The Effect of Mycophenolate Mofetil versus Cyclosporine as Combination Therapy with Low Dose Corticosteroids in High-risk Patients with Idiopathic Membranous Nephropathy: a Multicenter Randomized Trial

Abstract

BackgroundAppropriate immunosuppressive therapy for patients with idiopathic membranous nephropathy (MN) remains controversial. The effect of mycophenolate mofetil (MMF) versus cyclosporine (CsA) combined with low-dose corticosteroids was evaluated in patients with idiopathic MN in a multi-center randomized trial (NCT01282073).MethodsA total of 39 biopsy-proven idiopathic MN patients with severe proteinuria were randomly assigned to receive MMF combined with low-dose corticosteroids (MMF group) versus CsA combined with low-dose corticosteroids (CsA group), respectively, and followed up for 48 weeks. Complete or partial remission rate of proteinuria and estimated glomerular filtration rate (eGFR) at 48 weeks were compared.ResultsThe level of proteinuria at baseline and at 48 weeks was 8.9 ± 5.9 and 2.1 ± 3.1 g/day, respectively, in the MMF group compared to 8.4 ± 3.5 and 3.2 ± 5.7 g/day, respectively, in the CsA group. In total, 76.1% of the MMF group and 66.7% of the CsA group achieved remission at 48 weeks (95% confidence interval, −0.18 to 0.38). There was no difference in eGFR between the two groups. Anti-phospholipase A2 receptor Ab levels at baseline decreased at 48 weeks in the complete or partial remission group (P = 0.001), but were unchanged in the no-response group. There were no significant differences between the two groups in changes in the Gastrointestinal Symptom Rating Scale and Gastrointestinal Quality of Life Index scores from baseline to 48 weeks.ConclusionIn combination with low-dose corticosteroids, the effect of MMF may not be inferior to that of CsA in patients with idiopathic MN, with similar adverse effects including gastrointestinal symptoms.Trial RegistrationClinicalTrials.gov Identifier: NCT01282073

Comparative efficacy of 13 immunosuppressive agents for idiopathic membranous nephropathy in adults with nephrotic syndrome: a systematic review and network meta-analysis

“…A total of 1829 citations were retrieved based on electronic searches, and 12 additional studies were retrieved after checking the references of relevant reviews and guidelines. Ultimately, 48 studies21–68 including 2736 adults were available for network meta-analysis. These trials evaluated 13 different immunosuppressive treatment regimens, including ACTH, AZA, chlorambucil (CH), cyclophosphamide (CTX), cyclosporine (CsA), leflunomide (LEF), MMF, MZB, rituximab (RIT), steroids (STE), tacrolimus (TAC), tacrolimus+tripterygiumwilfordii (TAC+TW) and TW for patients with IMN.…”

“…TR (complete or PR) was reported in 2581 of the 2736 patients from a total of 45 studies 19–34 36–48 50–65. There were 13 immunosuppressive agents, including ACTH (1 trial, 16 patients), AZA (2, 18), CH (9, 268), CTX (21, 665), CsA (8, 167), LEF (2, 25), MMF (7, 139), MZB (1, 30), RIT (1, 37), STE (6, 179), TAC (15, 412), TAC+TW (2, 35) and TW (2, 93).…”

“…For the 24 hours UTP, 30 RCTs21 23 24 26–29 31 32 34 37–39 42 43 45 47 48 51 52 56–60 63–67 with 1682 patients were included in the network meta-analysis. There were 11 immunosuppressive agents, including AZA (2 trials, 18 patients), CH (4, 112), CTX (16, 487), CsA (6, 78), LEF (2, 25), MMF (3, 85), MZB (1, 30), RIT (1, 37), STE (4, 122), TAC (10, 257) and TAC+TW (2, 35).…”

<p>Efficacy and safety of cyclosporine A in the treatment of idiopathic membranous nephropathy in an Asian population</p>

“…Sixteen studies17–23,25–30,32–34 reported effects of CsA plus glucocorticoid (GC) vs CTX plus GC. Three studies24,31,35 reported comparisons among CsA plus GC, CTX plus GC, and mycophenolate mofetil (MMF) plus GC. Three studies36–38 compared tacrolimus (TAC) with the CsA.…”

“…Three studies24,31,35 assessed the CR rate of CsA+GC vs MMF+GC. The CsA group had similar efficacy to the MMF group (OR=0.92,95%CI: 0.41–2.05, P =0.83; Table 2).…”