Long-term follow-up of the MAINTAIN Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis

Abstract

Objective: To report the 10-year follow-up of the MAINTAIN Nephritis Trial comparing azathioprine (AZA) and mycophenolate mofetil (MMF) as maintenance therapy of proliferative lupus nephritis, and to test different definitions of early response as predictors of long-term renal outcome.

Methods: In 2014, data on survival, kidney function, 24 h proteinuria, renal flares and other outcomes were collected for the 105 patients randomised between 2002 and 2006, except in 13 lost to follow-up.

Results: Death (2 and 3 in the AZA and MMF groups, respectively) and end-stage renal disease (1 and 3, respectively) were rare events. Time to renal flare (22 and 19 flares in AZA and MMF groups, respectively) did not differ between AZA and MMF patients. Patients with good long-term renal outcome had a much more stringent early decrease of 24 h proteinuria compared with patients with poor outcome. The positive predictive value of a 24 h proteinuria <0.5 g/day at 3 months, 6 months and 12 months for a good long-term renal outcome was excellent (between 89% and 92%). Inclusion of renal function and urinalysis in the early response criteria did not impact the value of early proteinuria decrease as long-term prognostic marker.

Conclusions: The long-term follow-up data of the MAINTAIN Nephritis Trial do not indicate that MMF is superior to AZA as maintenance therapy in a Caucasian population suffering from proliferative lupus nephritis. Moreover, we confirm the excellent positive predictive value of an early proteinuria decrease for long-term renal outcome.

Trial registration number: NCT00204022.

Keywords: Lupus Nephritis; Outcomes research; Treatment.

Figure 1

Kaplan–Meier analysis of the probability of an absence of end-stage renal disease (ESRD) (A), all types of renal flare (B), proteinuric flare (C) and nephritic flare (D). All patients received Euro-Lupus intravenous cyclophosphamide, followed by azathioprine (AZA) or mycophenolate mofetil (MMF) as maintenance therapy. Survival curves were statistically tested with the logrank test. HR (95% CI). Numbers shown in abscissa are the number of patients at risk in each group at each time point. Analysis was by intention-to-treat.

Figure 2

Differential kinetics of 24 h proteinuria decrease in patients with a good and poor long-term renal outcome. Data are shown at baseline and after 3 months, 6 months and 12 months of treatment for patients with good long-term renal outcome (serum creatinine ≤120% of baseline value; n=83) or poor long-term renal outcome (serum creatinine >120% of baseline value; n=21). p Values indicated above the columns were calculated by Mann-Whitney tests.