POS0704 LONG-TERM CLINICAL OUTCOMES OF PATIENTS WITH LUPUS NEPHRITIS TREATED WITH AN INTENSIFIED B-CELL DEPLETION PROTOCOL: A PROSPECTIVE STUDY

Background:B cells play a key role In the pathogenesis of Lupus Nephritis (LN).Objectives:we aim to investigate the safety and efficacy of an intensified B-cell depletion induction therapy (IBCDT)without immunosuppressive maintenance regimen compared to standard of care in biopsy-proven LN.Methods:Thirty patients were administered an IBCDT (4 weekly Rituximab 375mg/m2 and 2more doses after 1&2 months;2 infusions of 10 mg/kg cyclophosphamide (CYC),3 methylprednisolone pulses), followed by oral prednisone (tapered to 5 mg/day by the 3rd month). No immunosuppressive maintenance therapy was given. Thirty patients matched for LN class and age were selected as controls: 20 received 3 methylprednisolone pulses days followed by oral prednisone and mycophenolate mofetil (MMF) 2-3 g/day, while 10 were given the Euro Lupus CYC.Results:At 12 months, complete renal remission was observed in 93% of patients on IBCDT, in 62.7% on MMF, and in 75% on CYC (p=0,03); the dose of oral prednisone was lower in the IBCDT group (mean±SD 2.9±5.0mg/dl) than MMF (10.5±8.0 mg/day,p<0.01) or CYC group (7.5±9.0mg/day,p<0.01). Mean follow-up after treatment was 44.5 months (IQR 36–120months), 48.6 months (IQR36–120months), and 45.3 (IQR36–120months) for IBCDT, MMF and CYC, respectively. At their last follow-up visit, we observed no significant differences in proteinuria and serum creatinine, nor in the frequency of new flares among the three groups.Conclusion:In biopsy proven LN, the IBCDT without further immunosuppressive maintenance therapy was shown to be as effective as conventional regimen of MMF or CYC followed by a 3-year maintenance MMF regimen. Moreover, the use of IBCDT was associated with a marked reduction of glucocorticoid cumulative dose.Disclosure of Interests:None declared

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A Prospective Study on Long-Term Clinical Outcomes of Patients with Lupus Nephritis treated with an Intensified B-Cell Depletion Protocol without Maintenance Therapy

Kidney International Reports ◽

10.1016/j.ekir.2021.01.027 ◽

2021 ◽

Author(s):

Dario Roccatello ◽

Savino Sciascia ◽

Carla Naretto ◽

Mirella Alpa ◽

Roberta Fenoglio ◽

...

Keyword(s):

Lupus Nephritis ◽

Maintenance Therapy ◽

Prospective Study ◽

B Cell ◽

Clinical Outcomes ◽

Cell Depletion ◽

B Cell Depletion ◽

A Prospective Study

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B cell depletion therapy in systemic lupus erythematosus: long-term follow-up and predictors of response

Annals of the Rheumatic Diseases ◽

10.1136/ard.2006.067124 ◽

2007 ◽

Vol 66 (9) ◽

pp. 1259-1262 ◽

Cited By ~ 127

Author(s):

K. P Ng ◽

G. Cambridge ◽

M. J Leandro ◽

J. C W Edwards ◽

M. Ehrenstein ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

B Cell ◽

Lupus Erythematosus ◽

Cell Depletion ◽

B Cell Depletion ◽

Systemic Lupus ◽

Predictors Of Response ◽

Long Term Follow Up

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Faculty Opinions recommendation of Long-term maintenance therapy using rituximab-induced continuous B-cell depletion in patients with ANCA vasculitis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718311020.793519121 ◽

2016 ◽

Author(s):

Kenneth Warrington

Keyword(s):

Maintenance Therapy ◽

B Cell ◽

Cell Depletion ◽

B Cell Depletion ◽

Anca Vasculitis ◽

Term Maintenance

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Long-Term Maintenance Therapy Using Rituximab-Induced Continuous B-Cell Depletion in Patients with ANCA Vasculitis

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.07340713 ◽

2014 ◽

Vol 9 (4) ◽

pp. 736-744 ◽

Cited By ~ 68

Author(s):

William F. Pendergraft ◽

Frank B. Cortazar ◽

Julia Wenger ◽

Andrew P. Murphy ◽

Eugene P. Rhee ◽

...

