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[免疫抑制剂和免疫调节剂治疗药物监测在自身免疫性疾病管理中的益处]

[Benefit of therapeutic drug monitoring of immunosuppressants and immunomodulators in the management of autoimmune diseases].

作者信息

Djabarouti S, Mora P, Lahouati M, Gigan M, d'Houdain N, Sourisseau B, Chambord J, Xuereb F

机构信息

CHU de Bordeaux, pôle produits de santé, service pharmacie à usage intérieur, 33600 Pessac, France; Université de Bordeaux, Inserm, biologie des maladies cardiovasculaires, U1034, 33600 Pessac, France.

CHU de Bordeaux, pôle produits de santé, service pharmacie à usage intérieur, 33600 Pessac, France; Université de Bordeaux, Inserm, biologie des maladies cardiovasculaires, U1034, 33600 Pessac, France.

出版信息

Rev Med Interne. 2022 Jul;43(7):412-418. doi: 10.1016/j.revmed.2022.03.343. Epub 2022 May 25.

Abstract

The pharmacokinetics of drugs, such as immunosuppressants, justify the need of measuring their blood concentrations in order to adjust their dosage. Therapeutic Drug Monitoring (TDM) of ciclosporin, tacrolimus and mycophenolate mofetil has shown its benefit particularly in the management of renal transplantees, in order to prevent graft rejection. When prescribed in autoimmune diseases, their pharmacokinetic variability and the variability of clinical response would justify TDM in practice. TDM may be useful in systemic lupus, for hydroxychloroquine, in order to monitor patient compliance. Despite insufficient data in the literature, for mycophenolate mofetil, TDM would permit to maintain clinical remission in adults and children with lupus nephritis, as well as in mucosal pemphigoid and idiopathic nephrotic syndrome in children. Studies are still necessary to validate the thresholds and TDM conditions. For azathioprine, TPMT phenotyping is recommended before prescription. For methotrexate, tacrolimus and ciclosporin, data are still sparse on the benefit of TDM, although it may improve tolerance to tacrolimus in lupus. Finally, for infliximab, in case of loss of response in maintenance, TDM may be proposed in parallel with detection of anti-drug antibodies.

摘要

免疫抑制剂等药物的药代动力学情况表明,有必要检测其血药浓度以调整用药剂量。环孢素、他克莫司和吗替麦考酚酯的治疗药物监测(TDM)已显示出其益处,尤其在肾移植受者的管理中,可预防移植排斥反应。在自身免疫性疾病中开具这些药物时,其药代动力学变异性和临床反应变异性在实际应用中证明了TDM的合理性。TDM对于系统性红斑狼疮患者使用羟氯喹来说可能有用,以便监测患者的依从性。尽管文献数据不足,但对于吗替麦考酚酯,TDM有助于维持狼疮性肾炎成人和儿童患者以及儿童黏膜类天疱疮和特发性肾病综合征患者的临床缓解。仍需开展研究以验证TDM的阈值和条件。对于硫唑嘌呤,建议在处方前进行硫嘌呤甲基转移酶(TPMT)基因分型。对于甲氨蝶呤、他克莫司和环孢素,关于TDM益处的数据仍然稀少,尽管TDM可能改善狼疮患者对他克莫司的耐受性。最后,对于英夫利昔单抗,在维持治疗中出现反应丧失的情况下,可在检测抗药物抗体的同时进行TDM。

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