Efficacy of weekly mizoribine pulse therapy in refractory lupus nephritis

Oxford University Press (OUP) - Tập 23 - Trang 97-103 - 2012
Eiko Nishi1, Hideto Kameda2, Hiroe Ogawa1, Hayato Nagasawa1, Hirofumi Takei1, Ayumi Okuyama1, Takahiko Kurasawa2, Tsuneo Kondo1, Koji Nishimura1, Yuichiro Shirai2, Ryota Sakai1, Tatsuya Ito1,3, Tsutomu Takeuchi2, Koichi Amano1
1Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan
2Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan
3Department of Internal Medicine, Saitama Yorii Hospital, Yorii, Japan

Tóm tắt

We investigated the efficacy of a high-dose intermittent dosing treatment method (weekly mizoribine pulse therapy) conceived in the hope of achieving better efficacy by increasing the peak blood levels of mizoribine in patients with refractory lupus nephritis. Seventeen patients with lupus nephritis who had been resistant to corticosteroid and immunosuppressant therapy received weekly mizoribine pulse therapy. Mizoribine (350 mg) was administered three times at 12 h intervals over 2 consecutive days (700 mg for day 1 and 350 mg for day 2), followed by a washout period from day 3 to day 7. This therapeutic strategy enabled the peak blood levels of mizoribine to be increased to more than 3 μg/mL in most of the patients. Although SLEDAI, anti-ds-DNA antibody titer, CH-50, and serum albumin level did not significantly improve, urinary protein levels decreased, and it was possible to taper the dose of concomitant steroids. Using our definition of clinical response, 10 of the 17 patients were responders and 4 of them were nonresponders. The average peak serum mizoribine concentration of the responders was as high as 3.5 μg/mL. Elevation of serum liver enzymes was seen in 1 patient, and hyperuricemia occurred in 4 cases, but none of these adverse events were serious. Intermittent administration of mizoribine can increase blood levels and may be effective for refractory lupus nephritis.

Tài liệu tham khảo

Bertsias G, Boumpas DT. Lupus nephritis—winning a few battles but not the war. Nat Rev Rheumatol. 2011;7:441–2.

Houssiau FA, Vasconcelos C, D’Cruz D, Sebastiani GD, Garrido Ed Ede R, Danieli MG, et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum. 2002;46:2121–31.

Contreras G, Pardo V, Leclercq B, Lenz O, Tozman E, O’Nan P, Roth D. Sequential therapies for proliferative lupus nephritis. N Engl J Med. 2004;350:971–80.

Ogawa H, Kameda H, Amano K, Takeuchi T. Efficacy and safety of cyclosporine A in patients with refractory systemic lupus erythematosus in a daily clinical practice. Lupus. 2010;19:162–9.

Ishikawa H. Mizoribine and mycophenolate mofetil. Curr Med Chem. 1999;6:575–97.

Houssiau FA, D’Cruz D, Sangle S, Remy P, Vasconcelos C, MAINTAIN Nephritis Trial Group, et al. Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial. Ann Rheum Dis. 2010;69:2083–9.

Appel GB, Contreras G, Dooley MA, Ginzler EM, Isenberg D, Jayne D, Aspreva Lupus Management Study Group, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009;20:1103–12.

Sugitani A, Kitada H, Ota M, Yoshida J, Doi A, Hirakata H. Revival of effective and safe high-dose mizoribine for the kidney transplantation. Clin Transpl. 2006;20:590–5.

Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002;29:288–91.

Hosotsubo H, Takahara S, Taenaka N. Simplified high-performance liquid chromatographic method for determination of mizoribine in human serum. J Chromatogr. 1988;432:340–5.

Homma M, Akizuki M, Yokobari R, Hashimoto H, Kashiwazaki S, Kondo H, et al. Clinical evaluation of mizoribine on lupus nephritis. Rinsyo-Iyaku. 1989;5(4):795–824 (in Japanese).

Kuroda T, Hirose S, Tanabe N, Sato H, Nakatsue T, Ajiro J, et al. Mizoribine therapy for patients with lupus nephritis: the association between peak mizoribine concentration and clinical efficacy. Mod Rheumatol. 2007;17:206–12.

Sonda K, Takahashi K, Tanabe K, Funchinoue S, Hayasaka Y, Kawaguchi H, et al. Clinical pharmacokinetic study of mizoribine in renal transplantation patients. Transpl Proc. 1996;28:3643–8.

Turka LA, Dayton J, Sinclair G, Thompson CB, Mitchell BS. Guanine ribonucleotide depletion inhibits T cell activation. Mechanism of action of the immunosuppressive drug mizoribine. J Clin Invest. 1991;87:940–8.

Hirohata S, Nakanishi K, Yanagida T. Inhibition of cyclin A gene expression in human B cells by an immunosuppressant mizoribine. Clin Exp Immunol. 2000;120:448–53.

Takahashi S, Wakui H, Gustafsson JA, Zilliacus J, Itoh H. Functional interaction of the immunosuppressant mizoribine with the 14-3-3 protein. Biochem Biophys Res Commun. 2000;274:87–92.

Ishida K, Kaneda H, Uemura O, Ushijima K, Ohta K, Goto Y, et al. Evaluation of limited sampling designs to estimate maximal concentration and area under the curve of mizoribine in pediatric patients with renal disease. Drug Metab Pharmacokinet. 2011;26:71–8.

Stypinski D, Obaidi M, Combs M, Weber M, Stewart AJ, Ishikawa H. Safety, tolerability and pharmacokinetics of high-dose mizoribine in healthy male volunteers. Br J Clin Pharmacol. 2006;63:459–68.

Yumura W, Uchida K, Kawashima A, Kobayashi H, Miwa N, Honda K et al. Evaluation of plasma concentration of mizoribine as an immunosuppressive agent in lupus nephritis patients. Kidney Dial. 1999;47:705–8. (in Japanese).

Doi T, Masaki T, Shiraki N, Kawai T, Yorioka N. Oral mizoribine pulse therapy for steroid-dependent focal segmental glomerulosclerosis. Clin Nephrol. 2008;69:433–5.

Tanaka H, Tsugawa K, Nakahata T, Kudo M, Suzuki K, Ito E. Implication of the peak serum level of mizoribine for control of the serum anti-dsDNA antibody titer in patients with lupus nephritis. Clin Nephrol. 2005;63:417–22.

Tanaka H, Tsugawa K, Oki E, Suzuki K, Ito E. Long-term mizoribine intermittent pulse therapy for young patients with flare of lupus nephritis. Clin Rheumatol. 2008;27:85–9.

Suzuki K, Kameda H, Amano K, Nagasawa H, Takei H, Nishi E, et al. Single center prospective study of tacrolimus efficacy and safety in the treatment of various manifestations of systemic lupus erythematosus. Rheumatol Int. 2011;31:757–63.

Bao H, Liu Z-H, Xie H-L, Hu W-X, Zhang H-T, Li L-S. Successful treatment of class V + IV lupus nephritis with multitarget therapy. J Am Soc Nephrol. 2008;19:2001–10.

Aizawa-Yashiro T, Tsuruga K, Watanabe S, Oki E, Ito E, Tanaka H. Novel multidrug therapy for children with cyclosporine-resistant or -intolerant nephrotic syndrome. Pediatr Nephrol. 2011;26:1255–61.

Thông tin
Thông tin xuất bản

Oxford University Press (OUP)

Tập 23

97-103

Thông tin tác giả