English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background/Aims  Time-to-relapse after rituximab for ANCA vasculitis is variable and optimal retreatment strategy is unclear. We previously showed that repopulation of naïve B-cells at 6 months predicts sustained response. Our objective was to evaluate clinical and B-cell predictors for relapse in multivariable analysis to develop a retreatment algorithm. Methods  An observational study was conducted in 60 rituximab-treated AAV patients over 10-years. Complete response was defined as a Birmingham Vasculitis Activity Score (BVAS) v3.0=0. Repeat rituximab cycles were given on clinical relapse. Naïve, memory B-cells and plasmablasts were measured using highly sensitive flow cytometry. Clinical and B cell predictors were analysed in multivariable analysis (MVA) to develop a retreatment algorithm. Results  Patients were: 33/60 (55%) male, mean(SD) age 51(19), 39/60 (65%) received concomitant immunosuppressants and 54/60 (90%) had prior therapy with cyclophosphamide. Median times to retreatment for 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 lungs=2). The major-relapse rate was 3.8/100 patient-years. Results of MVA are shown in the table. With naïve B-cell repopulation at 6 months, relapse rates at 12 and 18 months were 5% and 16%, versus 45% and 59% without naïve repopulation (p &amp;lt; 0.001). Relapse rates at 18 and 24 months were 17% and 54% with naïve repopulation at 12 months versus and 29% and 71% without (p = 0.045). AUROC for time-to-relapse was greater if retreatment was guided by naïve B-cell repopulation than if ANCA and/or CD19+ return was used at 6 months, 0.82 and 0.52 respectively. Conclusion  These results suggest the following: (i) all patients should receive an oral immunosuppressant; (ii) patients with incomplete remission should be retreated at 6 months; (iii) patients with complete remission but absent naïve B cells at 6 months should be retreated at 6 months; (iv) patients with complete remission and naïve B-cell return may not be appropriate for fixed retreatment. For this last group monitoring of clinical symptoms and B-cells may be effective and future work will address this further. This algorithm could avoid hypogammaglobulinaemia due to unnecessary retreatment. P207 Table 1:Factors associated with time-to-relapse to first cycle rituximabRisk FactorsUnivariable analysisHR (95% CI); p-values(with multiple imputation)Multivariable analysis (MVA)HR (95% CI); p-values(with multiple imputation)Age, per 10 years (BL)1.01 (0.86 – 1.17); p = 0.954Not included in MVAFemale (BL)1.15 (0.65 – 2.02); p = 0.629Not included in MVADisease duration, years (BL)1.06 (0.98 – 1.15); p = 0.160Included in MVA but removed from final model as p &amp;lt; 0.20Concomitant immunosuppressant (BL)0.69 (0.39 – 1.22); p = 0.2050.48 (0.24 – 0.94); p = 0.034Positive ANCA immunofluorescence (BL)0.89 (0.46 – 1.71); p = 0.725Not included in MVAPositive anti-PR3/anti-MPO (BL)0.57 (0.31 – 1.06); p = 0.077Included in MVA but removed from final model as p &amp;lt; 0.20CRP, mg/L (BL)1.00 (0.99 – 1.01); p = 0.456Not included in MVABVAS 3.0 per point score (BL)0.99 (0.94 – 1.05); p = 0.763Included in MVA but removed from final model as p &amp;lt; 0.20VDI per point score (BL)1.14 (0.87 – 1.50); p = 0.353Not included in MVANaïve B-cells, x 10 9/L* (BL)1.00 (1.00 – 1.01); p = 0.797Not included in MVAMemory B-cells, x 10 9/L* (BL)1.01 (1.00 – 1.02); p = 0.0401.01 (1.00 – 1.02); p = 0.045Plasmablasts, x 10 9/L* (BL)1.04 (0.94 – 1.16); p = 0.459Not included in MVAComplete depletion at 6 Weeks post-RTX0.90 (0.50 – 1.61); p = 0.721Not included in MVAComplete Response (26Wk)0.34 (0.19 – 0.61); p &amp;lt; 0.0010.24 (0.12 – 0.50); p &amp;lt; 0.001Positive ANCA immunofluorescence (26Wk)0.99 (0.56 – 1.75); p = 0.962Not included in MVAPositive anti-PR3/anti-MPO (26Wk)0.79 (0.44 – 1.42); p = 0.426Not included in MVACRP, mg/L (26Wk)0.99 (0.97 – 1.02); p = 0.618Not included in MVANaïve B-cell repopulation (26Wk)0.38 (0.19 – 0.76); p = 0.0060.43 (0.22 – 0.84); p = 0.013Memory B-cell repopulation (26Wk)0.45 (0.20 – 0.99); p = 0.046Included in MVA but removed from final model as p &amp;lt; 0.20Plasmablast cell repopulation (26Wk)1.14 (0.61 – 2.13); p = 0.675Not included in MVABL = baseline, 26Wk = 26 weeks. Disclosure  J.E. Arnold: None. E.M.J. Vital: Honoraria; Roche, GSK, AstraZeneca. S. Dass: Honoraria; Roche, GSK. A. Aslam: None. A.C. Rawstron: None. S. Savic: Honoraria; Novartis, Swedish Orphan Biovitrum, Sire. Grants/research support; Novartis, Swedish Orphan Biovitrum, Octapharma, CSL Behring. P. Emery: Consultancies; BMS, Abbott, Pfizer, MSD, Novartis, Roche, UCB. Grants/research support; Abbott, BMS, Pfizer, MSD, Roche. M. Md Yusof: None.

rheumatology

P207 A proposal for individually tailored rituximab treatment based on clinical and B-cell biomarkers for remission maintenance in ANCA associated vasculitis