Thursday, February 28, 2019

ANCA titers and Disease flare.

Does a rise in ANCA titers predict a disease flare? — This has been a controversial area in the literature almost since ANCA were first identified in the 1980s. However, several rigorous studies have demonstrated that elevations in the titers of ANCA do not predict disease flares in a timely manner . The largest of these studies was performed on a clinical trial cohort of 180 patients (Wegener's Granulomatosis Etanercept Trial [WGET] Research Group, 2005), with serum samples drawn at three-month intervals and ANCA assays performed at the Mayo Clinic . The following findings were observed:
●Among patients who were PR3-ANCA positive compared with negative at baseline, there were no differences in the median time to relapse, disease activity score , or organ involved at relapse. Decreases in PR3-ANCA levels were not associated with a shorter time to remission, and increases were not associated with relapse.
●Relapses occurred among 46 of 101 patients (46 percent) who were mature-PR3-ANCA positive at baseline and achieved remissions of at least six months' duration. However, the proportion of patients who experienced a disease flare within one year of an elevation in ANCA titer was only 40 percent.
Other studies have come to slightly different conclusions, indicating that persistently high or rising titers of ANCA are associated with an increased risk of disease relapse . However, even in those studies, the temporal relationship between a rise in ANCA titer and the occurrence of a disease flare was poor. As an example, in a prospective study of 100 ANCA-positive patients observed over a two-year period, relapse did not occur in 43 and 29 percent of those with a rise in ANCA titers by immunofluorescence and in PR3-ANCA titers by ELISA, respectively .
In addition, a meta-analysis of 18 studies found that neither a rise in ANCA titer nor a persistently elevated ANCA titer were strong predictors of a subsequent disease flare . Therapies for relapsed ANCA-associated vasculitis (often, high doses of glucocorticoids and cytotoxic agents) carry substantial risk, including severe infections, cystitis, bladder cancer, lung fibrosis (rarely), and death. Treating all patients with increases in ANCA titers would result in unnecessary risks of toxicity in a substantial percentage of patients, nearly 30 percent in the study mentioned above. Because of these concerns, using a rise in ANCA titer as the sole parameter to justify altering immunosuppressive therapy cannot be endorsed.
A reasonable recommendation is to closely follow patients with rising ANCA titers but not to alter their therapy unless there are clear clinical signs of active disease.

Bhopalwala. H

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