BACKGROUND: For treating ANCA-associated vasculitis in last few years, newer immunosuppressive regimens (Rituximab + steroid) are coming up with the aim of reducing cumulative dose and side effects of immunosuppression (EUVAS) while having same efficacy as induction agents.
AIM OF THE STUDY: 1. To describe the clinical spectrum of the disease and 2. describe the efficacy and safety of cyclophosphamide and Rituximab as induction agents. Methods: A single-center observational retrospective study consisting of 33 indoor patients of Nephrology department I.P.G.M.E & R SSKM HOSPITAL KOLKATA in between JAN 2021- MARCH 2022 with 6 months of follow-up. ANCA MPO PR3 were estimated by IIF and ELISA. Induction therapy was given according to institutional protocol (EUVAS / RAVE).
RESULTS: Total 33 patients were included; new cases were 90.9% (30) and 9.1% (3) were relapse cases, 10 were male (30.3%), 23 were female (69.9%). Mean age was (39.6 yrs  ± 16.9 yrs). 16 (48.48%) were MPO +, 10 (30.3%) were PR3, 1 (3.03%) was positive for both, 6 (18.18%) were ANCA- ANTI-GBM overlap. RPRF presentation was in 20 cases (60.6%), HD requiring at presentation 18 (54.54%), DAH in 12 patients (36.36%), other systemic symptoms were mostly joint pain, skin rash, fever, weight loss. Mean baseline creatinine —(5.6 ± 2.57) mg/dl, mean baseline 24 hours proteinuria — (1.5  ± 0.89 gms/day). 17 patients (51.51%) were given Plasmapheresis, however for 4 patients, it had to be discontinued after 2-3 sessions due to coagulopathy, severe thrombocytopenia, sepsis. Indications for plasmapheresis were DAH (70.58%), ANCA- ANTI GBM OVERLAP (29.4%), HD requiring at presentation (100%). For 2 (6.06%) patients, PLEX could not be initiated due to hemodynamic instability, severe anaemia, and thrombocytopenia. EUVAS protocol was used for induction therapy in 21 new patients (70%); RAVE protocol was used for induction therapy in 7 new patients (23.3%). For relapse cases, 1 (33.3%) patient was treated with EUVAS protocol, 2 patients (66.67%) were treated with RAVE protocol. For 2 new cases (6.67%), no induction therapy could be started because of severe sepsis at presentation. 13 (59.09%) had infections in EUVAS arm : 8 had LRTI (61.5%), 5 had G.I sepsis (38.46%), 4 had septic shock (30.76%). 11 (50%) had bone marrow suppression in EUVAS arm. 1 (11.1%) had symptomatic UTI in RAVE arm. EUVAS had to discontinued in 4 new patients (19.04%) due to severe sepsis, bone marrow suppression, and progression to CKD-5D. There was no discontinuation in RAVE arm. Total 7 deaths were recorded; out of 7, 3 had MPO vasculitis, 3 had PR3 vasculitis, 1 had ANCA-ANTI-GBM overlap. 3 patients died within 1 month of diagnosis (42.86%), 1 patient (14.29%) died within 1-3 months, 3 patients (42.86%) died after 3 months of diagnosis. Deaths within 1st 3 months were due to pneumonia, sepsis, DAH, coagulopathy. Deaths after 3 months were due to cardiac arrhythmia (1), infective endocarditis (1), and acute left ventricular failure (1). All of them were in EUVAS arm, none died in RAVE arm. In the EUVAS arm (22), 9 (40.9%) had complete remission (proteinuria : <500 mg/day, creatinine <1 mg/dl) at the end of 6 doses; 2 (9.09%) had partial remission (proteinuria reduction >50% from baseline, creatinine 50% reduction from baseline), 4 (18.18%) had early discontinuation and developed CKD-5D, 2 patients had complete course (1.64%) but progressed to CKD-5D. In the RAVE arm (9), 8 (88.89%) had creatinine <1 mg/dl within 3 months of completing induction, 100% had proteinuria of <500 mg/day. After 3 months of initial presentation, 6 (20.68%) had developed CKD-5D [(MPO+ 2),(PR3 +2),(ANCA- ANTI-GBM overlap 2)]. Rest all were HD free at the end of 3 months. Total 33 patients were included; new cases were 90.9% (30) and 9.1% (3) were relapse cases, 10 were male (30.3%), 23 were female (69.9%). Mean age was (39.6 yrs  ± 16.9 yrs). 