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The First Year Results of mizoribine/tacrolimus-based Multitarget Treatment for Consecutive Patients With Lupus Nephritis

Hidetoshi Kagawa, Tsutomu Hiromasa, Ryutaro Yamanaka, Reika Hayashi, Yoko Tsunashima, Tatsuyuki Inoue, Ken-Ei Sada

Clin Exp Nephrol. 2018 Dec;22(6):1371-1378.

PMID: 29948442

Abstract:

Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP50924497 Mizoribine Mizoribine 50924-49-7 Price
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