Naive lymphopenia may be a B cell–specific marker of disease activity in ANCA-associated vasculitis that could help guide when to retreat patients with B cell depletion–therapy, researchers report.

In a study of 35 patients with severe ANCA associated vasculitis (AAV) who were treated with B cell depletion therapy with rituximab, relapse was more likely in those patients who did not experience naive B cell repopulation at 6 months, the researchers reported in the Annals of the Rheumatic Diseases (Annals Rhem Dis 2015; [doi: 10.1136/annrheumdis-2014-206496]).

A single cycle of B cell depletion with rituximab has been effective for inducing remission in patients with AAV, but an optimal long-term strategy had not yet been established. In rheumatoid arthritis, repeat cycles were often given when patients developed clinical relapse, but this approach may be riskier in AAV since relapses may cause life or organ threatening disease, according to Dr. Paul Emery of the Leeds Institute of Rheumatic and Musculoskeletal Diseases and his associates.

“An alternative approach is to use pre-emptive treatment either based on reconstitution of B cells or fixed intervals,” they wrote. However the identification of biomarkers that could guide these decisions would be very valuable, they said.

The study of 35 patients with AAV received treatment with two infusions of rituximab at a dose of 1,000 mg , that was repeated 2 weeks later; the treatment was then repeated in patients with clinical relapse for up to five cycles. Disease activity was assessed at baseline and every 3 months using the Birmingham Vasculitis Activity Score (BVAS). Peripheral B cell subsets were measured using highly sensitive flow cytometry (HSFC) at week 0, 6, and 26 without knowledge of clinical status other than time since rituximab.

Complete response was defined as a BVAS score of zero, and partial response was defined as 50% improvement in BVAS from baseline at week 26. Response rates for cycle 1 to cycle 5 were 94%, 100%, 85%, 85%, and 83%, respectively, the study authors reported. Patients with early relapse failed to develop naive B cells, a finding that differed from results seen in SLE, the authors noted.

However, repopulation of naive B cell at 6 months was associated with a reduced risk of relapse (hazard ratio, 0.326; 95% confidence interval, 0.114-0.930, P=0.036). Relapse rates at 12 and 18 months were 0% and 14% with naive repopulation at 6 months, and 31% and 54% without naive repopulation. “Patients with undetectable naive B cells at 6 months may be suited for earlier retreatment due to 30% relapse rate observed at 12 months,” they said.

The results suggest that evaluation of naive B cell numbers in very early repopulation using HSFC may have value in guiding retreatment decisions for the most effective and efficient use of rituximab in AAV, the study authors concluded. The results warranted validation in larger cohorts, they added.


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