AB0561 B cell therapy in refractory/ relapsed anca associated vasculitis- a single centre prospective observational study

Abstract

BackgroundRituximab (Rtx), a novel biological, having B cell depletion mechanism is an anti- CD 20 antibody and is found to be useful in patients of ANCA associated vasculitis. In AAV the disease activity correlates with increased circulating B cells. Rituximab has been found to be useful in depleting these B cells. According to the RAVE study, Rituximab was shown to be non-inferior to Cyclophosphamide in inducing remission. It also showed that the regimen (Rtx) may be superior to the standard regimen of Cyclophosphamide and glucocorticoids for remission induction in severe relapsing ANCA-associated vasculitis.In our study, B cell therapy was given in those patients only who had persistent disease activity or relapse.ObjectivesTo assess response of Rtx in relapsed /refractory cases of AAV and show that it is a good therapeutic stratergy in such cases.MethodsIn our cohort there were 49 patients of ANCA associated vasculitis, diagnosed by clinical and serological criteria, (by both ELISA and IFA) classified according to ACR criteria and supported, wherever possible, by biopsy. In this prospective study, patients were seen during January 2012 to January 2017. A total of 15 patients received Rituximab for various reasons. Rituximab (Rtx) was given as 1 gram infusion on day 1 and day 15 as induction therapy and subsequently 6 monthly maintenance doses of 500 mg were administered. No other immunosuppression other than steroids were given.ResultsMedian follow up was 22 months. All patients had recieved Cyclophosphamide (median dose 6 grams) and 1mg/kg glucorticoids at onset. Among the patients who received Rituximab, all had anti PR3 antibody positive & all were GPA clinically. 14 patients (93.33%) had lung involvement, renal involvement was seen in 7 (46.6%) patients, 13 (86.6%) patients had upper respiratory tract involvement, 6 (40%) had ophthalmic involvement. Nervous system involvement was seen in 5 (33.3%) and myocarditis was seen in 3 (20%) each. 3 (20%) patients had gangrene.Indications for receiving Rtx were heterogenous. It was given for involvement of lung, renal, ophthalmic, upper respiratory and nervous system in 6 (40%), 3 (20%), 3 (20%), 1 (6.66%) and 1 (6.66%) respectively. Whereas 1 (6.66%) patient received Rtx for persistent disease activity.12 out of 15 patients (80%) achieved remission at mean follow up of 3 months while one achieved at 6 months follow up & all maintained continued remission. 1 patient was due for 3-month follow up. 1 patient died due to lung infection during the course. 4 patients had permanent morbidities/organ damage which they already had before starting Rtx. Only one patient had infusion reaction at the end of 1st induction however she remained in remission after the first dose itself.Conclusions86.6% patients achieved remission after Rtx and remained in continous remission at median follow up of 22 months. Rtx is a very good therapeutic strategy for refractory/relapsed especially PR3+ AAV also it can be used as a maintenance regimen for long term.References Stone JH, Merkel PA, ...