Rituximab May Be Alternative to Cyclophosphamide for Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Presented at ACR/ARHP
By Liz Meszaros
PHILADELPHIA -- October 20, 2009 -- Rituximab may provide an alternative to cyclophosphamide therapy in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), according to research presented here at the 2009 Annual Scientific Meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP).
For this multicentre, randomised, double-blind, placebo-controlled trial, 197 patients with severe Wegener’s granulomatosis or microscopic polyangiitis were included. Mean Birmingham Vasculitis Activity Score for Wegener’s granulomatosis (BVAS/WG) at enrolment was 8.4. Disease severity, organ involvement, proportion of newly diagnosed disease, AAV type, and ANCA type were similar in both treatment arms.
The purpose of this study, presented here on October 18, was to determine whether treatment with rituximab was not inferior to cyclophosphamide for inducing remission in patients with severe ANCA-associated vasculitis.
Patients were randomised to treatment with rituximab (375 mg/m2 intravenous [IV] at 4 doses weekly) or cyclophosphamide (2 mg/kg/day orally). Once remission was achieved, cyclophosphamide was replaced by azathioprine between months 3 and 6. All patients were given the same glucocorticoid treatment protocol, comprised of methylprednisolone (1 to 3g IV) followed by prednisone (1 mg/kg/day orally), which was reduced to 40 mg/day by month 1, and then tapered and discontinued completely by month 6.
Of the 165 patients who completed 6 months of follow up, a greater proportion of patients in the rituximab arm achieved remission compared with those in the cyclophosphamide group, but the difference was not statistically significant (64% vs 55%, respectively; P = .21). More patients in the rituximab arm achieved a BVAS/WG of 0 and a prednisone dose of <10 mg/day at 6 months compared with those in the cyclophosphamide arm (71% vs 62%; P = .22).
No differences in disease-flare rates were seen between the 2 groups, and the rates of adverse events were similar between the groups as well (.06 vs .08; P = .29). Fewer patients in the rituximab group, however, had 1 or more adverse events (19 vs 32 patients; P = .03).
“Randomisation led to a well-balanced demographic, and we were able to prove the primary hypothesis of the trial, which was that rituximab was not inferior to cyclophosphamide in the induction of remission in patients with AAV,” said coauthor Robert Spiera, MD, Hospital of Special Surgery, New York, New York, who presented the results during a poster session.
“Rituximab represents the first proven alternative to cyclophosphamide in the treatment of AAV. This represents for us a paradigm shift in the treatment of such diseases, and is of particular relevance in patients with severe disease flare,” Dr. Spiera concluded.
[Presentation title: Rituximab Versus Cyclophosphamide for Induction of Remission in ANCA-Associated Vasculitis: A Randomized Controlled Trial (RAVE). Abstract 550]
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