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  • Title: Calcineurin inhibitors in systemic lupus erythematosus.
    Author: Mok CC.
    Journal: Best Pract Res Clin Rheumatol; 2017 Jun; 31(3):429-438. PubMed ID: 29224682.
    Abstract:
    The calcineurin inhibitors (CNIs) belong to a group of immunosuppressive agents that block T-cell activation through the suppression of the calcium/calcimodulin-dependent phosphatase calcineurin. Agents such as cyclosporine A (CSA) and tacrolimus (TAC) have long been used in patients with systemic lupus erythematosus (SLE). TAC is preferred to CSA in SLE because of the lower frequency of cosmetic, hypertensive and dyslipidemic adverse effects. Recent randomised controlled trials have demonstrated noninferiority of TAC to mycophenolate mofetil (MMF) or cyclophosphamide (CYC) for induction therapy of lupus nephritis. Low-dose combination of TAC and MMF has also been shown to outperform CYC pulses in inducing remission of lupus nephritis in Chinese patients. TAC does not affect fertility and is relatively safe in pregnancy. In SLE patients who are intolerant or refractory to conventional immunosuppressives, or where contraindications to other immunosuppressive agents exist, TAC is an alternative option. However, the therapeutic window of TAC is narrow, and drug level monitoring is required to ensure drug exposure and minimise toxicities. Current evidence of TAC in lupus nephritis is limited to 6 months, and its long-term safety as maintenance therapy of SLE is yet to be determined. Newer chemical analogues of CNIs, such as voclosporin, with less variable plasma concentration are being tested in lupus nephritis.
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