Background Following remission induction with rituximab (RTX) in ANCA-associated vasculitis (AAV), duration of response is highly variable [1,2]. Repeat cycles may be fixed-interval or on clinical relapse. The former may lead to hypogammaglobulinaemia and severe infection leading to discontinuation in up to 1/3 patients . However, the latter may allow severe flares. Hence biomarkers that can guide best time to retreat are needed.
Objectives To investigate whether B cell biomarkers may have value in guiding retreatment decisions in patients with response to RTX.
Methods We conducted an observational study of patients with AAV treated after a cycle of RTX in a single centre between January 2006 and September 2013 – a total of 162 patient-years follow up. Each cycle consisted of 2×1000mg infusions repeated on clinical relapse. B cells were measured using highly sensitive flow cytometry (HSFC) as previously described  at baseline, week 2, week 6 and week 26 after RTX. 12 healthy controls were used to measure normal B cell subsets and 26-week B cell subsets were compared to our previously published data in RTX-treated RA and SLE.
Results 35 patients (18 female, median age 56) received a first cycle (C1). ANCA positivity were PR3: 25, MPO: 5 and immunofluorescence only: 4. 34 (97%) patients were resistant to conventional immunosuppressants, including relapse or non-response after cyclophosphamide in 31 (89%). 22 (63%) continued oral immunosuppressants.
Prior to RTX, active AAV was characterised by naïve- and memory-B lymphopenia compared to healthy controls at baseline. This dysregulation was more marked in patients with raised CRP. Overall response rate to C1 was 94%. Median time to relapse was 81 weeks (range 31-209). Naïve, memory and plasmablast numbers at 26 weeks were significantly lower in AAV compared to RA or SLE (all p<0.05).
We found a significant association between repopulation of naïve B cells at 6 months and later clinical relapse (more than 18 months); (p=0.010) as shown in Figure 1. No association between memory B cell (p=0.399) or plasmablast repopulation (p=0.262) and relapse (in contrast to our finding in SLE ). Patients with undetectable (<0.0001×109 cells/L) naïve B cells at 6 months had lower naïve B cells and significantly higher CRP (p=0.015) at baseline, but no difference in age, disease duration, Birmingham Vasculitis Activity Score (BVAS) or ANCA titres. Of patients with detectable naïve B cells, 100% did not experience a relapse within the next 26 weeks and 83% within the next 52 weeks. The same trend followed subsequent cycles; for cycle 2 and 3 (n=12 and n=8 respectively, 100% did not relapse in the following 26 weeks).
Conclusions Naïve B-lymphopenia is a B cell specific marker of disease activity in AAV. Evaluation of naïve B cell numbers in very early repopulation using HSFC may have value in guiding retreatment decisions and warrants validation in larger cohorts.
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Disclosure of Interest None declared
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