Rituximab versus cyclophosphamide for ANCA-associated vasculitis.
Author(s): Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CG, St
Clair EW, Turkiewicz A, Tchao NK, Webber L, Ding L, Sejismundo LP, Mieras K,
Weitzenkamp D, Ikle D, Seyfert-Margolis V, Mueller M, Brunetta P, Allen NB,
Fervenza FC, Geetha D, Keogh KA, Kissin EY, Monach PA, Peikert T, Stegeman C,
Ytterberg SR, Specks U; RAVE-ITN Research Group.
Collaborators: Specks U, Stone JH, Specks U, Ytterberg SR, Fervenza FC, Keogh KA,
Peikert T, Golbin JM, Klein L, Mieras K, Beinhorn C, Fisher S, Clawson ML, Bendel
S, Hummel AM, Merkel PA, Kissin EY, Monach PA, Clark-Cotton MR, McAlear CA,
Pettit JL, Sutton MB, Widom RL, Farina GA, DiMarzio MJ, Johnson SP, Schiller
Patel A, Seo P, Stone JH, Hellmann D, Geetha D, Saleh A, Wung P, Sejismundo LP,
Humphrey C, Marriott M, Goldsborough Y, Pinachos A, Gauss K, King L, Langford CA,
Hoffman GS, Hajj-Ali RA, Carey JJ, Molloy ES, Koening CL, Bork D, Clark TM,
Tuthill KA, Markle T, Petrich J, Spiera R, Alpert DR, DiMartino SJ, Gordon JK,
Moskowitz NK, Kirou KA, Samuels J, Kloiber SA, Julevic E, O'Donohue M, Patel A,
Kallenberg CG, Stegeman C, Rasker P, Mulder K, Limburg P, Kosterink J, St Clair
EW, Allen NB, Scarlett E, Tochacek M, Turkiewicz A, Fessler B, Chatham W, Turner
A, Ikle D, Weitzenkamp D, Wu W, D'Lugin T, Jacob C, Webber L, Ding L, Adah S,
Tchao NK, Mueller M, Bourcier K, Asare A, Seyfert-Margolis V, Tosta P, Skeeter
NB, Anderson CL, Archampong AN.
Affiliation(s): Massachusetts General Hospital, Boston, USA.
Publication date & source: 2010, N Engl J Med. , 363(3):221-32
BACKGROUND: Cyclophosphamide and glucocorticoids have been the cornerstone of
remission-induction therapy for severe antineutrophil cytoplasmic antibody
(ANCA)-associated vasculitis for 40 years. Uncontrolled studies suggest that
rituximab is effective and may be safer than a cyclophosphamide-based regimen.
METHODS: We conducted a multicenter, randomized, double-blind, double-dummy,
noninferiority trial of rituximab (375 mg per square meter of body-surface area
per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of
body weight per day) for remission induction. Glucocorticoids were tapered off;
the primary end point was remission of disease without the use of prednisone at 6
months.
RESULTS: Nine centers enrolled 197 ANCA-positive patients with either Wegener's
granulomatosis or microscopic polyangiitis. Baseline disease activity, organ
involvement, and the proportion of patients with relapsing disease were similar
in the two treatment groups. Sixty-three patients in the rituximab group (64%)
reached the primary end point, as compared with 52 patients in the control group
(53%), a result that met the criterion for noninferiority (P<0.001). The
rituximab-based regimen was more efficacious than the cyclophosphamide-based
regimen for inducing remission of relapsing disease; 34 of 51 patients in the
rituximab group (67%) as compared with 21 of 50 patients in the control group
(42%) reached the primary end point (P=0.01). Rituximab was also as effective as
cyclophosphamide in the treatment of patients with major renal disease or
alveolar hemorrhage. There were no significant differences between the treatment
groups with respect to rates of adverse events.
CONCLUSIONS: Rituximab therapy was not inferior to daily cyclophosphamide
treatment for induction of remission in severe ANCA-associated vasculitis and may
be superior in relapsing disease. (Funded by the National Institutes of Allergy
and Infectious Diseases, Genentech, and Biogen; ClinicalTrials.gov number,
NCT00104299.)
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