A randomized controlled trial of rituximab following failure of antiviral therapy for hepatitis C virus-associated cryoglobulinemic vasculitis

Abstract

Objective: To perform a randomized controlled trial of rituximab in patients with hepatitis C virus (HCV)-associated mixed cryoglobulinemic vasculitis.

Methods: We conducted a single-center, open-label, randomized controlled trial of rituximab (375 mg/ m(2) /week for 4 weeks) compared to the best available therapy (maintenance or increase in immunosuppressive therapy) for HCV-associated cryoglobulinemic vasculitis in patients in whom antiviral therapy had failed to induce remission. The primary end point was disease remission at 6 months from study entry.

Results: A total of 24 patients were enrolled (12 in each treatment group). Baseline disease activity and organ involvement were similar in the two groups. Ten patients in the rituximab group (83%) were in remission at study month 6, as compared with 1 patient in the control group (8%), a result that met the criterion for stopping the study (P < 0.001). The median duration of remission for rituximab-treated patients who reached the primary end point was 7 months. No adverse effects of rituximab on HCV plasma viremia or on hepatic transaminase levels were observed.

Conclusion: Rituximab was a well-tolerated and effective treatment in patients with HCV-associated cryoglobulinemic vasculitis in whom antiviral therapy failed to induce remission.

Trial registration: ClinicalTrials.gov NCT00029107.

Figure 1

BVAS Scores and Duration of Remission. Panel A shows box plots of BVAS scores during the 6-month study period for patients in the control and rituximab groups. The horizontal line within each box indicates the median value; the bottom and top lines of the box depict the 25^th and 75^th quartiles, respectively; the whiskers show the maximum and minimum values within 1.5 interquartile ranges from the 25^th and 75^th quartiles, respectively; the circles represent values outside the range and considered outliers. Panel B shows the Kaplan-Meier curve for duration of remission among subjects reaching remission under rituximab treatment. The solid lines give the percentage of subjects remaining in remission and the broken lines the 95% confidence intervals. Only a single patient in the control group achieved remission (data not plotted).

Figure 2

Cryoglobulin Levels. Box plots of cryoglobulin levels (expressed as percent of cryoprecipitate) during the 6-month study period (normal value is <3%). Interpretation of the box plots are the same as in Figure 1A.

Figure 3

Median change in HCV plasma viral levels from baseline in log10 scale. Only data through month 6 are shown for the control group as 9 of these patients subsequently received rituximab after month 6 on the extension phase of the study.