TY - JOUR
T1 - Mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA-associated vasculitis
T2 - a randomised, non-inferiority trial
AU - European Vasculitis Study Group (EUVAS)
AU - Jones, Rachel B.
AU - Hiemstra, Thomas F
AU - Ballarin, Jose
AU - Engelbert Blockmans, Daniel
AU - Brogan, Paul
AU - Bruchfeld, Annette
AU - Cid, Maria C.
AU - Dahlsveen, Karen
AU - de Zoysa, Janak
AU - Espigol-Frigolé, Georgína
AU - Lanyon, Peter
AU - Peh, Chen Au
AU - Tesar, Vladimir
AU - Vaglio, Augusto
AU - Walsh, Michael
AU - Walsh, Dorothy
AU - Walters, Giles
AU - Harper, Lorraine
AU - Jayne, David
PY - 2019/3
Y1 - 2019/3
N2 - Objectives
Cyclophosphamide
induction regimens are effective for antineutrophil cytoplasmic antibody
(ANCA)- associated vasculitis (AAV), but are associated with infections,
malignancies and infertility. Mycophenolate mofetil (MMF) has shown high
remission rates in small studies of AAV.
Methods
We conducted
a randomised controlled trial to investigate whether MMF was non-inferior to
cyclophosphamide for remission induction in AAV. 140 newly diagnosed patients
were randomly assigned to MMF or pulsed cyclophosphamide. All patients received
the same oral glucocorticoid regimen and were switched to azathioprine
following remission. The primary endpoint was remission by 6 months requiring
compliance with the tapering glucocorticoid regimen. Patients with an eGFR
<15 mL/min were excluded from the study.
Results
At baseline,
ANCA subtype, disease activity and organ involvement were similar between
groups. Non-inferiority was demonstrated for the primary remission endpoint,
which occurred in 47 patients (67%) in the MMF group and 43 patients (61%) in
the cyclophosphamide group (risk difference 5.7%, 90%CI −7.5% to 19%).
Following remission, more relapses occurred in the MMF group (23 patients, 33%)
compared with the cyclophosphamide group (13 patients, 19%) (incidence rate
ratio 1.97, 95%CI 0.96 to 4.23, p=0.049). In MPO-ANCA patients, relapses
occurred in 12% of the cyclophosphamide group and 15% of the MMF group. In
PR3-ANCA patients, relapses occurred in 24% of the cyclophosphamide group and
48% of the MMF group. Serious infections were similar between groups (26% MMF
group, 17% cyclophosphamide group) (OR 1.67, 95% CI 0.68 to 4.19, p=0.3).
Conclusion
MMF was
non-inferior to cyclophosphamide for remission induction in AAV, but resulted
in higher relapse rate.
Trial
registration number
NCT00414128
AB - Objectives
Cyclophosphamide
induction regimens are effective for antineutrophil cytoplasmic antibody
(ANCA)- associated vasculitis (AAV), but are associated with infections,
malignancies and infertility. Mycophenolate mofetil (MMF) has shown high
remission rates in small studies of AAV.
Methods
We conducted
a randomised controlled trial to investigate whether MMF was non-inferior to
cyclophosphamide for remission induction in AAV. 140 newly diagnosed patients
were randomly assigned to MMF or pulsed cyclophosphamide. All patients received
the same oral glucocorticoid regimen and were switched to azathioprine
following remission. The primary endpoint was remission by 6 months requiring
compliance with the tapering glucocorticoid regimen. Patients with an eGFR
<15 mL/min were excluded from the study.
Results
At baseline,
ANCA subtype, disease activity and organ involvement were similar between
groups. Non-inferiority was demonstrated for the primary remission endpoint,
which occurred in 47 patients (67%) in the MMF group and 43 patients (61%) in
the cyclophosphamide group (risk difference 5.7%, 90%CI −7.5% to 19%).
Following remission, more relapses occurred in the MMF group (23 patients, 33%)
compared with the cyclophosphamide group (13 patients, 19%) (incidence rate
ratio 1.97, 95%CI 0.96 to 4.23, p=0.049). In MPO-ANCA patients, relapses
occurred in 12% of the cyclophosphamide group and 15% of the MMF group. In
PR3-ANCA patients, relapses occurred in 24% of the cyclophosphamide group and
48% of the MMF group. Serious infections were similar between groups (26% MMF
group, 17% cyclophosphamide group) (OR 1.67, 95% CI 0.68 to 4.19, p=0.3).
Conclusion
MMF was
non-inferior to cyclophosphamide for remission induction in AAV, but resulted
in higher relapse rate.
Trial
registration number
NCT00414128
KW - ANCA-associated vasculitis
KW - cyclophosphamide
KW - induction therapy
KW - mycophenolate
KW - randomised trial
UR - http://www.scopus.com/inward/record.url?scp=85059759941&partnerID=8YFLogxK
U2 - 10.1136/annrheumdis-2018-214245
DO - 10.1136/annrheumdis-2018-214245
M3 - Article
SN - 0003-4967
VL - 78
SP - 399
EP - 405
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
IS - 3
ER -