Pilot Study of Short-Course Glucocorticoids and Rituximab for Treatment of ANCA-Associated Vasculitis

Phase 4

Completed

Brief Summary: The purpose of this pilot study is to test whether an 8-week course of glucocorticoids, combined with rituximab, is effective in treating ANCA-associated vasculitis.

Detailed Description: The primary aim of this pilot study is to examine whether an 8 week course of glucocorticoids, in combination with rituximab, is effective in inducing and maintaining disease remission for up to 6 months in a subset of patients with ANCA-associated vasculitis (AAV) who have a more favorable prognosis.

This pilot study will enroll 20 patients with active AAV. Close patient follow-up will insure that any patients who require courses of glucocorticoids longer than two months will receive longer therapy, if appropriate for their well-being.

Recruitment & Eligibility

Inclusion Criteria

Patients ages 18-85 years old
Diagnosis of GPA or MPA according to the definitions of the Chapel Hill Consensus Conference
New diagnosis or disease flare with a Birmingham Vasculitis Activity Score/Wegener's granulomatosis (BVAS/WG) of > 3

Exclusion Criteria

Renal disease in patients with PR3-ANCA as defined by any of the following:
Urinary red blood cell casts
Biopsy-proven glomerulonephritis
Increase in serum creatinine of >30% over baseline
Severe renal disease in patients with MPO-ANCA as defined by both of the following:
Urinary red blood cell casts or biopsy-proven glomerulonephritis
Estimated glomerular filtration rate < 30 ml/min/1.73m2
Diffuse alveolar hemorrhage requiring ventilatory support
GC treatment for longer than 14 days prior to enrollment unless patient has been on a stable maintenance dose of prednisone at the time of the flare
Daily oral cyclophosphamide within 1 month prior to enrollment
Completed a remission induction course of cyclophosphamide or rituximab within 4 months of enrollment
Hepatitis B infection
HIV infection
History of anti-GBM disease
Other uncontrolled disease, including drug and alcohol abuse, that may interfere with the study
Pregnancy or breastfeeding
History of severe allergic reactions to human or chimeric monoclonal antibodies

Arm && Interventions

Group	Intervention	Description
Glucocorticoids and Rituximab	Glucocorticoids	This is a single-arm trial. All patients receive both rituximab and glucocorticoids. The protocol calls for the discontinuation of prednisone within two months of the baseline visit.
Glucocorticoids and Rituximab	Rituximab	This is a single-arm trial. All patients receive both rituximab and glucocorticoids. The protocol calls for the discontinuation of prednisone within two months of the baseline visit.

Primary Outcome Measures

Name	Time	Method
Complete Remission	6 months	We examined whether an 8-week glucocorticoid course in combination with rituximab (RTX) would induce disease remission in patients with AAV. The primary outcome was disease remission off steroids at 6 months.

Secondary Outcome Measures

Name	Time	Method
Sustained Complete Remission	6 months	Number of patients entering sustained remission defined as BVAS/WG = 0, prednisone dose = 0 and no disease flares during the study period.
Limited Flares	6 months	Number of limited flares defined as a new occurrence or worsening of one or more minor BVAS/WG items and a total BVAS/WG ≤ 3
Disease Response	4 weeks	Number of patients achieving disease response defined as, no new disease manifestations; no worsening of existing disease; stable or improved BVAS/WG score at 4 weeks.
Early Treatment Failures	4 weeks	Number of early treatment failures defined as patients who have new or worsening disease manifestations assessed at 4 weeks after study entry
Partial Remission	8 weeks	Number of patients entering partial remission, defined as no new disease manifestations, no worsening of existing disease and BVAS/WG \< 3.
Vasculitis Damage Index (VDI)	24 months	The Vasculitis Damage Index (VDI) is a single-page catalog of damage items separated into 11 groupings of items by organ system. There are a total of 60 items. Each item is recorded if it occurred since the onset of vasculitis, has been present for at least 3 months, or occurred at least 3 months ago. Each item of damage is scored as present (1) or absent (0), yielding a maximum score of 60.
Severe Flares	6 months	Number of severe flares defined as flare with BVAS/WG \> 3 or experiencing one of the major BVAS/WG items

Locations (1): Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States