These data indicate that therapy with rituximab is able to induce remission in a high percentage of patients, and that remission can be sustained beyond 6 months despite the presence of continuing HCV infection.
The current investigation was based upon the hypothesis that rituximab-induced depletion of the expanded population of autoreactive B cells would decrease pathogenic cryoglobulin formation and result in clinical improvement in the vasculitis.
Depletion of peripheral blood B cells was observed in all patients who received four infusions of rituximab. B cell depletion was associated with a decrease in cryoglobulin levels and improvement in vasculitis activity. A return of B cells to pre-treatment levels occurred within 6–8 months, but this did not correlate with a relapse of disease activity.
Although most patients remained in remission for months after the return of peripheral B cells, the persistence of low-level cryoglobulinemia and ongoing HCV infection suggests that rituximab treatment did not eradicate the pathogenic B cell population and these patients remain at risk for future relapse.
... Our study only enrolled patients in whom antiviral therapy failed to induce remission either because a lack of sustained virologic response or regimen related toxicity. Limiting our study to such patients made it possible to assess the efficacy, toxicity, and effect on the underlying HCV infection of rituximab without the confounders of concomitant antiviral therapy.
Recent studies suggest that combining rituximab with interferon-based antiviral therapy results in improved response rates compared to antiviral therapy alone (17, 25) a hypothesis which cannot be directly addressed by our trial.In conclusion, our data suggests that rituximab can induce sustained remissions in patients with HCV-associated cryoglobulinemic vasculitis following failure of antiviral therapy. Rituximab treatment was well tolerated and did not appear to increase HCV replication or worsen the underlying hepatitis.
