Induction therapy for membranous lupus nephritis: a
systematic review and network meta-analysis
and Der-Yuan CHEN
Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung,
Division of Pulmonary
Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei,
Institute of Epidemiology and
Preventive Medicine, National Taiwan University, Taipei,
Translational Medicine Laboratory, Rheumatic Diseases Research Center,
China Medical University Hospital, Taichung,
Rheumatology and Immunology Center, China Medical University Hospital,
School of Medicine, China Medical University, Taichung, Taiwan
Aim: Membranous lupus glomerulonephritis (MLN) is associated with morbidities such as thromboembolism,
peripheral edema and/or hyperlipidemia. However, treatment of MLN remains elusive.
Methods: We performed systematic searches on MEDLINE, EMBASE and Cochrane Library database up to
November, 2017. Eligible studies included randomized trials or cohort studies which evaluated different
immunosuppressants in adult patients with pathologically proved MLN. No language restrictions were applied.
Endpoints included complete remission (CR) as the primary outcome, and CR plus partial remission (PR) and
proteinuria-reducing effect as secondary outcomes. Frequentist estimation of a network meta-analysis (NMA)
random-effect model was performed.
Results: Eight studies (206 patients) were included with a total of six immunosuppressants as an induction
therapy for MLN. NMA results showed that both mycophenolate mofetil (MMF) and calcineurin inhibitors
(CNI) are effective in the induction of CR and CR plus PR when compared with corticosteroids (CS) alone, but
MMF and CNI are also associated with higher infection rates when compared with CS.
Conclusion: Our NMA demonstrated that both MMF and CNI are more effective than CS for induction therapy
in MLN patients. However, there are limitations due to intra- and inter-study variability.
Key words: lupus nephritis, mycophenolic acid, systemic lupus erythematosus, tacrolimus.
Renal disease, as a manifestation of systemic lupus
erythematosus (SLE), is a major cause of morbidity
Membranous lupus glomerulon-
ephritis (MLN) comprises 10–15% of lupus nephritis
Unlike proliferative lupus glomerulonephritis
(PLN), MLN is associated with a low risk of progres-
sion to end-stage renal disease, but carries a high risk
of thromboembolic complications.
In addition, MLN
is often associated with nephrotic-range proteinuria,
which leads to complications such as peripheral
edema, infection and/or hyperlipidemia.
most of the therapeutic trials have focused on the
management of PLN, whereas treatment of MLN
Mycophenolate mofetil (MMF) has
been recommended as the initial treatment for MLN
in both the European League Against Rheumatism
(EULAR) and the American College of Rheumatology
These recommendations are
based on a post hoc subgroup analysis of two random-
ized controlled trials (RCTs) of patients with lupus
However, recent studies have demonstrated
that newer therapies such as tacrolimus (TAC) are
Correspondence: Professor Der-Yuan Chen, Translational Medi-
cine Laboratory, Rheumatic Diseases Research Center, China
Medical University Hospital, No. 2, Yude Road, Taichung
40447, Taiwan. Email: firstname.lastname@example.org
KT Tang and CH Tseng contributed equally to this study.
© 2018 Asia Paciﬁc League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd
International Journal of Rheumatic Diseases 2018; 21: 1163–1172