medwireNews: The likelihood of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) having a relapse increases if they have anti-proteinase 3 (PR3) ANCA positivity, cardiovascular involvement, or low creatinine levels at diagnosis, shows a meta-analysis.
The investigators found that the risk for relapse was greatest in patients who had both PR3 ANCA positivity and low creatinine levels, leading the team to say that “when presented with patients with both risk factors, [clinicians] must consider a prolonged duration of maintenance therapy.”
However, they caution that “[t]o produce a clinically useful model to stratify risk and guide maintenance treatment duration, we need to identify a greater number of risk factors with a focus towards more robust biomarkers.”
The systematic review included 16 studies – nine randomized controlled trials, five post-hoc analyses, and two cohort studies – investigating risk factors for AAV relapse in a total of 2785 patients.
Of these 16 studies, eight were excluded from the meta-analysis due to single-study risk factors and four due to data duplication, leaving a total of four studies (including one randomized controlled trial) from which three significant risk factors were identified.
In a pooled analysis of the 1041 patients, PR3 ANCA positivity was associated with a significant 69% increased risk for relapse, compared with PR3 ANCA negativity, and cardiovascular system involvement with a significant 78% increased risk.
On the other hand, patients with creatinine levels greater than 200 μmol/L or between 101 μmol/L and 200 μmol/L were a significant 61% and 19% less likely to have a relapse, respectively, than those with levels of 100 μmol/L or below.
The association between worse renal function and reduced risk for relapse is “arguably contradictory to what we may expect,” say the researchers, who postulate that “this may be due to the immune dysfunction caused by renal failure.”
The results of the meta-analysis were supported in a validation cohort of 182 patients at a single tertiary center, 41% of whom had a relapse within 5 years of follow-up. In Cox regression analysis, patients with PR3 ANCA positivity and low creatinine levels had the greatest risk for relapse, with a relapse-free survival rate of approximately 30% at 60 months versus 60–80% among patients with other PR3 ANCA and creatinine profiles.
Notably, cardiovascular system involvement had to be excluded from this analysis due to a low incidence rate (6%) in the cohort.
The researchers developed a prognostic model based on the three risk factors and it predicted relapse within 5 years with 62% accuracy when tested in the validation cohort.
“This model we created appeared to be a modest approximation of relapse risk, but we could not reliably test cardiovascular involvement within the model as its incidence is rare,” explain Catherine King (University of Birmingham, UK) and co-investigators in Rheumatology Advances in Practice.
They conclude: “There should be scope for post-hoc analysis of more recent trials such as RITUXVAS to recognise new factors and endorse already identified factors affecting outcome in AAV.
“A greater focus on biomarkers may provide more robust risk factors.”
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