B-cell depletion in the treatment of mixed cryoglobulinemia
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- 作者：Domenico Sansonno ; Felicia Anna Tucci ; Michele Montrone ; Laura Troiani ; Loredana Sansonno ; Pietro Gatti ; Gianfranco Lauletta
- 关键词：HCV ; Mixed cryoglobulinemia ; Rituximab
- 刊名：Digestive and Liver Disease
- 出版年：2007
- 出版时间：September 2007
- 年：2007
- 卷：39
- 期：Supplement 1
- 页码：S116-S121
- 全文大小：686 K
文摘
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-α(IFN-α) therapy. They received an intravenous infusion of 375 mg/m2 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.