The mortality rate of patients presenting with severe manifestations of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) was relatively high despite treatment with plasma exchange, according to researchers in Prague.
Among 94 patients, the estimated 1-year and 5-year survival rates were 75.3% and 61.1%, respectively, reported Doubravka Frausová, MD, of Charles University, and colleagues.
The leading cause of death was infection, followed by cardiovascular causes, the authors wrote in Arthritis Research & Therapy, although in 10 patients, the cause of death was unknown or unavailable.
AAV represents a group of autoimmune diseases, most of which are associated with the presence of circulating ANCA.
Plasma exchange (PLEX) has been used routinely to treat severe manifestations of ANCA-associated vasculitis, but there is no evidence supporting its long-term benefits.
However, the ongoing Plasma Exchange and Glucocorticoids for Treatment of ANCA-Associated Vasculitis (PEXIVAS), a multicenter, international, randomized trial, should establish the efficacy of PLEX in reducing death and end-stage renal disease in AAV patients.
"The prognosis of patients with severe ANCA-associated vasculitis has been improving, and plasma exchange is an important part of the therapeutic approach, but until more data is available, the real benefit of plasma exchange is unclear," Frausová told MedPage Today.
The current study was a retrospective analysis of medical records n consecutive patients, treated with at least one membrane PLEX, in a single tertiary referral center from 2000 to 2010.
Researchers assessed active organ involvement using the Disease Extent Index (DEI), which can range from 0 to 21.
PLEX was an adjunctive therapy added to standard immunosuppression. It was performed by using a filter separation technique with the most common PLEX dose including seven PLEX sessions performed within 14 days.
Of the 94 patients identified with AAV, eight were double-positive for ANCA and anti-glomerular basement membrane (anti-GBM). The most common reason for PLEX therapy was severe renal involvement which was present in 87% of patients.
The median follow-up was 41 months at which time 59.6% of the patients were alive and 50% were dialysis-independent. At 3 months, 86% were alive and 66% were dialysis-independent.
The authors reported that the estimated 5-year survival rates were higher in younger patients -- 85% in those under age 50 versus 64.4% in those ages 50-65 and 41% in those over age 65.
The estimated renal survival rates were 65.5% at 1 year and 43% at 5 years. Renal survival was worse in patients older than age 65. There was no difference in renal survival in subgroups with different S-creatinine levels below or above 500 μmol/L, in groups with different antibodies, or between patients with and without alveolar hemorrhage.
However, renal survival was better in patients with higher DEI (above 6) than in those with DEI of 6 or less. "In our experience, higher disease extent index with extra-renal involvement may enable earlier diagnosis and improve renal survival, although this requires further validation," Frausová stated.
The authors noted that there were no deaths or major adverse events directly related to PLEX, although PLEX may lead to removal of coagulation factors and to worsening of alveolar hemorrhage. This may be prevented by substituting fresh frozen plasma at the end of PLEX, they said.
"In our study, infection, and not active vasculitis, was the most common cause of death, which is consistent with previous reports, suggesting that our current treatment strategies are efficacious but may be too aggressive in some patients," they wrote.
As PLEX was routinely used for almost all patients with renal failure, and the vast majority of those with alveolar hemorrhage, the researchers were unable to use a matched control group of patients not treated with PLEX. Another study limitation was that it was retrospective.
According to updated recommendations from the European League Against Rheumatism (EULAR), PLEX can be considered for rapidly progressive glomerulonephritis or severe diffuse alveolar hemorrhage.
Petros Efthimiou, MD, of New York Methodist Hospital in New York City, said the findings don't contribute much to what is already known about the optimal treatment of AAV.
"This was a single center, uncontrolled, retrospective study," noted Efthimiou, who was not involved in the research. "There was a clear selection bias for administration of PLEX to the more severe cases of AAV with renal and pulmonary involvement."
He pointed out that PLEX treatment was an add-on to an immunosuppressive regimen of high dose corticosteroids and cyclophosphamide for induction, followed by oral azathioprine for maintenance.
"There is no data on outcomes when rituximab [Rituxan], which is widely thought of as the new standard of care, is used for induction and/or maintenance," he pointed out.
He agreed that results from the PEXIVAS trial may provide clarity on some of these outstanding issues.
The study was supported by Charles University.
Frausová and co-authors disclosed no relevant relationships with industry.
Efthimiou disclosed no relevant relationships with industry.
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