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, Kenei Sada

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalClinical and Experimental Nephrology
DOIs
Publication statusAccepted/In press - Jun 9 2018

Fingerprint

Lupus Nephritis
Tacrolimus
Mycophenolic Acid
Prednisolone
Cytomegalovirus
Proteinuria
Systemic Lupus Erythematosus
Glucocorticoids
Therapeutics
Nephritis
Viremia
Infection
Respiratory Tract Infections
bredinin
Pneumonia
Biopsy
Safety
Serum

Keywords

  • Cytomegalovirus
  • Lupus nephritis
  • Mizoribine
  • Multitarget therapy
  • Tacrolimus

ASJC Scopus subject areas

  • Physiology
  • Nephrology
  • Physiology (medical)

Cite this

The first year results of mizoribine/tacrolimus-based multitarget treatment for consecutive patients with lupus nephritis. / Kagawa, Hidetoshi; Hiromasa, Tsutomu; Yamanaka, Ryutaro; Hayashi, Reika; Tsunashima, Yoko; Inoue, Tatsuyuki; Sada, Kenei.

In: Clinical and Experimental Nephrology, 09.06.2018, p. 1-8.

Research output: Contribution to journalArticle

Kagawa, Hidetoshi ; Hiromasa, Tsutomu ; Yamanaka, Ryutaro ; Hayashi, Reika ; Tsunashima, Yoko ; Inoue, Tatsuyuki ; Sada, Kenei. / The first year results of mizoribine/tacrolimus-based multitarget treatment for consecutive patients with lupus nephritis. In: Clinical and Experimental Nephrology. 2018 ; pp. 1-8.
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AU - Hiromasa, Tsutomu

AU - Yamanaka, Ryutaro

AU - Hayashi, Reika

AU - Tsunashima, Yoko

AU - Inoue, Tatsuyuki

AU - Sada, Kenei

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AB - 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.

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KW - Lupus nephritis

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KW - Multitarget therapy

KW - Tacrolimus

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