Efficacy of Remission-Induction Regimens for ANCA-Associated Vasculitis

Ulrich Specks; Peter A. Merkel; Philip Seo; Robert Spiera; Carol A. Langford; Gary S. Hoffman; Cees G. M. Kallenberg; E. William St. Clair; Barri J. Fessler; Linna Ding; Lisa Viviano; Nadia K. Tchao; Deborah J. Phippard; Adam L. Asare; Noha Lim; David Ikle; Brett Jepson; Paul Brunetta; Nancy B. Allen; Fernando C. Fervenza; Duvuru Geetha; Karina Keogh; Eugene Y. Kissin; Paul A. Monach; Tobias Peikert; Coen Stegeman; Steven R. Ytterberg; Mark Mueller; Lourdes P. Sejismundo; Kathleen Mieras; John H. Stone; RAVE-ITN Res Grp

doi:10.1056/NEJMoa1213277

Efficacy of Remission-Induction Regimens for ANCA-Associated Vasculitis

Ulrich Specks, Peter A. Merkel, Philip Seo, Robert Spiera, Carol A. Langford, Gary S. Hoffman, Cees G. M. Kallenberg, E. William St. Clair, Barri J. Fessler, Linna Ding, Lisa Viviano, Nadia K. Tchao, Deborah J. Phippard, Adam L. Asare, Noha Lim, David Ikle, Brett Jepson, Paul Brunetta, Nancy B. Allen, Fernando C. FervenzaDuvuru Geetha, Karina Keogh, Eugene Y. Kissin, Paul A. Monach, Tobias Peikert, Coen Stegeman, Steven R. Ytterberg, Mark Mueller, Lourdes P. Sejismundo, Kathleen Mieras, John H. Stone^*, RAVE-ITN Res Grp

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

415 Citations (Scopus)

Abstract

Background

The 18-month efficacy of a single course of rituximab as compared with conventional immunosuppression with cyclophosphamide followed by azathioprine in patients with severe (organ-threatening) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is unknown.

Methods

In a multicenter, randomized, double-blind, double-dummy, noninferiority trial, we compared rituximab (375 mg per square meter of body-surface area administered once a week for 4 weeks) followed by placebo with cyclophosphamide administered for 3 to 6 months followed by azathioprine for 12 to 15 months. The primary outcome measure was complete remission of disease by 6 months, with the remission maintained through 18 months.

Results

A total of 197 patients were enrolled. As reported previously, 64% of the patients in the rituximab group, as compared with 53% of the patients in the cyclophosphamide-azathioprine group, had a complete remission by 6 months. At 12 and 18 months, 48% and 39%, respectively, of the patients in the rituximab group had maintained the complete remissions, as compared with 39% and 33%, respectively, in the comparison group. Rituximab met the prespecified criteria for noninferiority (P

Conclusions

In patients with severe ANCA-associated vasculitis, a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for the induction and maintenance of remissions over the course of 18 months. (Funded by the National Institute of Allergy and Infectious Diseases and others; RAVE ClinicalTrials.gov number, .)

Original language	English
Pages (from-to)	417-427
Number of pages	11
Journal	New England Journal of Medicine
Volume	369
Issue number	5
DOIs	https://doi.org/10.1056/NEJMoa1213277
Publication status	Published - 1-Aug-2013

Keywords

ANTIBODY-ASSOCIATED VASCULITIS
ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES
WEGENERS-GRANULOMATOSIS
RANDOMIZED-TRIAL
SYSTEMIC VASCULITIDES
RENAL VASCULITIS
CELL-ACTIVATION
CYCLOPHOSPHAMIDE
MAINTENANCE
RITUXIMAB

Access to Document

10.1056/NEJMoa1213277

Cite this

Specks, U., Merkel, P. A., Seo, P., Spiera, R., Langford, C. A., Hoffman, G. S., Kallenberg, C. G. M., Clair, E. W. S., Fessler, B. J., Ding, L., Viviano, L., Tchao, N. K., Phippard, D. J., Asare, A. L., Lim, N., Ikle, D., Jepson, B., Brunetta, P., Allen, N. B., ... RAVE-ITN Res Grp (2013). Efficacy of Remission-Induction Regimens for ANCA-Associated Vasculitis. New England Journal of Medicine, 369(5), 417-427. https://doi.org/10.1056/NEJMoa1213277

Specks, Ulrich ; Merkel, Peter A. ; Seo, Philip ; Spiera, Robert ; Langford, Carol A. ; Hoffman, Gary S. ; Kallenberg, Cees G. M. ; Clair, E. William St. ; Fessler, Barri J. ; Ding, Linna ; Viviano, Lisa ; Tchao, Nadia K. ; Phippard, Deborah J. ; Asare, Adam L. ; Lim, Noha ; Ikle, David ; Jepson, Brett ; Brunetta, Paul ; Allen, Nancy B. ; Fervenza, Fernando C. ; Geetha, Duvuru ; Keogh, Karina ; Kissin, Eugene Y. ; Monach, Paul A. ; Peikert, Tobias ; Stegeman, Coen ; Ytterberg, Steven R. ; Mueller, Mark ; Sejismundo, Lourdes P. ; Mieras, Kathleen ; Stone, John H. ; RAVE-ITN Res Grp. / Efficacy of Remission-Induction Regimens for ANCA-Associated Vasculitis. In: New England Journal of Medicine. 2013 ; Vol. 369, No. 5. pp. 417-427.

