Con: The use of calcineurin inhibitors in the treatment of lupus nephritis

Abstract

Lupus nephritis (LN) therapy has limited efficacy due to its toxicity, and LN patients suffer high risks of renal and cardiovascular morbidity and mortality. Calcineurin inhibitors (CNIs) have been used for over >30 years in LN treatment and are an established alternative therapy for Class V nephritis, but uncertainty remains about their role in proliferative disease or in the maintenance of remission. More recently, the combination of CNIs with mycophenolate mofetil (MMF) and glucocorticoid combination therapy, 'multitarget' therapy and the use of tacrolimus as opposed to ciclosporin has received attention. Is the evidence now sufficient to support the routine use of regimens including CNIs in LN? Although CNIs appear to have similar efficacy to MMF-based regimens as induction therapy, and are comparable with azathioprine as maintenance treatment, CNI toxicities, such as new-onset hypertension, hyperglycaemia and nephrotoxicity, have been problematic. Multitarget therapy improves the rate of complete remission in short-term studies, but whether this benefit is maintained over the longer term is uncertain. However, patient tolerability is lower and the frequency of serious events is higher in multitarget versus cyclophosphamide-based regimens, and there is a paucity of evidence from non-Asian ethnic groups. CNI-based therapy is also complicated by the absence of standardized dosing and the need for drug level monitoring, as well as by pharmacogenetic differences. Also, multitarget therapy increases the complexity and the cost of treatment. There is insufficient evidence to support the routine use of CNI-based or multitarget therapy for proliferative LN. Further data on long-term renal and cardiovascular outcomes and strategies to improve tolerability and safety are required.