AB0616 Efficacy and safety of multi-target therapy with mizoribine and tacrolimus for systemic lupus erythematosus with or without active nephritis
Authors: A. Nomura, M. Kishimoto, H. Shimizu, Y. Suyama, R. Rokutanda, Y. Ohara, K. Yamaguchi, M. Okada
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Prognosis of systemic lupus erythematosus (SLE) has improved with introduction of various immunosuppressants, but still there is room for improvement as to efficacy and safety. Bao et al. suggested more efficacy and safety of combination therapy with glucocorticoid, mycophenolate mofetil (MMF), and tacrolimus than intravenous cyclophosphamide-based regimen for class 5+4 lupus nephritis (LN). Multi-target therapy with combination of immunosuppressants targeting different sites of immune system may have better efficacy and safety requiring less dosage of each agents compared to conventional therapy using single agents. <h3>Objectives</h3> To investigate the efficacy and safety of combination therapy of glucocorticoid, mizoribine (MZR), an imidazole nucleoside having effect similar to MMF, and taclorimus for the treatment of SLE and lupus nephritis. <h3>Methods</h3> We retrospectively assessed medical records of SLE patients who started combination therapy of glucocorticoid, MZR and tacrolimus during the course of treatment between August 2008 and June 2011 at St Luke's international hospital, Tokyo. We defined cases as having active nephritis if they had newly diagnosed or worsening proliferative nephritis at the beginning of combination therapy. <h3>Results</h3> These 12 cases were all successfully treated without sever adverse events. Multi-target therapy combining glucocorticoid, MZR and tacrolimus may be more effective and safer than conventional treatments.Among 12 patients, 6 were treated with this combination therapy for their active LN (2 Class 3, 1 Class 4, 1 Class 5, 1 Class 4+5, and 1 without renal biopsy). Mean starting dose of glucocorticoid was 66.6mg equivalent of prednisolone, with pulse methylprednisolone in 4 cases. Mean doses of glucocorticoid were 7.05mg and 4.74mg at 6 month and 12 month, respectively, after starting combination therapy. Starting doses of MZR and tacrolimus were 150mg and 3mg respectively and titrated depending on the course. Five in 6 patients achieved complete remission and 1 was in partial remission at 6 month and all 5 patients who reached 12 month analysis were in complete remission. Another 6 patients started this combination regimen to treat minor flares or for the purpose of steroid sparing. Mean prednisolone doses were reduced from 11.0mg at baseline to 6.6mg at 12 month. Among all 12 patients, minor adverse events were seen in 6 patients including 3 minor infections; One subsequently stopped tacrolimus because of suspected toxicity, but other events had little impact on the treatment courses. <h3>Conclusions</h3> These 12 cases were all successfully treated without sever adverse events. Multi-target therapy combining glucocorticoid, MZR and tacrolimus may be more effective and safer than conventional treatments. <h3>References</h3> Bao H, Liu ZH, Wie HL, et al. Successful treatment of class 5+4 lupus nephritis with multitarget therapy. J Am Soc Nephrol 2008; 19: 2001-10 Yumura W, Suganuma S, Uchida K, et al. Effect of long-term treatment with mizoribine in patients with proliferative lupus nephritis. Clin Nephrol. 2005; 64: 28-34 Lanata CM, Mahmood T, Fine DM, et al. Combination therapy of mycophenolate mofetil and tacrolimus in lupus nephritis. Lupus 2010; 19: 935-40 <h3>Disclosure of Interest</h3> None Declared