TY - JOUR
T1 - Monoclonal antibody treatment of mixed cryoglobulinemia resistant to interferon α with an anti-CD20
AU - Sansonno, Domenico
AU - De Re, Valli
AU - Lauletta, Gianfranco
AU - Tucci, Felicia Anna
AU - Boiocchi, Mauro
AU - Dammacco, Franco
PY - 2003/5/15
Y1 - 2003/5/15
N2 - A controlled study has been carried out to assess the efficacy of rituximab, a chimeric antibody that binds to the B-cell surface antigen CD20, in 20 patients with mixed cryoglobulinemia (MC) and hepatitis C virus (HCV)-positive chronic active liver disease, resistant to interferon α (IFN-α) therapy. They received an intravenous infusion of 375 mg/m2 rituximab once a week for 4 consecutive weeks. Infusion of rituximab had a good safety profile and no severe side effects were reported. Sixteen patients (80%) showed a complete response (CR), characterized by rapid improvement of clinical signs (disappearance of purpura and weakness arthralgia and improvement of peripheral neuropathy), and decline of cryocrit. CR was associated with a significant reduction of 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 <.005). No differences in the dynamics of B-cell depletion and recovery were found between responders and nonresponders. Molecular monitoring of the B-cell response revealed disappearance/deletion of peripheral clones in the responders and great stability in the nonresponders. Rituximab had a deep impact on hepatitis C viremia; HCV RNA increased approximately twice the baseline levels in the responders, whereas it remained much the same in the nonresponders. Twelve (75%) of 16 responders remained in remission throughout the follow-up. The results indicate that rituximab has clinical and biologic activity in patients with HCV+ MC. However, in view of the increased viremia in the responders, additional modes of application and combination of rituximab with other agents need to be investigated.
AB - A controlled study has been carried out to assess the efficacy of rituximab, a chimeric antibody that binds to the B-cell surface antigen CD20, in 20 patients with mixed cryoglobulinemia (MC) and hepatitis C virus (HCV)-positive chronic active liver disease, resistant to interferon α (IFN-α) therapy. They received an intravenous infusion of 375 mg/m2 rituximab once a week for 4 consecutive weeks. Infusion of rituximab had a good safety profile and no severe side effects were reported. Sixteen patients (80%) showed a complete response (CR), characterized by rapid improvement of clinical signs (disappearance of purpura and weakness arthralgia and improvement of peripheral neuropathy), and decline of cryocrit. CR was associated with a significant reduction of 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 <.005). No differences in the dynamics of B-cell depletion and recovery were found between responders and nonresponders. Molecular monitoring of the B-cell response revealed disappearance/deletion of peripheral clones in the responders and great stability in the nonresponders. Rituximab had a deep impact on hepatitis C viremia; HCV RNA increased approximately twice the baseline levels in the responders, whereas it remained much the same in the nonresponders. Twelve (75%) of 16 responders remained in remission throughout the follow-up. The results indicate that rituximab has clinical and biologic activity in patients with HCV+ MC. However, in view of the increased viremia in the responders, additional modes of application and combination of rituximab with other agents need to be investigated.
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U2 - 10.1182/blood-2002-10-3162
DO - 10.1182/blood-2002-10-3162
M3 - Article
C2 - 12506023
AN - SCOPUS:0038603204
VL - 101
SP - 3818
EP - 3826
JO - Blood
JF - Blood
SN - 0006-4971
IS - 10
ER -