Abstract
BackgroundTime to relapse after rituximab for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is variable, and optimal retreatment strategy has remained unclear. In AAV following rituximab induction, the study objective was to evaluate clinical and B-cell predictors of relapse in order to develop a retreatment algorithm.MethodsA retrospective observational study was conducted in 70 rituximab-treated ANCA-associated vasculitis patients followed up 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.ResultsMedian time to retreatment for cycles 1–5 were 84, 73, 67, 60, and 73 weeks. Over 467 patient-years follow-up, 158 relapses occurred in 60 patients; 16 (in 15 patients) were major (renal = 7, neurological = 4, ENT = 3, and respiratory = 2). The major-relapse rate was 3.4/100 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. Personalized retreatment using these three predictors in this cohort would have avoided an unnecessary fixed retreatment in 24% of patients. Area under the receiver operating characteristic for prediction of time to relapse was greater if guided by naïve B-cell repopulation than if previously evaluated ANCA and/or CD19+ cells return at 6 months had been used, 0.82 and 0.53, respectively.ConclusionOur findings suggest that all patients should be coprescribed 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 should not receive fixed retreatment. This algorithm could reduce unnecessary retreatment and warrant investigation in clinical trials.
Highlights
Rituximab, a chimeric anti-CD20 monoclonal antibody is licensed for remission induction of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)
Concomitant immunosuppressant [HR, 0.48], achieving Complete response (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
Area under the receiver operating characteristic for prediction of time to relapse was greater if guided by naïve B-cell repopulation than if previously evaluated ANCA and/or CD19+ cells return at 6 months had been used, 0.82 and 0.53, respectively
Summary
A chimeric anti-CD20 monoclonal antibody is licensed for remission induction of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). (i) Fixed retreatment, which may vary internationally either using 500 mg × 2 infusions followed by 500 mg infusion every 6 months or 1,000 mg infusion every 4 months or 1,000 mg infusion every 6 months for 18 months [7, 8], with this regimen extended to 5 years in patients at higher risk of relapse [9] This is associated with low rates of relapse but may lead to hypogammaglobulinemia and serious infection; an effect that we showed was exacerbated if cyclophosphamide had been previously used and which predicted severe infection [2, 10,11,12,13]. In AAV following rituximab induction, the study objective was to evaluate clinical and B-cell predictors of relapse in order to develop a retreatment algorithm
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
