Kidney Week

Abstract: SA-PO257

Design of the Maintenance of ANCA Vasculitis Remission by Intermittent Rituximab Dosing Based on B Cell Reconstitution versus a Serologic ANCA Flare (MAINTANCAVAS) Trial

Session Information

• Clinical Glomerular Disorders: Vasculitis, C3G, IgAN
  November 04, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Glomerular

• 1005 Clinical Glomerular Disorders

Authors

• Cortazar, Frank B., Massachusetts General Hospital, Boston, Massachusetts, United States

Frank B. Cortazar,

• Pendergraft, William Franklin, University of North Carolina Kidney Center, Chapel Hill, North Carolina, United States

William Franklin Pendergraft,

• Dunbar, Colleen B, Massachusetts General Hospital, Boston, Massachusetts, United States

Colleen B Dunbar,

• Laliberte, Karen A., Massachusetts General Hospital, Boston, Massachusetts, United States

Karen A. Laliberte,

• Niles, John, Massachusetts General Hospital, Boston, Massachusetts, United States

John Niles,

Background

B cell depletion with rituximab (RTX) is an effective strategy for maintenance of remission in ANCA vasculitis. Unfortunately, cessation of therapy is associated with a high rate of relapse, while indefinite continuation of fixed-dose treatment is associated with significant complications. No clinical trial data exists to guide the optimal use of RTX after two years of maintenance therapy. To address this unmet need, we designed the MAINTANCAVAS Trial.

Methods

The MAINTANCAVAS Trial is an open-label, randomized, and two-arm controlled trial to evaluate the efficacy of two RTX dosing strategies to prevent disease relapse: 1) RTX dosing upon B cell reconstitution (B cell arm), and 2) RTX dosing upon a significant rise in ANCA titer (ANCA arm). Eligible patients have a history of ANCA vasculitis and have completed at least 24 months of fixed-interval (i.e., every 4-6 months) RTX maintenance therapy in remission (BVAS-WG=0 and prednisone ≤ 7.5 mg/day). Upon randomization, patients discontinue fixed-interval RTX and are followed with clinical assessment and laboratory monitoring every three months. Patients assigned to the B cell arm are re-dosed with RTX 1 gm x 1 when the CD20 count rises above 10 cells/mm³, while patients in the ANCA arm are re-dosed with RTX 1 gm x 2 (separated by 2 weeks) when the ANCA titer rises by pre-specified level. The primary outcome is disease relapse at 36 months. Secondary outcomes include significant adverse events, vasculitis damage, and RTX utilization. At an alpha level of 0.05 and power of 0.80, 180 patients are required to detect a 15% difference in relapse between the strategies.

Results

Enrollment commenced 6/7/2016. To date, a total of 43 patients have been enrolled. No relapses have occurred. Six patients in the B cell arm (n=22) have been re-dosed with RTX at the following times: 6 months (n=2), 9 months (n=3), and 1 year (n=1). No patients in the ANCA arm have been re-dosed. There have been no serious adverse events.

Conclusion

The optimal long-term RTX dosing strategy for maintenance of remission in ANCA vasculitis remains unknown. The MAINTANCAVAS trial should provide useful information to address this important question.