title: Efficacy of low-dose rituximab for the treatment of mixed cryoglobulinemia vasculitis: Phase II clinical trial and systematic review.
abstract: OBJECTIVE
  To evaluate whether rituximab at a low dose of 250 mg/m(2) × 2 may be as effective as at higher dosages, most commonly 375 mg/m(2)×4, used in previous studies on the treatment of patients with refractory mixed cryoglobulinemia (MC) vasculitis associated with hepatitis C virus (HCV) infection.
  
  
  METHODS
  We conducted a phase 2, single-arm two-stage trial (EUDRACT n. 2008-000086-38) of low-dose rituximab in 52 patients with HCV-associated MC who were ineligible/intolerant or non-responder to antiviral therapy. The primary outcomes were response of vasculitis evaluated by the Birmingham Vasculitis Activity Score (BVAS) at months 3, 6 and 12, rate of relapses and time to relapse, and rate of adverse events. Our data were compared with those reported in 19 published studies selected among 291 reviewed in a literature search.
  
  
  RESULTS
  The cumulative response rate (complete and partial) at month 3 was 81% in our patients, and 86% in 208 patients from studies using high-dose rituximab. The relapse rate and median time to relapse were, respectively, 41% and 6 months in our study, and 32% and 7 months in high-dose studies. Treatment-related adverse events were 11.5% in our study and 19.9% in high-dose studies. None of these differences was statistically significant.
  
  
  CONCLUSIONS
  Rituximab at a low dosage of 250 mg/m(2) × 2 is as effective as at higher dosages for treating MC vasculitis. This low-dose regimen may improve the cost/benefit profile of rituximab therapy for MC.
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy. Electronic address: marcella.visentini@uniroma1.it.
authors.forename: Marcella
authors.initials: M
authors.lastname: Visentini
authors.affiliation: Clinical Epidemiology and Biometric Unit, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Tinelli
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Colantuono
authors.affiliation: Research Center for Systemic Manifestations of Hepatitis Viruses, Department of Internal Medicine, University of Firenze, Firenze, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Monti
authors.affiliation: Infectious Diseases Research Laboratories, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Ludovisi
authors.affiliation: Research Center for Systemic Manifestations of Hepatitis Viruses, Department of Internal Medicine, University of Firenze, Firenze, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Gragnani
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Milica
authors.initials: M
authors.lastname: Mitrevski
authors.affiliation: Research Center for Systemic Manifestations of Hepatitis Viruses, Department of Internal Medicine, University of Firenze, Firenze, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Ranieri
authors.affiliation: Research Center for Systemic Manifestations of Hepatitis Viruses, Department of Internal Medicine, University of Firenze, Firenze, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Fognani
authors.affiliation: Research Center for Systemic Manifestations of Hepatitis Viruses, Department of Internal Medicine, University of Firenze, Firenze, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Piluso
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Granata
authors.affiliation: Clinical Epidemiology and Biometric Unit, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: De Silvestri
authors.affiliation: Clinical Epidemiology and Biometric Unit, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Scotti
authors.affiliation: Infectious Diseases Research Laboratories, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
authors.forename: Mario U
authors.initials: MU
authors.lastname: Mondelli
authors.affiliation: Research Center for Systemic Manifestations of Hepatitis Viruses, Department of Internal Medicine, University of Firenze, Firenze, Italy.
authors.forename: Anna Linda
authors.initials: AL
authors.lastname: Zignego
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Fiorilli
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Milvia
authors.initials: M
authors.lastname: Casato
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D003362:Cost-Benefit Analysis; D003449:Cryoglobulinemia / Q000150:complications / Q000188:drug therapy; D012008:Recurrence; D000069283:Rituximab / Q000008:administration & dosage / Q000627:therapeutic use; D014657:Vasculitis / Q000150:complications
chemical_list: D000069283:Rituximab
keywords: Low-dose; Mixed cryoglobulinemia; Rituximab