Treating Patients with ANCA-Associated Vasculitis and Very Severe Renal Injury with an Intensified B Cell Depletion Therapy: Comparison with a Control Cohort Receiving a Conventional Therapy

Dario Roccatello¹, Savino Sciascia², SILVIA GRAZIETTA FODDAI³, gIACOMO QUATTROCCHIO⁴, MASSIMO RADIN³, IRENE CECCHI³, ALICE BARINOTTI³, ELENA RUBINI³, MICHELA FERRO⁴, EMANUELE DE SIMONE⁴, carla naretto⁴, ANTONELLA BARRECA⁵, ANDREA SAMMARTINO⁴, DANIELA ROSSI⁴ and ROBERTA FENOGLIO⁴, ¹University of Torino, Torino, Italy, ²University of Turin, Torino, Italy, ³University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy, ⁴University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hub Hospital, Turin, Italy, ⁵Pathology Unit, Città della Salute e della Scienza, Turin, Italy

Meeting: ACR Convergence 2023

Keywords: ANCA associated vasculitis, Granulomatosis with Polyangiitis (GPA), Nephritis, Vasculitis

Session Information

Date: Sunday, November 12, 2023

Title: (0673–0690) Vasculitis – ANCA-Associated Poster I: Treatment Outcomes

Session Type: Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Rituximab (RTX), an anti-CD20 monoclonal antibody, has shown to be an effective induction treatment for small-vessel vasculitides associated with antineutrophil cytoplasm antibodies (AAV) in both newly diagnosed and relapsing patients. However, the role of RTX in the management of the most severe cases of AAV remains to be fully elucidated. Objective of the study

to assess both safety and efficacy of an intensified B-cell depletion therapy (IBCDT) protocol, including RTX, cyclophosphamide (CYC), and methylprednisolone pulses without additional maintenance immunosuppressive therapy compared to conventional therapy regimen based on oral CYC and steroids and prolonged maintenance therapy with azathioprine (AZA) in patients with AAV and severe renal injury.

Methods: A cohort of 15 AAV patients with the most severe features of AVV renal involvement (as < 15 ml/min GFR and histological findings of paucimmune necrotizing glomerulonephritis with more than 50% crescents of non-sclerotic glomeruli at the renal biopsy) was treated IBCDT and compared to compared toa control group of 10 patients with AAV treated with a conventional therapy regimen based on oral CYC and steroids and prolonged maintenance therapy with azathioprine (AZA). Independently on the pharmacologic regimen, plasma exchange (7 procedures with 1-1.5 plasma volume replacement) was performed in the presence of 1. alveolar haemorrhage, and 2.more than 50% florid crescents in the nonsclerotic glomeruli, or 3. dialysis dependence.

Results: Complete clinical remission (BVAS 0) was observed at 6 months in 14 of 15 patients (93%). All cases treated with IBCDT who achieved a complete clinical remission experienced a depletion of peripheral blood B cells at the end of therapy. Of the 10 dialysis dependent patients at onset, 6 subjects (60%) experienced a functional recovery allowing the suspension of dialysis treatment. When compared to the control group, no statistically significant difference was observed in patients treated with IBCDT in terms of overall survival, 6-month therapeutic response rate, and 6-, and 12-month functional renal recovery. The cumulative total dose of CYC in the case group was on average 1 g/patient while in the control group on average 8.5 g / patient (p = 0.00008). Plasmapheresis sessions were performed at part of the induction therapy among 13 patients (87%) in the case group and 8 (80%) in the control group.

Conclusion: The results of this study showed that IBCDT appeared to be safe and has the same efficacy profile when compared to conventional therapy with CYC plus AZA in the management of the most severe patients with AAV. Additionally, this avoids the need of prolonged maintenance therapy for long, and limits the exposure to CYC with consequent reduced toxicity and drug-related side effect rates.

Disclosures: D. Roccatello: None; S. Sciascia: None; S. FODDAI: None; g. QUATTROCCHIO: None; M. RADIN: None; I. CECCHI: None; A. BARINOTTI: None; E. RUBINI: None; M. FERRO: None; E. DE SIMONE: None; c. naretto: None; A. BARRECA: None; A. SAMMARTINO: None; D. ROSSI: None; R. FENOGLIO: None.

To cite this abstract in AMA style:

Roccatello D, Sciascia S, FODDAI S, QUATTROCCHIO g, RADIN M, CECCHI I, BARINOTTI A, RUBINI E, FERRO M, DE SIMONE E, naretto c, BARRECA A, SAMMARTINO A, ROSSI D, FENOGLIO R. Treating Patients with ANCA-Associated Vasculitis and Very Severe Renal Injury with an Intensified B Cell Depletion Therapy: Comparison with a Control Cohort Receiving a Conventional Therapy [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/treating-patients-with-anca-associated-vasculitis-and-very-severe-renal-injury-with-an-intensified-b-cell-depletion-therapy-comparison-with-a-control-cohort-receiving-a-conventional-therapy/. Accessed .

« Back to ACR Convergence 2023

ACR Meeting Abstracts - https://acrabstracts.org/abstract/treating-patients-with-anca-associated-vasculitis-and-very-severe-renal-injury-with-an-intensified-b-cell-depletion-therapy-comparison-with-a-control-cohort-receiving-a-conventional-therapy/