@article{1164481dd6184fb58c25359fcc714ae6,

title = "Efficacy of Remission-Induction Regimens for ANCA-Associated Vasculitis",

abstract = "BackgroundThe 18-month efficacy of a single course of rituximab as compared with conventional immunosuppression with cyclophosphamide followed by azathioprine in patients with severe (organ-threatening) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is unknown.MethodsIn a multicenter, randomized, double-blind, double-dummy, noninferiority trial, we compared rituximab (375 mg per square meter of body-surface area administered once a week for 4 weeks) followed by placebo with cyclophosphamide administered for 3 to 6 months followed by azathioprine for 12 to 15 months. The primary outcome measure was complete remission of disease by 6 months, with the remission maintained through 18 months.ResultsA total of 197 patients were enrolled. As reported previously, 64% of the patients in the rituximab group, as compared with 53% of the patients in the cyclophosphamide-azathioprine group, had a complete remission by 6 months. At 12 and 18 months, 48% and 39%, respectively, of the patients in the rituximab group had maintained the complete remissions, as compared with 39% and 33%, respectively, in the comparison group. Rituximab met the prespecified criteria for noninferiority (PConclusionsIn patients with severe ANCA-associated vasculitis, a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for the induction and maintenance of remissions over the course of 18 months. (Funded by the National Institute of Allergy and Infectious Diseases and others; RAVE ClinicalTrials.gov number, .)",

keywords = "ANTIBODY-ASSOCIATED VASCULITIS, ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES, WEGENERS-GRANULOMATOSIS, RANDOMIZED-TRIAL, SYSTEMIC VASCULITIDES, RENAL VASCULITIS, CELL-ACTIVATION, CYCLOPHOSPHAMIDE, MAINTENANCE, RITUXIMAB",

author = "Ulrich Specks and Merkel, {Peter A.} and Philip Seo and Robert Spiera and Langford, {Carol A.} and Hoffman, {Gary S.} and Kallenberg, {Cees G. M.} and Clair, {E. William St.} and Fessler, {Barri J.} and Linna Ding and Lisa Viviano and Tchao, {Nadia K.} and Phippard, {Deborah J.} and Asare, {Adam L.} and Noha Lim and David Ikle and Brett Jepson and Paul Brunetta and Allen, {Nancy B.} and Fervenza, {Fernando C.} and Duvuru Geetha and Karina Keogh and Kissin, {Eugene Y.} and Monach, {Paul A.} and Tobias Peikert and Coen Stegeman and Ytterberg, {Steven R.} and Mark Mueller and Sejismundo, {Lourdes P.} and Kathleen Mieras and Stone, {John H.} and {RAVE-ITN Res Grp}",

year = "2013",

month = aug,

day = "1",

doi = "10.1056/NEJMoa1213277",

language = "English",

volume = "369",

pages = "417--427",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "MASSACHUSETTS MEDICAL SOC",

number = "5",

}

Specks, U, Merkel, PA, Seo, P, Spiera, R, Langford, CA, Hoffman, GS, Kallenberg, CGM, Clair, EWS, Fessler, BJ, Ding, L, Viviano, L, Tchao, NK, Phippard, DJ, Asare, AL, Lim, N, Ikle, D, Jepson, B, Brunetta, P, Allen, NB, Fervenza, FC, Geetha, D, Keogh, K, Kissin, EY, Monach, PA, Peikert, T, Stegeman, C, Ytterberg, SR, Mueller, M, Sejismundo, LP, Mieras, K, Stone, JH & RAVE-ITN Res Grp 2013, 'Efficacy of Remission-Induction Regimens for ANCA-Associated Vasculitis', New England Journal of Medicine, vol. 369, no. 5, pp. 417-427. https://doi.org/10.1056/NEJMoa1213277

Efficacy of Remission-Induction Regimens for ANCA-Associated Vasculitis. / Specks, Ulrich; Merkel, Peter A.; Seo, Philip; Spiera, Robert; Langford, Carol A.; Hoffman, Gary S.; Kallenberg, Cees G. M.; Clair, E. William St.; Fessler, Barri J.; Ding, Linna; Viviano, Lisa; Tchao, Nadia K.; Phippard, Deborah J.; Asare, Adam L.; Lim, Noha; Ikle, David; Jepson, Brett; Brunetta, Paul; Allen, Nancy B.; Fervenza, Fernando C.; Geetha, Duvuru; Keogh, Karina; Kissin, Eugene Y.; Monach, Paul A.; Peikert, Tobias; Stegeman, Coen; Ytterberg, Steven R.; Mueller, Mark; Sejismundo, Lourdes P.; Mieras, Kathleen; Stone, John H.; RAVE-ITN Res Grp.

