OP0057\u2005A PERSONALISED RITUXIMAB RETREATMENT APPROACH BASED ON CLINICAL AND B-CELL BIOMARKERS IN ANCA-ASSOCIATED VASCULITIS

Abstract

Time-to-relapse after rituximab for ANCA-associated vasculitis (AAV) is variable and optimal retreatment strategy has been unclear. We previously showed that repopulation of naïve B-cells at 6 months predicts sustained response [1].In AAV following rituximab induction, to evaluate clinical and B-cell predictors of relapse in order to develop a retreatment algorithm.An observational study was conducted in 60 rituximab-treated AAV patients followed for over 10 years. Complete response (CR) was defined as Birmingham Vasculitis Activity Score v3.0 = 0. Retreatment was given on clinical relapse, defined as new features or worsening of persistent disease (not by biomarker status). Peripheral B-cell subsets were measured using highly sensitive flow cytometry. Predictors were tested using multivariable Cox-Regression.Median times-to-retreatment for rituximab cycles 1-5 were 87, 71, 65, 59 and 86 weeks. Over 417 patient-years follow-up, 137 relapses occurred in 50 patients; 16 (in 14 patients) were major (renal=7, neurological=4, ENT=3 and respiratory=2). The major-relapse rate was 3.8/100 patient-years. In multivariable analysis, concomitant immunosuppressant [HR 0.48 (95% CI 0.24–0.94)], achieving CR [0.24 (0.12–0.50)] and naïve B-cell repopulation at 6 months [0.43 (0.22–0.84)] were associated with longer time-to-relapse. Higher baseline memory B-cells [1.01 (1.00–1.02)] were associated with a shorter time-to-relapse. AUROC for prediction of time-to-relapse was greater if guided by naïve B-cell repopulation than if ANCA and/or CD19+ return at 6 months had been used, 0.82 and 0.52 respectively.These data suggest that all patients should receive concomitant oral immunosuppressant. Those with incomplete response or with absent naïve B-cells should be retreated at 6 months. Patients with complete response and naïve repopulation at 6 months should not receive fixed retreatment. This algorithm could reduce hypogammaglobulinaemia due to unnecessary retreatment.Figure 1.A personalised retreatment algorithm for rituximab in ANCA-associated vasculitis[1]Md Yusof et al. Annals of rheumatic diseases (2015) PMID: 25854586.Jack Arnold: None declared, Edward Vital Speakers bureau: Roche, GSK and AstraZeneca, Consultant of: Roche, GSK and AstraZeneca, Grant/research support from: Roche, GSK and AstraZeneca, Shouvik Dass Speakers bureau: Roche and GSK, Aamir Aslam: None declared, Andrew Rawstron: None declared, Sinisa Savic: None declared, Paul Emery Speakers bureau: BMS, Abbott, Pfizer, MSD, Novartis, Roche and UCB, Consultant of: BMS, Abbott, Pfizer, MSD, Novartis, Roche and UCB, Grant/research support from: Abbott, BMS, Pfizer, MSD and Roche., Md Yuzaiful Md Yusof: None declared