A Personalized Rituximab Retreatment Approach Based on Clinical and B-Cell Biomarkers in ANCA-Associated Vasculitis

Background: Time 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. Methods: A 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. Results: Median 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 naive 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 naive 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. Conclusion: Our findings suggest that all patients should be coprescribed oral immunosuppressant. Those with incomplete response or with absent naive B cells should be retreated at 6 months. Patients with complete response and naive repopulation should not receive fixed retreatment. This algorithm could reduce unnecessary retreatment and warrant investigation in clinical trials.

Automated summary

The study found that the time to relapse after rituximab treatment for ANCA-associated vasculitis varies, and a personalized retreatment strategy can reduce unnecessary retreatments. Factors associated with longer relapse time include concomitant immunosuppressant use, achieving complete response, and naive B-cell repopulation at 6 months.