Keyword(s):

Maintenance Therapy ◽

B Cell ◽

Cell Depletion ◽

B Cell Depletion ◽

Anca Vasculitis ◽

Term Maintenance

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P0286B CELL REPOPULATION AFTER REMISSION INDUCTION WITH RITUXIMAB IN NEWLY DIAGNOSED PATIENTS WITH ANCA-ASSOCIATED VASCULITIS: DOES ONE SIZE FIT ALL?

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0286 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Chiara Salviani ◽

Alessandra Gina Gregorini ◽

Guido Jeannin ◽

Federico Alberici ◽

Giovanni Cancarini ◽

...

Keyword(s):

Maintenance Therapy ◽

B Cell ◽

Clinical Diagnosis ◽

Cell Depletion ◽

Remission Induction ◽

B Cell Depletion ◽

Cell Recovery ◽

Anca Associated Vasculitis ◽

Cell Repopulation

Abstract Background and Aims Rituximab (RTX) is one of the mainstays of ANCA-associated vasculitis (AAV) treatment. Nevertheless, studies specifically addressing the B cell repopulation in AAV patients after remission induction with RTX are still scanty and with conflicting results. Moreover, the role of B cell monitoring in the management of RTX-based maintenance therapy still remains to be fully elucidated. In this study, we evaluated B cell repopulation after a single course of RTX in treatment-naïve patients with AAV. Method We included all consecutive patients with new diagnosis of AAV from December 2009 to December 2017, treated with a single course of RTX for remission induction, with a follow-up ≥12 months. B cell recovery, re-treatment for relapse or rise in ANCA titer and scheduled re-treatment were considered as the termination of observation period. B cell count was performed by flow cytometry (Beckman Coulter Navios©) every 2 weeks during the 1st month, every 4 weeks until the 6th month, then every 12 weeks. B cell recovery was defined as CD19 count ≥10 cells/μl. Results Seventy-four patients (38% M, 62% F) met the inclusion criteria. Mean age was 63±21 years. MPA, GPA and EGPA were diagnosed in 49 (66%), 24 (33%) and 1 (1%) patients, respectively. ANCA were positive in 65 (88%) patients, with 50 (68%) anti-MPO and 15 (20%) anti-PR3. Overall median follow-up was 40 months (IQR 25-60). All patients achieved remission and complete B cell depletion after RTX. Twenty-two (31%) patients received plasma-exchange and 20 (29%) steroid pulses. Maintenance therapy with azathioprine or methotrexate was started in 10 (14%) patients. Seventeen (23%) patients received re-treatment with RTX (10 patients for relapses, the remaining cases for B cell recovery and/or a rise in ANCA titre or scheduled re-treatment). B cell recovery was observed in 39 (53%) patients, after a median time of 27 months (IQR 20-38). Particularly, only 7% of patients recovered B cells at 12 months (Figure 1). Univariate analysis showed significant correlation of persistent B-cell depletion with diagnosis of MPA vs GPA (p<0.001), ANCA anti-MPO vs anti-PR3 (p=0.009), higher serum creatinine (p<0.0001) and older age (p=0.004) (Figure 2). Sex, plasma-exchange at induction, steroid pulses, cumulative dose of RTX and maintenance therapy did not affect B cell recovery. Multivariate analysis confirmed significant association between B cell recovery and better renal function (RR 2.655, IC 1.254-5.615, p= 0.011) and clinical diagnosis of GPA (RR 2.466, IC 1.211-5.021, p=0.013). Conclusion After a single course of RTX for remission induction, we observed a very long-lasting B cell depletion in the large majority of our patients. Clinical diagnosis of MPA and a worse renal function were significantly correlated to persistent B cell depletion. These data question the need for scheduled RTX re-treatments in all AAV patients regardless of clinical diagnosis and features.

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Rituximab in Severe Lupus Nephritis: Early B-Cell Depletion Affects Long-Term Renal Outcome

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.04030808 ◽

2009 ◽

Vol 4 (3) ◽

pp. 579-587 ◽

Cited By ~ 100

Author(s):

Catherine Melander ◽

Marion Sallée ◽

Pierre Trolliet ◽

Sophie Candon ◽

Xavier Belenfant ◽

...

