title: Efficacy and safety of rituximab second-line therapy for membranous nephropathy: a prospective, matched-cohort study.
abstract: OBJECTIVE
  First-line immunosuppression with the B-cell depleting antibody rituximab reduced proteinuria and induced remission of the disease in patients with nephrotic syndrome (NS) secondary to idiopathic membranous nephropathy (IMN). Here we evaluated whether rituximab is equally effective in patients who failed to respond to previous immunosuppressive treatment.
  
  
  METHODS
  This academic, matched-cohort study, compared 2-year outcomes of 11 consecutive IMN patients who received second-line rituximab therapy for NS persisting or relapsing after previous treatment with steroids alone or combined with alkylating agents, cyclosporine, or immunoglobulin G, with those of 11 age- (± 5 years), gender- and proteinuria- (± 1 g/24h) matched reference patients given first-line rituximab therapy.
  
  
  RESULTS
  Patients' and reference patients' baseline characteristics were similar. Compared to baseline, 24-hour proteinuria similarly declined at 1 and 2 years post-rituximab (by 50.5 ± 25.1% and 60.9 ± 17.4% in patients and by 52.7 ± 31.5% and 69.4 ± 40.4% in reference patients, respectively; p < 0.01 for all comparisons vs. baseline). 8 patients and 7 reference patients achieved full (3 vs. 2) or partial (5 per cohort) proteinuria remission. Hypoalbuminemia and hyperlipidemia normalized in both groups. Self-limited infusion-related reactions occurred in 1 subject per cohort.
  
  
  CONCLUSIONS
  Rituximab reduced proteinuria in IMN patients with no or only transient response to unselective immunosuppression as effectively and safely as in patients without previous immunosuppression.
authors.affiliation: Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Cravedi
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Sghirlanzoni
authors.forename: Maddalena
authors.initials: M
authors.lastname: Marasà
authors.forename: Alessandra
authors.initials: A
authors.lastname: Salerno
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
mesh_terms: D000328:Adult; D000477:Alkylating Agents / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D001706:Biopsy; D015331:Cohort Studies; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007155:Immunologic Factors / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011507:Proteinuria / Q000097:blood; D012074:Remission Induction; D000069283:Rituximab
chemical_list: D000477:Alkylating Agents; D058846:Antibodies, Monoclonal, Murine-Derived; D007074:Immunoglobulin G; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000069283:Rituximab; D016572:Cyclosporine