Serial ANCA for Wegener

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Motivation: Any time a  patient with Wegener's vasculitis (granulomatosis with polyangiitis) is admitted, the same question pops up on rounds.  Should an ANCA level be sent?  And, how does disease activity change with ANCA?  This question is a controversial one, and even briefly asking around, strong feelings abound about this topic among rheumatologists.  In 2007, one of the largest studies to examine this question was published.

Paper: Finkielman, J.D., Merkel, P.A., Schroeder, D., et. al. "Antiproteinase 3 Antineutrophil Cytoplasmic Antibodies and Disease Activity in Wegener Granulomatosis." Ann. Intern. Med. (2007), 147: 611-619.

Methods: This paper analyzes data from WGET trial, which was a radomized trial evaluating etanercept for maintenance of remission.  Patients who tested positive for antibodies against myeloperoxidase (p-ANCA) were excluded from further analysis both because of small number of patients and because of difference in disease course/phenotype in patients with p-ANCA Wegener's.  In this trial, quantitative measurement of anti-Proteinase 3 (anti-PR3) titers was used.  Serum samples were collected every 3 months.

Results:
Cohort: From the WGET trial, the paper analysed data from 156 patients with median age of 51 and median follow-up of 34 months.  The majority had history of disease activity in ear, nose, and throat (79%), kidneys (54%), and lungs (59%).  At baseline, 85.8% of the cohort had positive ANCA with antibodies against Proteinase 3.  Among the 156 patients, 76 received etanercept while 80 received placebo.

ANCA and Disease Severity: When evaluated across patients in cross-section, there was no statistically significant association between ANCA level titers (anti-PR3) and disease severity (measured by the Birmingham Vasculitis Activity Score), p = 0.07.  When measured longitudinally within the same patients, changes in ANCA levels explained less than 10% for variability in disease activity.

ANCA and Remission/Relapse:  In patients who were positive for ANCA at baseline, after adjusting for age, sex, disease severity, and treatment group, decrease in ANCA levels did not correlate with shorter time to remission (hazard ratio, 1.6 (0.97-2.49)).  Among patients who experienced relapse after remission (54 patients), increase in ANCA levels did not correlate with risk of relapse, adjusted hazard ratio of 1.0 (CI, 0.5-1.9).

Discussion:  Serial ANCA testing is unlikely to be helpful in predicting disease flare/remission or explaining disease activity.  Although ANCA titers taken longitudinally weakly correlated with disease activity, variance in ANCA levels explained less than 10% of disease activity hardly making it the first test to follow for diagnostic or prognostic purposes.  Also, while following patients, if ANCA turns positive, disease activity does not necessarily follow and may not require pre-emptive treatment.  Interestingly, decrease in ANCA was almost statistically significant in predicting shorter time to remission (CI: 0.97-2.49).  While this study may have been underpowered and may be hinting at a significant finding, the association is not strong enough to be visible even with a cohort above 100 patients making it likely a weak correlation.  In summary, while majority of patients with Wegener's have positive PR3 antibody or c-ANCA (about 85% in this group), serial follow-up of ANCA levels after diagnosis is unlikely to be helpful.