PIRR therapy in HCV-related mixed cryoglobulinemia

Abstract

With few exceptions, a close association between HCV infection and mixed cryoglobulinemia (MC) has been definitively established. In HCV chronically infected patients, and hence for HCV-positive MC patients as well, pegylated interferon-α (pIFN-α) plus ribavirin (RBV) combined therapy has become the standard of care. More recently, the efficacy and safety of rituximab (RTX), an anti-CD20 chimeric monoclonal antibody, have been shown in MC patients resistant or intolerant to combined therapy; however, enhanced HCV RNA levels have often been detected following RTX administration. Thus, we tested the effectiveness and tolerability of pIFN-α plus RBV plus RTX, a combination (PIRR). A complete response was achieved in 54.5% of MC patients treated with the PIRR combination (study arm) and in 33.3% of those receiving pIFN-α plus RBV, the standard of care (control arm). The successful response was maintained for up to 36 months in over 83% of patients in the study arm, but in only 40% of those enrolled in the control arm. No serious adverse events were recorded, although acute and medium- to long-term side effects have been described in a very few patients given RTX for MC or other indications. Additional studies addressing issues such as the pharmacokinetic behavior of RTX, the best sequence of PIRR drug administration, optimal doses of the drugs as a function of HCV genotype, and therapeutic combinations including new protease inhibitors and new anti-CD20 monoclonal antibodies, will hopefully improve the overall results.