Clinical Trial: Maintenance of ANCA Vasculitis Remission by Intermittent Rituximab Dosing

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Maintenance of ANCA Vasculitis Remission by Intermittent Rituximab Dosing Based on B-cell Reconstitution vs a Serologic ANCA Flare

Brief Summary: The purpose of this study is to determine the best management strategy to maintain remission in patients with ANCA vasculitis who have been treated with rituximab induced B cell depletion for at least two years. This study will compare intermittent B Cell depletion upon B cell return or intermittent B cell depletion upon serologic relapse.

Detailed Summary:

Anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis is a systemic autoimmune disease characterized by small vessel inflammation caused by pathogenic autoantibodies directed against proteinase 3 (PR3) or myeloperoxidase (MPO). Immunosuppressive therapy can result in remission; however, many patients relapse, which results in additional injury.

Rituximab, a humanized murine monoclonal antibody directed against CD20 located on the surface of B-lymphocytes (B cells), is effective in depleting B cells. The RAVE and RITUXVAS trials have shown efficacy of rituximab with steroids for induction of remission in ANCA vasculitis, similar to cyclophosphamide and steroids. Rituximab is now FDA-approved for induction of remission therapy in ANCA vasculitis. The utility of anti-B-cell therapy for early induction of remission in ANCA vasculitis is not surprising given that ANCA are pathogenic in vitro and in vivo. It is clear that remission in many patients is not sustained with a single induction course of rituximab, and relapses often occur after B cell re-population suggesting that scheduled, serial dosing of rituximab could result in sustained remissions.

Despite yielding promising outcomes, rituximab is also associated with a number of adverse events including infectious complications and late onset of neutropenia5, 15. Furthermore, the complications of continuous B cell depletion for extended durations are unknown. One of the major goals in the field is to utilize prolonged B cell depletion only in the subpopulation of patients where the risk of disease relapse outweighs the risk of treatment-related adverse events.

A rise in ANCA titers and reconstitution of B cells are promising biomarkers of impending disease relapse following treatment with rituximab4-6

Same as current

Current Secondary Outcome:

  • Number of serious adverse events [ Time Frame: 3 years ]
  • Composite of disease relapse (defined a BVAS/WG ≥ 2) and serious adverse events [ Time Frame: 3 years ]
  • Hypogammaglobulinemia defined as an IgG < 400 mg/dL [ Time Frame: 3 years ]
  • Patient Survival [ Time Frame: 3 years ]
  • Health-related quality of life as assessed by the Short Form Health Survey (SF-36) score [ Time Frame: 3 years ]
  • Rituximab utilization measured in grams/patient [ Time Frame: 3 years ]
  • Organ damage as assessed by the Vasculitis Damage Index (VDI) [ Time Frame: 3 years ]
  • Number of major relapses defined as a BVAS/WG ≥ 3 [ Time Frame: 3 years ]
  • Number of infections defined as receiving oral or IV antibiotics [ Time Frame: 3 years ]


Original Secondary Outcome: Same as current

Information By: Massachusetts General Hospital

Dates:
Date Received: March 1, 2016
Date Started: June 2016
Date Completion: October 2020
Last Updated: September 21, 2016
Last Verified: September 2016