Plasma Exchange Shows Little Benefit in AAV Treatment, Meta-analysis Finds

Adding plasma exchange to immune-suppressing treatment does not significantly improve clinical outcomes in people with ANCA-associated vasculitis (AAV), a new meta-analysis indicates.

The analysis, “The role of plasma exchange in antineutrophil cytoplasmic antibody-associated vasculitis: a meta-analysis,” was published in Clinical Rheumatology.

AAV is characterized by inflammation in the blood vessels, often driven by antibodies (ANCAs) that target certain cells of the immune system and cause them to go haywire. Standard AAV treatment involves medications that reduce the activity of the immune system, thereby reducing inflammation.

Plasma exchange involves removing and replacing a person’s plasma, the liquid portion of blood that contains water, salts and enzymes. This can remove certain disease-causing proteins, such as ANCAs, but the usefulness of plasma exchange as a possible treatment for AAV remains controversial.

Researchers at the National and Kapodistrian University of Athens, in Greece, conducted a meta-analysis of published studies to clarify the safety and effectiveness of plasma exchange in AAV patients.

In a meta-analysis, data from multiple previously-published studies is combined and analyzed collectively. This allows for a more holistic assessment than any single study.

“The aim of the present meta-analysis is to evaluate the effect of PLEX [plasma exchange] on patients with AVV and clarify its influence on mortality, ESRD [end-stage kidney disease], relapses, and severe adverse events,” the researchers wrote.

The researchers identified 10 relevant studies, including both clinical trials and retrospective studies. In total, these included data on 1,235 AAV patients, of whom 633 received conventional immunosuppressive treatment and 602 were treated with plasma exchange in addition to standard therapy.

Using statistical models, the researchers evaluated whether the addition of plasma exchange was associated with better treatment outcomes.

There were no significant differences in mortality rates with or without plasma exchange at three months or at one year. Similarly, there were no differences in rates of end-stage kidney disease, or loss of kidney function, at these time points. There also were no significant differences in terms of disease relapses, infections, or rates of adverse events (side effects).

The researchers also performed time-to-event analyses. This is a type of statistical analysis that assesses how long it takes to reach a certain well-defined endpoint — in this case, the researchers assessed both mortality and end-stage kidney disease. While plasma exchange was not associated with an altered mortality risk, it significantly decreased the risk of end-stage kidney disease (by 29%).

“The findings of the present meta-analysis indicate that the use of PLEX does not influence short-term outcome,” the researchers concluded. “Specifically, both mortality and ESRD rates within the first year after diagnosis were similar in both groups.”

The researchers then conducted “leave-one-out” analyses to verify these results. As the name suggests, this type of analysis involves repeating the same analyses, but leaving out the result of different individual studies. This can help ensure the results are not being too strongly affected by one single study, which could be an outlier (for reasons ranging from problems in the study design to simple random chance).

While the leave-one-out analyses didn’t reveal differences concerning mortality, the effect of plasma exchange on end-stage kidney disease was not significant when one of the studies — results from the MEPEX Phase 2/3 clinical trial (NCT01408836) — was excluded.

“Although our analysis showed significantly decreased overall incidence of ESRD, this result was mainly driven by the MEPEX trial. In addition, the MEPEX trail per se did not show any positive effect of PLEX on long-term outcome, including mortality and ESRD,” the researchers wrote. “Thus, this clinical question may warrant further exploration.”

They noted that future studies to explore whether certain patients are most likely to benefit from plasma exchange, in terms of kidney disease, may be warranted.

In the meantime, “the findings of the present meta-analysis do not support the wide use of PLEX for the management of AAV, since it did not lead to decreased overall mortality rates,” the researchers concluded.