A phase II, single-arm multicenter study of low-dose rituximab for refractory mixed cryoglobulinemia secondary to hepatitis C virus infection

Autoimmun Rev. 2011 Sep;10(11):714-9. doi: 10.1016/j.autrev.2011.04.033. Epub 2011 May 5.

Abstract

Eradication of hepatitis C virus (HCV) by antiviral therapy is the treatment of choice for mixed cryoglobulinemia secondary to this infection, but many patients fail to achieve sustained viral responses and need second-line treatments. Several studies have demonstrated that the infusion of the anti-CD20 monoclonal antibody rituximab is highly effective for refractory mixed cryoglobulinemia, with a clinical response in approximately 80% of patients, although the relapse rate is high. Virtually all published studies employed a rituximab dosage of 375mg/m(2) given four times, a schedule used for treating non-Hodgkin's lymphomas. Based on a prior pilot study, we designed a phase II single-arm two-stage study (EUDRACT n. 2008-000086-38) to evaluate the efficacy of a lower dosage of rituximab, 250mg/m(2) given twice, for refractory mixed cryoglobulinemia. We present here the preliminary results in the first 27 patients enrolled. The overall response rate in 24 evaluable patients was 79%, and the mean time to relapse was 6.5months, similar to the 6.7months reported in studies with high-dose rituximab. Side effects were comparable to those seen in patients treated with high-dose. Increase of HCV viral load, reported in some high-dose studies, was not observed in our patients. Low-dose rituximab may provide a more cost/effective and possibly safer alternative for treating refractory HCV-associated mixed cryoglobulinemia.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage*
  • Antibodies, Monoclonal, Murine-Derived / adverse effects
  • Antiviral Agents / administration & dosage
  • Clinical Protocols
  • Cost-Benefit Analysis
  • Cryoglobulinemia / drug therapy*
  • Cryoglobulinemia / economics
  • Cryoglobulinemia / etiology
  • Cryoglobulinemia / physiopathology
  • Drug Resistance
  • Female
  • Follow-Up Studies
  • Hepatitis C / complications
  • Hepatitis C / drug therapy*
  • Hepatitis C / economics
  • Hepatitis C / physiopathology
  • Humans
  • Italy
  • Male
  • Middle Aged
  • Recurrence
  • Remission Induction
  • Rituximab

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antiviral Agents
  • Rituximab