title: Rituximab combined with Peg-interferon-ribavirin in refractory hepatitis C virus-associated cryoglobulinaemia vasculitis.
abstract: OBJECTIVE
  To report the results of a pilot study using rituximab combined with Peg-interferon (IFN) alpha2b-ribavirin in severe refractory hepatitis C virus (HCV) related mixed cryoglobulinaemia (MC) vasculitis.
  
  
  METHODS
  Sixteen consecutive patients with severe HCV-MC vasculitis that were resistant (n = 11) or relapser (n = 5) to a previous combination treatment with standard (n = 10) or Peg-IFNalpha2b (n = 6) plus ribavirin were included. They were treated with rituximab (375 mg/m2 intravenously weekly for 4 weeks) combined with Peg-IFNalpha2b (1.5 mug/kg per week subcutaneously) plus ribavirin (600-1200 mg/day orally) for 12 months.
  
  
  RESULTS
  Fifteen patients (93.7%) showed clinical improvement, 10 of whom (62.5%) were clinical complete responders (CR). HCV RNA and serum cryoglobulin became undetectable in all the clinical CR. Peripheral blood B cell depletion was achieved in all patients (CD19+ cells, 111 (SD 32)/mm3 at baseline versus 2(2)/mm3 after the fourth infusion of rituximab) with reconstitution starting at the end of antiviral treatment. Compared with clinical CR, the partial or non-responders had a 3.6 times longer duration of vasculitis prior to treatment and a lower rate of early virological response. Treatment was well tolerated with no infectious complications. After a mean follow-up of 19.4 (SD 3.6) months, two patients experienced clinical relapse associated with a simultaneous reappearance of HCV RNA and cryoglobulin and an increase in the number of B cells.
  
  
  CONCLUSIONS
  Rituximab combined with Peg-IFNalpha2b-ribavirin represents a safe and effective treatment option in severe refractory HCV-MC vasculitis.
authors.affiliation: Pierre et Marie Curie-Paris 6, University 1, CNRS, UMR 7087, Paris, F-75013 France. patrice.cacoub@psl.aphp.fr
authors.forename: D
authors.initials: D
authors.lastname: Saadoun
authors.forename: M
authors.initials: M
authors.lastname: Resche-Rigon
authors.forename: D
authors.initials: D
authors.lastname: Sene
authors.forename: L
authors.initials: L
authors.lastname: Perard
authors.forename: A
authors.initials: A
authors.lastname: Karras
authors.forename: P
authors.initials: P
authors.lastname: Cacoub
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000998:Antiviral Agents / Q000627:therapeutic use*; D003449:Cryoglobulinemia / Q000150:complications / Q000188:drug therapy; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D000069283:Rituximab; D016896:Treatment Outcome; D014657:Vasculitis / Q000188:drug therapy* / Q000821:virology
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000069283:Rituximab; C417083:peginterferon alfa-2b