title: A 4-year observation in lupus nephritis patients treated with an intensified B-lymphocyte depletion without immunosuppressive maintenance treatment-Clinical response compared to literature and immunological re-assessment.
abstract: BACKGROUND
  B cells (BC) play a critical role in systemic lupus erythematosus (SLE). BC depletion therapy still remains an attractive option, despite the disappointing results of randomized controlled trials (RTCs).
  
  
  METHODS
  Twelve patients with SLE [3 males, mean age 43.8 yrs (25-55)] with severe multiorgan involvement all including kidney (3 patients with Class IV, 4 with Class III/V and 5 with Class V, according to the International Society of Nephrology/Renal Pathology Society glomerulonephritis classification), skin lesions [10], severe polyarthralgias with arthritis [10], polyserositis [2], and lymphadenopathy [5] have been prospectively treated with an intensified B cell depletion therapy (IBCDT) protocol due to their resistance or intolerance to previous therapy (six cases) or as a front line immunosuppressive treatment in 6 women with unsatisfactory therapeutic compliance or as a specific request of a short-time immunosuppression for gestational perspectives.
  
  
  METHODS
  Rituximab (RTX) 375 mg/sm on days 1, 8, 15, 22, and 2 more doses after 1 and 2 months, associated with 2 IV administrations of 10mg/kg of cyclophosphamide and 3 methylprednisolone pulses (15mg/kg) followed by oral prednisone (0.8 mg/kg/day, rapidly tapered to 5mg/day by the end of the 3rd month after RTX). No further immunosuppressive maintenance therapy has been given.
  
  
  RESULTS
  Patients had been followed-up for a mean of 44.5 (24-93)months. Significant decreases (p<0.05) were found in the levels of ESR (baseline mean value: 55.0mm; 3 months: 36; end of follow-up: 13), anti-dsDNA antibodies (baseline: 185 U; 3 months: 107; end of follow-up: 15), and proteinuria (baseline: 4.9 g/24h; 3 months: 0.97; end of follow-up: 0.22). C4 values (baseline 11 mg/dl) significantly increased (p<0.05) after 3 months (22 mg/dl) and at the end of the follow-up (20mg/dl). Of the 12 patients, 9 (75%) have remained well after one cycle of IBCDT, with no flare (mean 51.6 months [25-93]). Three patients relapsed after 36, 41, and 72 months, respectively. Following re-treatment, they again showed complete remission over 18-48 months of observation.
  
  
  CONCLUSIONS
  A promising role of RTX in an intensified protocol of induction therapy can be envisaged in patients for whom avoiding immunosuppressive maintenance therapy and sparing steroids are particularly appealing. Moreover, our data confirm in one of the longest follow-up available, the opportunity to reconsider the regimens of BL depletion in the treatment of the most severe or refractory forms of SLE despite the disappointing results of RCTs.
authors.affiliation: Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy; SCDU Nephrology and Dialysis, S. Giovanni Bosco Hospital, Turin, Italy. Electronic address: dario.roccatello@unito.it.
authors.forename: Dario
authors.initials: D
authors.lastname: Roccatello
authors.affiliation: Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy.
authors.forename: Savino
authors.initials: S
authors.lastname: Sciascia
authors.affiliation: Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Baldovino
authors.affiliation: Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rossi
authors.affiliation: Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Alpa
authors.affiliation: Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Naretto
authors.affiliation: Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy.
authors.forename: Debora
authors.initials: D
authors.lastname: Di Simone
authors.affiliation: Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Simoncini
authors.affiliation: Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Menegatti
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D002986:Clinical Trials as Topic; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008181:Lupus Nephritis / Q000188:drug therapy / Q000276:immunology*; D008212:Lymphocyte Depletion; D064887:Observational Studies as Topic
chemical_list: D007166:Immunosuppressive Agents