Multicentric study comparing cyclosporine, mycophenolate mofetil and azathioprine in the maintenance therapy of lupus nephritis: 8 years follow up

Background: The ideal long-term maintenance therapy of Lupus Nephritis (LN) is still a matter of debate. The present study was aimed at comparing the efficacy/safety profile of cyclosporine (CsA), mycophenolate mofetil (MMF) and azathioprine (AZA) in long-term maintenance therapy of LN. Methods: We performed a retrospective study of patients with biopsy-proven active LN. After induction therapy, all patients received maintenance therapy with CsA, MMF or AZA based on medical decision. Primary endpoint was complete renal remission (CRR) after 8 years (defined as proteinuria < 0.5 g/24 h, eGFR > 60 ml/min/1.73 mq); secondary endpoints were: CRR after 1 year, renal and extrarenal flares, progression of chronic kidney disease (CKD stage 3 or above) and side-effects. Results: Out of 106 patients, 34 received CsA, 36 MMF and 36 AZA. Clinical and histological characteristics at start of induction therapy were comparable among groups. At start of maintenance therapy, CsA patients had significantly higher proteinuria (P = 0.004) or nephrotic syndrome (P = 0.024) and significantly lower CRR (23.5% vs 55.5% on MMF and 41.7% on AZA, P = 0.024). At one year, CRR was similar in the three groups (79.4% on CsA, 63.8% on MMF, 58.3% on AZA, P = 0.2). At 8 years, the primary endpoint was achieved by 79.4% of CsA vs 83.3% of MMF and 77.8% of AZA patients (P = 0.83); 24 h proteinuria, serum creatinine, eGFR were similar. CKD stage 3 or above developed in 8.8% of CsA, in 8.3% of MMF and in 8.3% of AZA patients (P = 0.92). Flares-free survival curves and incidence of side-effects were not different. Conclusions: This is the first study comparing CsA, MMF and AZA on long-term LN maintenance therapy. All treatments had similar efficacy in achieving and maintaining CRR, despite more severe baseline clinical features in patients treated with CsA.