In: New England Journal of Medicine, Vol. 369, No. 5, 01.08.2013, p. 417-427.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Efficacy of Remission-Induction Regimens for ANCA-Associated Vasculitis

AU - Specks, Ulrich

AU - Merkel, Peter A.

AU - Seo, Philip

AU - Spiera, Robert

AU - Langford, Carol A.

AU - Hoffman, Gary S.

AU - Kallenberg, Cees G. M.

AU - Clair, E. William St.

AU - Fessler, Barri J.

AU - Ding, Linna

AU - Viviano, Lisa

AU - Tchao, Nadia K.

AU - Phippard, Deborah J.

AU - Asare, Adam L.

AU - Lim, Noha

AU - Ikle, David

AU - Jepson, Brett

AU - Brunetta, Paul

AU - Allen, Nancy B.

AU - Fervenza, Fernando C.

AU - Geetha, Duvuru

AU - Keogh, Karina

AU - Kissin, Eugene Y.

AU - Monach, Paul A.

AU - Peikert, Tobias

AU - Stegeman, Coen

AU - Ytterberg, Steven R.

AU - Mueller, Mark

AU - Sejismundo, Lourdes P.

AU - Mieras, Kathleen

AU - Stone, John H.

AU - RAVE-ITN Res Grp

PY - 2013/8/1

Y1 - 2013/8/1

N2 - BackgroundThe 18-month efficacy of a single course of rituximab as compared with conventional immunosuppression with cyclophosphamide followed by azathioprine in patients with severe (organ-threatening) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is unknown.MethodsIn a multicenter, randomized, double-blind, double-dummy, noninferiority trial, we compared rituximab (375 mg per square meter of body-surface area administered once a week for 4 weeks) followed by placebo with cyclophosphamide administered for 3 to 6 months followed by azathioprine for 12 to 15 months. The primary outcome measure was complete remission of disease by 6 months, with the remission maintained through 18 months.ResultsA total of 197 patients were enrolled. As reported previously, 64% of the patients in the rituximab group, as compared with 53% of the patients in the cyclophosphamide-azathioprine group, had a complete remission by 6 months. At 12 and 18 months, 48% and 39%, respectively, of the patients in the rituximab group had maintained the complete remissions, as compared with 39% and 33%, respectively, in the comparison group. Rituximab met the prespecified criteria for noninferiority (PConclusionsIn patients with severe ANCA-associated vasculitis, a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for the induction and maintenance of remissions over the course of 18 months. (Funded by the National Institute of Allergy and Infectious Diseases and others; RAVE ClinicalTrials.gov number, .)

AB - BackgroundThe 18-month efficacy of a single course of rituximab as compared with conventional immunosuppression with cyclophosphamide followed by azathioprine in patients with severe (organ-threatening) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is unknown.MethodsIn a multicenter, randomized, double-blind, double-dummy, noninferiority trial, we compared rituximab (375 mg per square meter of body-surface area administered once a week for 4 weeks) followed by placebo with cyclophosphamide administered for 3 to 6 months followed by azathioprine for 12 to 15 months. The primary outcome measure was complete remission of disease by 6 months, with the remission maintained through 18 months.ResultsA total of 197 patients were enrolled. As reported previously, 64% of the patients in the rituximab group, as compared with 53% of the patients in the cyclophosphamide-azathioprine group, had a complete remission by 6 months. At 12 and 18 months, 48% and 39%, respectively, of the patients in the rituximab group had maintained the complete remissions, as compared with 39% and 33%, respectively, in the comparison group. Rituximab met the prespecified criteria for noninferiority (PConclusionsIn patients with severe ANCA-associated vasculitis, a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for the induction and maintenance of remissions over the course of 18 months. (Funded by the National Institute of Allergy and Infectious Diseases and others; RAVE ClinicalTrials.gov number, .)

KW - ANTIBODY-ASSOCIATED VASCULITIS

KW - ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES

KW - WEGENERS-GRANULOMATOSIS

KW - RANDOMIZED-TRIAL

KW - SYSTEMIC VASCULITIDES

KW - RENAL VASCULITIS

KW - CELL-ACTIVATION

KW - CYCLOPHOSPHAMIDE

KW - MAINTENANCE

KW - RITUXIMAB

U2 - 10.1056/NEJMoa1213277

DO - 10.1056/NEJMoa1213277

M3 - Article

VL - 369

SP - 417

EP - 427

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 5

ER -