followed by lung disease, vasculitis, kidney disease, and digestive tract illness. Cancer was the most common cause of death among youngest patients (22.6%).

Of all deaths, 110 occurred in patients with kidney failure, primarily due to infection. Moreover, the highest number of deaths occurred in those with limited kidney function (low eGFR) at study entry.

Vasculitis was considered a contributing factor in the death of 18.4% of patients, and immunosuppression in 17.4% of the cases.

Factors that predicted poor survival included advanced age, which was associated with a 9.9 times higher risk of death, and low eGFR, which was linked to a 2.63 times higher risk.

Men had a 30% relative increase in mortality risk, as did those with low platelet counts, with a 70% relative increased risk. AAV subtypes did not influence survival, according to the data.

“The conclusions of the study will raise concern about the need for a systematic follow up of patients with AAV in the long term and will also have impact on improved design of future [clinical trials], tailoring therapy to the individual patient with respect to risk factors to prevent eventual side effects such as infections and malignancies,” the researchers concluded.