Mycophenolate mofetil (MMF) reduces the risk of disease progression in patients with immunoglobulin A nephropathy (IgAN), a new study finds.
In The Effect of Mycophenolate Mofetil on Renal Outcomes in Advanced Immunoglobulin A Nephropathy (MAIN) randomized clinical trial of 170 patients with IgAN (ClinicalTrials.gov Identifier: NCT01854814), adding MMF to supportive care significantly reduced the risk of a composite outcome by 77% compared with supportive care alone, Fan Fan Hou, MD, PhD, of Nanfang Hospital, Southern Medical University in Guangzhou, China, and colleagues reported in JAMA Network Open. The composite endpoint included creatinine doubling, indication for kidney replacement therapy, or death due to a kidney or cardiovascular cause. The composite outcome occurred in 7.1% of the MMF group compared with 21.2% of the usual care group.
The addition of MMF also significantly reduced the risk of chronic kidney disease (CKD) progression by 77%, the investigators reported. CKD progression occurred in 8.2% of the MMF group compared with 27.1% of the usual care group. Progression was defined as a decline in estimated glomerular filtration rate (eGFR) of 30% or more when baseline eGFR was 60 mL/min/1.73 m2 or higher or 50% of more when eGFR was less than 60 mL/min/1.73 m2.
Once MMF was discontinued, kidney function declined faster. Annual eGFR decline was a mean 2.9 mL/min/1.73 m2 during MMF treatment compared with 6.1 mL/min/1.73 m2 after discontinuation.
Up to 40% of patients with IgAN progress to end-stage kidney disease over 10 to 20 years. Immune and autoimmune activation in IgAN suggests a potential benefit of immunosuppression for treating the disease, Dr Hou’s team noted. Their findings are consistent with results from the TESTING trial, but differ from results from the observational STOP-IgAN study.
“Mycophenolate mofetil (MMF) is a potent immunosuppressive agent that is relatively selective for lymphocytes and inhibits antibody production by B cells more strongly than any other immunosuppressant,” Dr Hou’s team stated.
“These results suggest that the addition of MMF to optimized [supportive care] was superior to [supportive care] alone in improving kidney outcomes and may be an alternative therapy for patients with IgAN, particularly those with CKD and subnephrotic proteinuria despite receiving [supportive care], as well as those not appropriate for steroid therapy.”
Serious adverse events were not more frequent with MMF compared with usual care. Infection, particularly pneumonia, and gastrointestinal symptoms, such as abdominal distension and diarrhea, were more common in the MMF group.
At baseline, patients had a urinary protein excretion rate greater than 1 g/d and an eGFR of 30-60 mL/min/1.73 m2 or persistent hypertension. During a 12-week run-in period, all patients received supportive care, including optimal inhibition of the renin-angiotensin system with losartan, blood pressure control, lifestyle modification, and statins as needed. After the run-in phase, investigators randomly assigned 170 patients with persistent proteinuria of 0.75 to 3.5 g/d to receive MMF plus supportive care or supportive care alone. The MMF group received 1.5 g/d oral MMF for 12 months, tapered to 0.75 to 1.0 g/d for at least 6 months.
Major exclusion criteria for the trial included secondary, familial, crescentic IgAN, other types of CKD, prior immunosuppressive therapy, baseline eGFR less than 30 mL/min/1.73 m2, and proteinuria greater than 3.5 g/d.
Disclosure: This study drug was provided by Hangzhou Zhongmei Huadong Pharmaceutical Co, Ltd. Please see the original reference for a full list of disclosures.
Hou FF, Xie D, Wang J, et al; MAIN Trial Investigators. Effectiveness of mycophenolate mofetil among patients with progressive IgA nephropathy: A randomized clinical trial. JAMA Netw Open. Published online February 1, 2023. doi:10.1001/jamanetworkopen.2022.54054