A single 4-week course of rituximab was as effective as 18 months of standard therapy with daily oral cyclophosphamide (CyP) and azathioprine (AZA) for induction of remission and maintenance therapy of severe anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The number, rate, and severity of adverse events was similar between the treatment groups, Cees Kallenberg, MD, PhD, professor of clinical immunology at University Medical Center Groningen in Groningen, Netherlands, reported at the 48th Congress of the European Renal Association-European Dialysis and Transplant Association in Prague in June. Rituximab is a monoclonal antibody directed against B lymphocytes.
AAV, an autoimmune disease, affects small blood vessels in multiple organ sites. It can attack the capillaries of the glomeruli, and glomerulonephritis is common in patients with AAV. Left untreated, AAV has a very poor prognosis.
The Rituximab in ANCA-Associated Vasculitis (RAVE) trial tested whether rituximab would be as effective as cyclophosphamide to induce remission of severe AAV. The primary endpoint in the trial was complete remission at 6 months, as measured by a Birmingham vasculitis activity score specific for Wegener’s granulomatosis (BVAS/WG) of 0 and no need for corticosteroids. (WG is one form of AAV.)
Eligible patients had active or severe AAV—either WG or microscopic polyangiitis. The trial design specified that at least half of the participants were to have WG, with a BVAS/WG score of 3 or greater, require cyclophosphamide, and be ANCA-positive at screening. All patients were followed for at least 18 months.
All 200 trial participants initially received 1 to 3 grams of methylprednisolone and were then randomly assigned to a rituximab group or to a CyP/AZA group. The rituximab group received rituximab infusions once weekly for 4 weeks, followed by CyP-placebo for 6 months and AZA-placebo for 12 more months.
The other group took oral CyP daily for 3 to 6 months and rituximab-placebo infusions. For those patients who achieved remission, CyP was replaced by AZA between months 3 and 6 and continued for the remainder of the 18 months. All patients in both groups received daily prednisone, which was tapered over 5.5 months.
If the assigned induction therapy failed, patients were crossed-over to the other treatment. Or if remission was lost for patients while they were taking AZA maintenance therapy, they then received rituximab in an open-label fashion. Analysis of results was on an intention-to-treat basis, meaning participants’ results were analyzed according to the original treatment group to which they were assigned.
The groups were well matched at baseline: two-thirds of the patients were positive for antibodies against proteinase 3 (PR3), one-third for antibodies against myeloperoxidase (MPO), one-quarter had microscopic polyangiitis, and three-quarters had WG. The rituximab (n=99) and CyP/AZA (n=98) groups had similar BVAS/WG scores (5.6–5.7) and scores on the physical and mental components of the SF-36 questionnaire, which profiles functional health and well-being.