B-cell depletion in the treatment of mixed cryoglobulinemia.
A controlled study has been carried out to assess the efficacy of rituximab (RTX), a chimeric antibody that binds to the B-cell surface antigen CD20, in twenty patients with mixed cryoglobulinemia (MC) and HCV-positive chronic active liver disease, resistant to interferon-alpha (IFN-alpha) therapy. They received an intravenous infusion of 375 mg/m(2) RTX once a week for 4 consecutive weeks. Infusion of RTX had a good safety profile, and no severe side-effects were reported. Sixteen patients (80%) had a complete response (CR), characterized by rapid improvement of clinical signs (disappearance of purpura, weakness, arthralgias and improvement of peripheral neuropathy), and decreased cryocrit. CR was associated with a significant reduction in rheumatoid factor (RF) activity and anti-HCV antibody titers. Decline of IgG anti-HCV titers in the cryoprecipitates was usually associated with a favorable response (r= 0.81; p <0.005). No differences in the dynamics of B-cell depletion and recovery were found between responders and non-responders. Molecular monitoring of the B-cell response revealed disappearance/deletion of peripheral clones in the responders and great stability in the non-responders. RTX had a deep impact on hepatitis C viremia: HCV RNA increased to approximately twice the baseline level in the responders, whereas it remained much the same in the non-responders. Twelve out of 16 responders (75%) remained in remission throughout the follow-up. The results indicate that RTX has clinical and biological activity in HCV-positive MC patients. However, in view of the increased viremia in the responders, additional modes of application and combination of RTX with other agents need to be investigated.
Sansonno
Domenico
D
Department of Biomedical Seiences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical Sehool, Bari, Italy. d.sansonno@dimo.uniba.it
Tucci
Felicia Anna
FA
Montrone
Michele
M
Troiani
Laura
L
Sansonno
Loredana
L
Gatti
Pietro
P
Lauletta
Gianfranco
G
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000998:Antiviral Agents / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000276:immunology*; D003449:Cryoglobulinemia / Q000628:therapy*; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage; D000069283:Rituximab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000998:Antiviral Agents; D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000069283:Rituximab; C100416:peginterferon alfa-2a