title: A randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis.
abstract: OBJECTIVE
  To conduct a long-term, prospective, randomized controlled trial evaluating rituximab (RTX) therapy for severe mixed cryoglobulinemia or cryoglobulinemic vasculitis (CV).
  
  
  METHODS
  Fifty-nine patients with CV and related skin ulcers, active glomerulonephritis, or refractory peripheral neuropathy were enrolled. In CV patients who also had hepatitis C virus (HCV) infection, treatment of the HCV infection with antiviral agents had previously failed or was not indicated. Patients were randomized to the non-RTX group (to receive conventional treatment, consisting of 1 of the following 3: glucocorticoids; azathioprine or cyclophosphamide; or plasmapheresis) or the RTX group (to receive 2 infusions of 1 gm each, with a lowering of the glucocorticoid dosage when possible, and with a second course of RTX at relapse). Patients in the non-RTX group who did not respond to treatment could be switched to the RTX group. Study duration was 24 months.
  
  
  RESULTS
  Survival of treatment at 12 months (i.e., the proportion of patients who continued taking their initial therapy), the primary end point, was statistically higher in the RTX group (64.3% versus 3.5% [P < 0.0001]), as well as at 3 months (92.9% versus 13.8% [P < 0.0001]), 6 months (71.4% versus 3.5% [P < 0.0001]), and 24 months (60.7% versus 3.5% [P < 0.0001]). The Birmingham Vasculitis Activity Score decreased only after treatment with RTX (from a mean ± SD of 11.9 ± 5.4 at baseline to 7.1 ± 5.7 at month 2; P < 0.001) up to month 24 (4.4 ± 4.6; P < 0.0001). RTX appeared to be superior therapy for all 3 target organ manifestations, and it was as effective as conventional therapy. The median duration of response to RTX was 18 months. Overall, RTX treatment was well tolerated.
  
  
  CONCLUSIONS
  RTX monotherapy represents a very good option for severe CV and can be maintained over the long term in most patients.
authors.affiliation: Clinic of Rheumatology, AO Universitaria Santa Maria della Misericordia, and University of Udine, Udine, Italy. devita.salvatore@aoud.sanita.fvg.it
authors.forename: S
authors.initials: S
authors.lastname: De Vita
authors.forename: L
authors.initials: L
authors.lastname: Quartuccio
authors.forename: M
authors.initials: M
authors.lastname: Isola
authors.forename: C
authors.initials: C
authors.lastname: Mazzaro
authors.forename: P
authors.initials: P
authors.lastname: Scaini
authors.forename: M
authors.initials: M
authors.lastname: Lenzi
authors.forename: M
authors.initials: M
authors.lastname: Campanini
authors.forename: C
authors.initials: C
authors.lastname: Naclerio
authors.forename: A
authors.initials: A
authors.lastname: Tavoni
authors.forename: M
authors.initials: M
authors.lastname: Pietrogrande
authors.forename: C
authors.initials: C
authors.lastname: Ferri
authors.forename: M T
authors.initials: MT
authors.lastname: Mascia
authors.forename: P
authors.initials: P
authors.lastname: Masolini
authors.forename: A
authors.initials: A
authors.lastname: Zabotti
authors.forename: M
authors.initials: M
authors.lastname: Maset
authors.forename: D
authors.initials: D
authors.lastname: Roccatello
authors.forename: A L
authors.initials: AL
authors.lastname: Zignego
authors.forename: P
authors.initials: P
authors.lastname: Pioltelli
authors.forename: A
authors.initials: A
authors.lastname: Gabrielli
authors.forename: D
authors.initials: D
authors.lastname: Filippini
authors.forename: O
authors.initials: O
authors.lastname: Perrella
authors.forename: S
authors.initials: S
authors.lastname: Migliaresi
authors.forename: M
authors.initials: M
authors.lastname: Galli
authors.forename: S
authors.initials: S
authors.lastname: Bombardieri
authors.forename: G
authors.initials: G
authors.lastname: Monti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003449:Cryoglobulinemia / Q000150:complications / Q000473:pathology / Q000628:therapy*; D003520:Cyclophosphamide / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000187:drug effects; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010956:Plasmapheresis; D012074:Remission Induction; D000069283:Rituximab; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000998:Antiviral Agents; D005938:Glucocorticoids; D007155:Immunologic Factors; D000069283:Rituximab; D003520:Cyclophosphamide; D001379:Azathioprine