16 (48.48%) were MPO +, 10 (30.3%) were PR3, 1 (3.03%) was positive for both, 6 (18.18%) were ANCA- ANTI-GBM overlap. RPRF presentation was in 20 cases (60.6%), HD requiring at presentation 18 (54.54%), DAH in 12 patients (36.36%), other systemic symptoms were mostly joint pain, skin rash, fever, weight loss. Mean baseline creatinine —(5.6 ± 2.57) mg/dl, mean baseline 24 hours proteinuria — (1.5  ± 0.89 gms/day). 17 patients (51.51%) were given Plasmapheresis; however, for 4 patients, it had to be discontinued after 2-3 sessions due to coagulopathy, severe thrombocytopenia, sepsis. Indications for plasmapheresis were DAH (70.58%), ANCA- ANTI GBM OVERLAP (29.4%), HD requiring at presentation (100%). For 2 (6.06%) patients, PLEX could not be initiated due to hemodynamic instability, severe anaemia, and thrombocytopenia. EUVAS protocol was used for induction therapy in 21 new patients (70%), RAVE protocol was used for induction therapy in 7 new patients (23.3%). For relapse cases, 1 (33.3%) patient was treated with EUVAS protocol, 2 patients (66.67%) were treated with RAVE protocol. For 2 new cases (6.67%), no induction therapy could be started because of severe sepsis at presentation. 13 (59.09%) had infections in EUVAS arm : 8 had LRTI (61.5%), 5 had G.I sepsis (38.46%), 4 had septic shock (30.76%). 11 (50%) had bone marrow suppression in EUVAS arm. 1 (11.1%) had symptomatic UTI in RAVE arm. EUVAS had to discontinued in 4 new patients (19.04%) due to severe sepsis, bone marrow suppression, and progression to CKD-5D. There was no discontinuation in RAVE arm. Total 7 deaths were recorded; out of 7, 3 had MPO vasculitis, 3 had PR3 vasculitis, 1 had ANCA-ANTI-GBM overlap. 3 patients died within 1 month of diagnosis (42.86%), 1 patient (14.29%) died within 1-3 months, 3 patients (42.86%) died after 3months of diagnosis. Deaths within 1st 3 months were due to pneumonia, sepsis, DAH, coagulopathy. Deaths after 3 months were due to cardiac arrhythmia (1), infective endocarditis (1), and acute left ventricular failure (1). All of them were in EUVAS arm, none died in RAVE arm. In the EUVAS arm (22), 9 (40.9%) had complete remission (proteinuria : <500 mg/day, creatinine <1 mg/dl) at the end of 6 doses; 2 (9.09%) had partial remission (proteinuria reduction >50% from baseline, creatinine 50% reduction from baseline), 4 (18.18%) had early discontinuation and developed CKD-5D, 2 patients had complete course (1.64%) but progressed to CKD-5D. In the RAVE arm (9), 8 (88.89%) had creatinine <1 mg/dl within 3 months of completing induction, 100% had proteinuria of <500 mg/day. After 3 months of initial presentation, 6 (20.68%) had developed CKD-5D [(MPO+ 2),(PR3 +2),(ANCA- ANTI-GBM overlap 2)]. Rest all were HD free at the end of 3 months.
CONCLUSIONS: In our study, EUVAS cohort had more evidences of infections and mortality. Based on this data, future RCTs are needed to avoid selection bias and for acquiring better comparative data.