Kagawa Hidetoshi, Hiromasa Tsutomu, Yamanaka Ryutaro, Hayashi Reika, Tsunashima Yoko, Inoue Tatsuyuki, Sada Ken-Ei
Department of Internal Medicine, Japanese Red Cross Himeji Hospital, 1-12-1 Shimoteno, Himeji, 670-8540, Japan.
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Clin Exp Nephrol. 2018 Dec;22(6):1371-1378. doi: 10.1007/s10157-018-1597-8. Epub 2018 Jun 9.
Despite the high efficacy of mycophenolate mofetil (MMF)/tacrolimus-based multitarget treatment, risks of infections are a matter of concern. In the present study, we clarified the potential of multitarget therapy using mizoribine opposed to MMF.
A total of 36 patients with biopsy-proven lupus nephritis were treated with mizoribine, tacrolimus, and glucocorticoids and then retrospectively evaluated. To determine the efficacy, proteinuria remission (≤ 0.2 g/day), complete remission (Liu et al. in Ann Intern Med 162:18-26, 2015) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) remission rates, and the prednisolone dose at months 6 and 12 were evaluated. The associations between serum mizoribine/tacrolimus levels and clinical parameters were investigated. To assess safety, adverse events were inspected.
All patients could continue the original treatment regimen without withdrawal or exacerbations through month 12. At month 6, the proteinuria remission, complete remission, SLEDAI remission rates, and prednisolone dose were 69, 53, 36%, and 12.1 mg/day, respectively, whereas the values at 12 months were 92, 67, 50%, and 8.8 mg/day, respectively. The treatment was efficacious for every histologic type of nephritis and non-renal manifestations of SLE. Excluding one patient who was hospitalized due to upper respiratory tract infection, serious infections, including pneumonia and cytomegalovirus disease, were not observed. Higher trough tacrolimus levels were associated with normalization of complement, whereas higher peak mizoribine levels with prevention of cytomegalovirus viremia.
Our results suggest that multitarget therapy using mizoribine opposed to MMF is highly safe and effective through 12 months. The therapy may enable faster dose reduction of concomitant glucocorticoids.
尽管霉酚酸酯（MMF）/他克莫司为基础的多靶点治疗疗效显著，但感染风险仍是一个令人担忧的问题。在本研究中，我们阐明了使用咪唑立宾而非MMF进行多靶点治疗的潜力。
对36例经活检证实为狼疮性肾炎的患者使用咪唑立宾、他克莫司和糖皮质激素进行治疗，然后进行回顾性评估。为确定疗效，评估蛋白尿缓解（≤0.2 g/天）、完全缓解（Liu等人，《内科学年鉴》162:18 - 26，2015）和系统性红斑狼疮疾病活动指数（SLEDAI）缓解率，以及第6个月和第12个月时泼尼松龙的剂量。研究血清咪唑立宾/他克莫司水平与临床参数之间的关联。为评估安全性，检查不良事件。
所有患者在12个月内均可继续原治疗方案，无需停药或病情加重。在第6个月时，蛋白尿缓解率、完全缓解率、SLEDAI缓解率和泼尼松龙剂量分别为69%、53%、36%和12.1 mg/天，而在12个月时分别为92%、67%、50%和8.8 mg/天。该治疗对每种组织学类型的肾炎以及SLE的非肾脏表现均有效。除1例因上呼吸道感染住院的患者外，未观察到包括肺炎和巨细胞病毒病在内的严重感染。他克莫司谷浓度较高与补体正常化相关，而咪唑立宾峰浓度较高与预防巨细胞病毒血症相关。
我们的结果表明，使用咪唑立宾而非MMF进行的多靶点治疗在12个月内具有高度安全性和有效性。该治疗可能使同时使用的糖皮质激素更快减量。
