Mycophenolate Mofetil Reduces Progression of IgAN

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In patients with high risk of immunoglobulin A nephropathy (IgAN), adding mycophenolate mofetil (MMF) to standard care reduces the risk of disease progression, concludes a randomized trial in JAMA Network Open.

The open-label Effect of Mycophenolate Mofetil on Renal Outcomes in Advanced Immunoglobulin A Nephropathy (MAIN) study enrolled 238 adult patients with IgAN at high risk of kidney function loss. Patients underwent a 3-month run-in period of optimized supportive care (SC), including losartan. Those who did not achieve a urinary protein excretion rate of 0.75 g/day or greater were randomly assigned to 3 years of treatment with MMF added to SC or to SC only. The initial MMF dose was 1.5 g/day for 12 months, maintained at 0.75–1.0 g.

Of 170 randomized patients, 55.3% were men; the mean age was 36.6 years. The mean estimated glomerular filtration rate (eGFR) was 50.1 mL/min/1.73 m2, and the proteinuria level was 1.9 g/day. The analysis focused on two co-primary outcomes: a composite of doubling of serum creatinine, end stage kidney disease, or death due to kidney or cardiovascular disease and progression of chronic kidney disease (CKD).

Of 168 patients who completed the trial, 157 were alive and free of dialysis or transplantation. A primary composite outcome event occurred in 7.1% in the MMF group versus 21.2% with SC only. Rates of CKD progression were 8.2% and 27.1%, respectively; for both outcomes, the adjusted hazard ratio was 0.23.

The benefits of MMF were apparent across subgroups. After the end of the study and withdrawal of MMF in 66 patients, annual loss of eGFR increased from 2.9 to 6.1 mL/min/1.73 m2. Adverse events were similar between treatment groups.

There are conflicting data on the effectiveness of immunosuppressive therapy for IgAN. MMF is relatively lymphocyte selective compared with other immunosuppressive agents and is a stronger inhibitor of B cell antibody production.

Adding MMF to SC can reduce disease progression in high-risk patients with IgAN, the MAIN results suggest. The researchers conclude that MMF “may be an alternative therapy for patients with IgAN, particularly those with CKD and subnephrotic proteinuria despite receiving SC, as well as those not appropriate for steroid therapy” [Hou FF, et al. Effectiveness of mycophenolate mofetil among patients with progressive IgA nephropathy: A randomized clinical trial. JAMA Network Open 2023; 6:e22254054; doi: 10.1001/jamanetworkopen.2022.54054].