title: Tacrolimus use in lupus nephritis: A systematic review and meta-analysis.
abstract: There is growing interest in the role of tacrolimus as a potential therapeutic agent in SLE. This systematic review and meta-analysis evaluates the evidence for tacrolimus use in the management of lupus nephritis. Thirteen controlled studies were identified (9 suitable for inclusion), using Cochrane database, SCOPUS, Web of Science and OVID (MEDLINE and EMBASE). Data on complete and partial remission rates, proteinuria reduction and adverse events was extracted and analysed using RevMan software. The meta-analysis showed that overall tacrolimus is more effective at inducing complete renal remission than IVCYC (p=0.004), but there is no significant difference compared to MMF (p=0.87). Multi-target TAC+MMF therapy is more effective than IVCYC only when partial remission is included (p=0.0006). Frequency of key adverse effects seems comparable to other agents used in the management of lupus nephritis with fewer gastrointestinal side effects, leukopenia, menstrual disorders, infections and episodes of liver dysfunction reported, but more new onset hypertension and hyperglycaemia. Mortality was lower in the tacrolimus groups, but this was not statistically significant (p=0.15). Tacrolimus may be more effective at reducing proteinuria, but again this was not statistically significant. There are no controlled trials looking at use in pregnancy or juvenile patients, however case reports suggest potential efficacy and safety. In conclusion, in moderately severe lupus nephritis, there is some evidence supporting efficacy of tacrolimus or multi-target TAC+MMF over IVCYC, but no evidence supporting tacrolimus over MMF. Tacrolimus may be more effective at reducing proteinuria, having potential implications for long-term outcome. Key limitations of this study are the lack of long-term outcome data and the lack of high quality, large, blinded controlled trials in multi-ethnic groups.
authors.affiliation: King's College London, Division of Immunology, Infection and Inflammatory Diseases, New Hunt's House, Guy's Campus, Great Maze Pond, London, SE1 1UL. Electronic address: jennifer.hannah1@nhs.net.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hannah
authors.affiliation: King's College London, Division of Immunology, Infection and Inflammatory Diseases, New Hunt's House, Guy's Campus, Great Maze Pond, London, SE1 1UL. Electronic address: alina.casian@doctors.org.uk.
authors.forename: Alina
authors.initials: A
authors.lastname: Casian
authors.affiliation: King's College London, Division of Immunology, Infection and Inflammatory Diseases, New Hunt's House, Guy's Campus, Great Maze Pond, London, SE1 1UL. Electronic address: david.d'cruz@kcl.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: D'Cruz
mesh_terms: D000818:Animals; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008181:Lupus Nephritis / Q000188:drug therapy*; D011507:Proteinuria; D012074:Remission Induction; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: Calcineurin inhibitor; Cyclophosphamide; Lupus nephritis; Proteinuria; Systemic lupus erythematosus; Tacrolimus