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Randomized Controlled Trial
. 2023 Feb 1;6(2):e2254054.
doi: 10.1001/jamanetworkopen.2022.54054.

Effectiveness of Mycophenolate Mofetil Among Patients With Progressive IgA Nephropathy: A Randomized Clinical Trial

Fan Fan Hou  1   2   3   4   5 , Di Xie  1   2   3   4   5 , Jun Wang  1   2   3   4   5 , Xin Xu  1   2   3   4   5 , Xiaobing Yang  1   2   3   4   5 , Jun Ai  1   2   3   4   5 , Sheng Nie  1   2   3   4   5 , Min Liang  1   2   3   4   5 , Guobao Wang  1   2   3   4   5 , Nan Jia  1   2   3   4   5 ; MAIN Trial Investigators
Collaborators, Affiliations
Randomized Controlled Trial

Effectiveness of Mycophenolate Mofetil Among Patients With Progressive IgA Nephropathy: A Randomized Clinical Trial

Fan Fan Hou et al. JAMA Netw Open. .

Abstract

Importance: The role of mycophenolate mofetil (MMF) in management of immunoglobulin A nephropathy (IgAN) remains highly controversial.

Objective: To evaluate the efficacy and safety of MMF in patients with IgAN at high risk of kidney function loss.

Design, setting, and participants: This randomized clinical trial with open-label, blinded end-point design was conducted among adults with IgAN, proteinuria greater than 1.0 g/d, and estimated glomerular filtration rate (eGFR) greater than 30 and less than 60 mL/min/1.73m2 or with persistent hypertension from September 2013 to December 2015. During a 3-month run-in period, 238 patients received optimized supportive care (SC), including losartan. Patients with a urinary protein excretion rate of 0.75 g/d or greater despite of 3 months optimized SC were enrolled into the trial for 3 years. Survivors of the trial who did not receive dialysis or transplant were followed up after the trial for a median (IQR) of 60 (47-76) months. Data were analyzed from March through June 2022.

Interventions: A total of 170 participants were randomized in a 1:1 ratio to receive MMF (initially, 1.5 g/d for 12 months, maintained at 0.75-1.0 g for at least 6 months) plus SC or SC alone.

Main outcomes and measures: The primary outcomes were (1) a composite of doubling of serum creatinine, end-stage kidney disease (dialysis, transplant, or kidney failure without receiving kidney replacement therapy), or death due to kidney or cardiovascular cause and (2) progression of chronic kidney disease.

Results: Among 170 randomized patients (mean [SD] age 36.6 [9.4] years; 94 [55.3%] male patients), 85 patients received MMF with SC and 85 patients received SC alone. The mean (SD) eGFR was 50.1 (17.9) mL/min/1.73m2 and mean (SD) proteinuria level was 1.9 (1.7) g/d; 168 patients (98.8%) completed the trial, and 157 participants (92.4%) survived and did not receive dialysis or transplant. Primary composite outcome events occurred in 6 patients (7.1%) in the MMF group and 18 patients (21.2%) in the SC group (adjusted hazard ratio [aHR], 0.23; 95% CI, 0.09-0.63). Progression of chronic kidney disease occurred in 7 participants (8.2%) in the MMF group and 23 participants (27.1%) in the SC group (aHR, 0.23; 95% CI, 0.10-0.57). The effect of MMF treatment on primary outcomes was consistent across prespecified subgroups, with no significant interaction per subgroup. During posttrial follow-up, annual loss of eGFR accelerated after discontinuation of MMF; mean (SD) annual eGFR loss during the study period was 2.9 (1.0) mL/min/1.73m2 in the MMF group and 6.1 (1.2) mL/min/1.73m2 among 66 patients in the MMF group who discontinued MMF after the trial. Serious adverse events were not more frequent with MMF vs SC alone.

Conclusions and relevance: This study found that addition of MMF to SC compared with SC alone significantly reduced risk of disease progression among patients with progressive IgAN.

Trial registration: ClinicalTrials.gov Identifier: NCT01854814.

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Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.
Figure 1.. Study Flowchart
IgAN indicates immunoglobulin A nephropathy; MI, myocardial infarction; MMF, mycophenolate mofetil; SC, supportive care; UPER, urinary protein excretion rate.
Figure 2.
Figure 2.. Primary and Secondary Outcomes
A, Primary composite outcomes of Kaplan-Meier estimates of the percentage of patients free of the primary composite end point of a doubling of serum creatinine levels, end-stage kidney disease, or death due to kidney or cardiovascular cause are presented. B, Primary outcomes of Kaplan-Meier estimates of the percentage of patients without disease progression are presented. C, Secondary outcomes of Kaplan-Meier estimates of the percentage of patients without an estimated glomerular filtration rate (eGFR) decline of more than 30% of baseline are presented. D, Secondary outcomes of a change in urinary protein excretion rate (UPER; percentage of baseline) are presented. Horizontal line indicates reduction in proteinuria from baseline; MMF, mycophenolate mofetil; SC, supportive care.
Figure 3.
Figure 3.. Primary Outcomes by Prespecified Subgroup at Baseline
A, The forest plot of hazard ratios (HRs) for the primary composite outcome are shown. B, The forest plot of HRs for progression of chronic kidney disease are shown. eGFR indicates estimated glomerular filtration rate; MMF, mycophenolate mofetil; SC, supportive care.
See this image and copyright information in PMC

References

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