TY - JOUR
T1 - Mycophenolate Mofetil Versus Cyclophosphamide for the Induction of Remission in Nonlife-Threatening Relapses of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis
T2 - Randomized, Controlled Trial
AU - Tuin, Janneke
AU - Stassen, Patricia M.
AU - Bogdan, Daria I.
AU - Broekroelofs, Jan
AU - van Paassen, Pieter
AU - Tervaert, Jan Willem Cohen
AU - Sanders, Jan-Stephan
AU - Stegeman, Coen A.
N1 - Funding Information:
We thank Dr. P.L.A. van Daele, Dr. W.P. Haanstra, Dr. M.H. Hemmelder, Dr. K.W. Mui, Dr. R.R.H. Nap, and Dr. H.P.J. Willems for inclusion of participants in this trial. We thank Roche for providing study medication. Data of this trial can be shared at request. Our deidentified database will be available at request for fellow researchers from publication until June 2026 for 7 years. Data can only be shared within a secured data transfer system. We will not publish the database open access. The original study protocol is available for all who want to review it. Roche was not involved in analyzing, writing, reviewing, or approving the manuscript.
Publisher Copyright:
© 2019 by the American Society of Nephrology.
PY - 2019/7/5
Y1 - 2019/7/5
N2 - Background and objectivesCyclophosphamide has been the mainstay of treatment of ANCA-associated vasculitis. However, cyclophosphamide has unfavorable side effects and alternatives are needed. Evidence suggests that mycophenolate mofetil can induce sustained remission in nonlife-threatening disease. The purpose of this study was to compare the efficacy and safety of mycophenolate mofetil versus cyclophosphamide for the induction treatment of nonlife-threatening relapses of proteinase 3-ANCA- and myeloperoxidase-ANCA-associated vasculitis.Design, setting, participants, & measurementsWe conducted a multicenter randomized, controlled trial. Participants with a first or second relapse of ANCA-associated vasculitis were randomized to induction treatment with cyclophosphamide or mycophenolate mofetil both in combination with glucocorticoids. Maintenance therapy consisted of azathioprine in both arms. Primary outcome was remission at 6 months, and secondary outcomes included disease-free survival at 2 and 4 years.ResultsEighty-four participants were enrolled, of whom 41 received mycophenolate mofetil and 43 received cyclophosphamide. Eighty-nine percent of participants were proteinase 3-ANCA positive. At 6 months, 27 (66%) mycophenolate mofetil-treated participants versus 35 (81%) cyclophosphamide-treated participants were in remission (P=0.11). Disease-free survival rates at 2 and 4 years were 61% and 39% for cyclophosphamide, respectively, and 43% and 32% for mycophenolate mofetil, respectively (at 4 years, log rank test, P=0.17).ConclusionsWe did not demonstrate mycophenolate mofetil to be similarly effective as cyclophosphamide in inducing remission of relapsed ANCA-associated vasculitis. However, mycophenolate mofetil might be an alternative to cyclophosphamide for the treatment of selected patients with nonlife-threatening relapses.
AB - Background and objectivesCyclophosphamide has been the mainstay of treatment of ANCA-associated vasculitis. However, cyclophosphamide has unfavorable side effects and alternatives are needed. Evidence suggests that mycophenolate mofetil can induce sustained remission in nonlife-threatening disease. The purpose of this study was to compare the efficacy and safety of mycophenolate mofetil versus cyclophosphamide for the induction treatment of nonlife-threatening relapses of proteinase 3-ANCA- and myeloperoxidase-ANCA-associated vasculitis.Design, setting, participants, & measurementsWe conducted a multicenter randomized, controlled trial. Participants with a first or second relapse of ANCA-associated vasculitis were randomized to induction treatment with cyclophosphamide or mycophenolate mofetil both in combination with glucocorticoids. Maintenance therapy consisted of azathioprine in both arms. Primary outcome was remission at 6 months, and secondary outcomes included disease-free survival at 2 and 4 years.ResultsEighty-four participants were enrolled, of whom 41 received mycophenolate mofetil and 43 received cyclophosphamide. Eighty-nine percent of participants were proteinase 3-ANCA positive. At 6 months, 27 (66%) mycophenolate mofetil-treated participants versus 35 (81%) cyclophosphamide-treated participants were in remission (P=0.11). Disease-free survival rates at 2 and 4 years were 61% and 39% for cyclophosphamide, respectively, and 43% and 32% for mycophenolate mofetil, respectively (at 4 years, log rank test, P=0.17).ConclusionsWe did not demonstrate mycophenolate mofetil to be similarly effective as cyclophosphamide in inducing remission of relapsed ANCA-associated vasculitis. However, mycophenolate mofetil might be an alternative to cyclophosphamide for the treatment of selected patients with nonlife-threatening relapses.
KW - ANCA
KW - vasculitis
KW - mycophenolate mofetil
KW - cyclophosphamide
KW - randomized controlled trials
KW - relapse
KW - Mycophenolic Acid
KW - Antibodies
KW - Antineutrophil Cytoplasmic
KW - Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
KW - Recurrence
KW - Remission Induction
KW - THERAPY
U2 - 10.2215/CJN.11801018
DO - 10.2215/CJN.11801018
M3 - Article
C2 - 31253599
SN - 1555-9041
VL - 14
SP - 1021
EP - 1028
JO - Clinical journal of the American Society of Nephrology
JF - Clinical journal of the American Society of Nephrology
IS - 7
ER -