King's College London, Division of Immunology, Infection and Inflammatory Diseases, New Hunt's House, Guy's Campus, Great Maze Pond, London, SE1 1UL.
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'
Autoimmun Rev. 2016 Jan;15(1):93-101. doi: 10.1016/j.autrev.2015.09.006. Epub 2015 Sep 30.
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.
他克莫司在系统性红斑狼疮（SLE）治疗中的作用越来越受到关注。本系统评价和荟萃分析评估了他克莫司在狼疮肾炎治疗中的应用证据。通过 Cochrane 数据库、SCOPUS、Web of Science 和 OVID（MEDLINE 和 EMBASE），共确定了 13 项对照研究（9 项适合纳入）。使用 RevMan 软件提取和分析完全缓解率、部分缓解率、蛋白尿减少率和不良事件的数据。荟萃分析表明，与 IVCYC 相比，他克莫司总体上更能诱导完全肾脏缓解（p=0.004），但与 MMF 相比无显著差异（p=0.87）。仅当包括部分缓解时，多靶点 TAC+MMF 治疗才比 IVCYC 更有效（p=0.0006）。与其他用于狼疮肾炎治疗的药物相比，关键不良事件的发生率似乎相当，报告的胃肠道副作用、白细胞减少症、月经紊乱、感染和肝功能障碍发作较少，但新发高血压和高血糖较多。他克莫司组的死亡率较低，但无统计学意义（p=0.15）。他克莫司可能更有效地减少蛋白尿，但这也没有统计学意义。目前尚无关于在妊娠或青少年患者中使用的对照试验，但病例报告表明其具有潜在的疗效和安全性。总之，在中度严重的狼疮肾炎中，有一些证据支持他克莫司或多靶点 TAC+MMF 优于 IVCYC，但没有证据支持他克莫司优于 MMF。他克莫司可能更有效地减少蛋白尿，这可能对长期结局有影响。本研究的主要局限性是缺乏长期结局数据，以及缺乏多族裔人群的高质量、大型、双盲对照试验。