Keyword(s):

Lupus Nephritis ◽

B Cell ◽

Cell Depletion ◽

Renal Outcome ◽

B Cell Depletion ◽

Severe Lupus Nephritis

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Long-term effects of combined B-cell immunomodulation with rituximab and belimumab in severe, refractory systemic lupus erythematosus: 2-year results

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa117 ◽

2020 ◽

Author(s):

Tineke Kraaij ◽

Eline J Arends ◽

Laura S van Dam ◽

Sylvia W A Kamerling ◽

Paul L A van Daele ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

B Cells ◽

B Cell ◽

Lupus Erythematosus ◽

Cell Depletion ◽

B Cell Depletion ◽

Systemic Lupus ◽

Anti Cd20

Abstract Background Anti-CD20 B-cell depletion has not shown superior efficacy to standard immunosuppression in patients with systemic lupus erythematosus (SLE). Besides trial design, potential explanations are incomplete B-cell depletion in relation to substantial surges in B-cell-activating factor (BAFF). To improve B-cell targeting strategies, we conducted the first study in SLE patients aimed at investigating immunological effects and feasibility of combining rituximab (RTX; anti-CD20) and belimumab (BLM; anti-BAFF). Methods Reported is the long-term follow-up of a Phase 2 proof-of-concept study in 15 patients with SLE including 12 (80%) with lupus nephritis (LN). Results In 10/15 (67%) patients, a clinical response was observed by achievement of lupus low disease activity state, of which 8 (53%) continued treatment (BLM + ≤7.5 mg prednisolone) for the complete 2 years of follow-up. Five patients (33%) were referred to as ‘non-responders’ due to persistent LN, major flare or repetitive minor flares. Out of 12 LN patients, 9 (75%) showed a renal response including 8 (67%) complete renal responders. All anti-dsDNA+ patients converted to negative, and both anti-C1q and extractable nuclear antigen autoantibodies showed significant reductions. CD19+ B cells showed a median decrease from baseline of 97% at 24 weeks, with a persistent reduction of 84% up to 104 weeks. When comparing responders with non-responders, CD20+ B cells were depleted significantly less in non-responders and double-negative (DN) B cells repopulated significantly earlier. Conclusions Combined B-cell targeted therapy with RTX and BLM prevented full B-cell repopulation including DN B cells, with concomitant specific reduction of SLE-relevant autoantibodies. The observed immunological and clinical benefits in a therapy-refractory SLE population prompt further studies on RTX + BLM.

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Long-term follow-up of the MAINTAIN Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2014-206897 ◽

2015 ◽

Vol 75 (3) ◽

pp. 526-531 ◽

Cited By ~ 68

Author(s):

Farah Tamirou ◽

David D'Cruz ◽

Shirish Sangle ◽

Philippe Remy ◽

Carlos Vasconcelos ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Lupus Nephritis ◽

Positive Predictive Value ◽

Maintenance Therapy ◽

Early Response ◽

Renal Outcome ◽

Proliferative Lupus Nephritis ◽

Long Term Follow Up

ObjectiveTo report the 10-year follow-up of the MAINTAIN Nephritis Trial comparing azathioprine (AZA) and mycophenolate mofetil (MMF) as maintenance therapy of proliferative lupus nephritis, and to test different definitions of early response as predictors of long-term renal outcome.MethodsIn 2014, data on survival, kidney function, 24 h proteinuria, renal flares and other outcomes were collected for the 105 patients randomised between 2002 and 2006, except in 13 lost to follow-up.ResultsDeath (2 and 3 in the AZA and MMF groups, respectively) and end-stage renal disease (1 and 3, respectively) were rare events. Time to renal flare (22 and 19 flares in AZA and MMF groups, respectively) did not differ between AZA and MMF patients. Patients with good long-term renal outcome had a much more stringent early decrease of 24 h proteinuria compared with patients with poor outcome. The positive predictive value of a 24 h proteinuria <0.5 g/day at 3 months, 6 months and 12 months for a good long-term renal outcome was excellent (between 89% and 92%). Inclusion of renal function and urinalysis in the early response criteria did not impact the value of early proteinuria decrease as long-term prognostic marker.ConclusionsThe long-term follow-up data of the MAINTAIN Nephritis Trial do not indicate that MMF is superior to AZA as maintenance therapy in a Caucasian population suffering from proliferative lupus nephritis. Moreover, we confirm the excellent positive predictive value of an early proteinuria decrease for long-term renal outcome.Trial registration numberNCT00204022.

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