Background/Purpose: It was reported in 2008 that multitarget therapy, consisting of taclorimus (TAC), mycophenolate mofetil (MMF) and glucocorticoid, is effictive and safe in induction therapy of active lupus nephritis. However, its efficacy and safety in maintenance therapy of SLE is not clarified yet. Mizoribine (MZR), an immunosuppressive drug targeting inosine monophosphate dehydrogenase, inhibits de novo pathway for purine synthesis as MMF. Recently, multitarget therapy consisting of TAC, MZR and glucocorticoid has been reported to be effective and safe in maintenance therapy, although the mode of MZR administration widely varies. Intermittent MZR pulse therapy (300mg single dose, once to four times per week) gives higher rise of peak blood concentration to suppress lymphocyte function than low dose daily therapy (50mg three times per day, total 150mg per day). It remains to be elucidated, if intermittent MZR pulse therapy is effective and safe in SLE maintenance therapy. Methods: Eleven SLE patients (2 males, 9 females) were treated with multitarget therapy with TAC and MZR pulse after the induction therapy. Demographic data, laboratory data (serum dsDNA antibody and serum CH50) and daily prednisolone (PSL) dose and SLE disease activity index (SLEDAI) score were documented at three different time points, first and second add-on of immunosuppressant and recent by medical record review. Average duration is 8.9±12.0 months between the first add-on and the second add-on, and 6.0±4.3 months between the second add-on and recent. Statistical analysis (Kruskal-Wallis test) was done using Prism version 5.0d. Adverse effects and the number of relapse were also documented. Each value was described as mean ± standard deviation. Results: Seven of 11 patients presented lupus nephritis. Three of these seven patients treated with methylprednisolone pulse therapy as induction therapy. After induction therapy, TAC in 10 patients and MZR in one patient were started at first add-on, and MZR in 10 patients and TAC in one patient were further added at second add-on. Serum CH50 level significantly increased (first add-on:31.4±11.8 U/mL, second add-on:37.7±11.8 U/mL, recent:46.5±12.7 U/mL, P=0.00252). The mean values of SLEDAI score and serum dsDNA antibody level improved, although they did not reach statistical significance (SLEDAI first add-on:4.0±2.8, second add-on:2.9±1.9, recent:1.8±1.4, P=0.1095, dsDNA first add-on:42.9±54.4, second add-on:20.0±11.2, recent:14.3±5.8, P=0.3). Daily oral prednisolone dose was significantly reduced (first add-on:26.9±13.7, second add-on:16.7±6.1, recent:10.4±5.0, P=0.0012). There was only one patient with relapse during multitarget maintenance therapy, although he treated with methylprednisolone pulse for nephritis in induction therapy. No patients had major adverse effects, resulting in the interruption of the multitarget maintenance therapy. There were three minor adverse events such as transient increase of serum creatinine level and herpes zoster in three patients. Conclusion: Multitarget maintenance therapy with TAC and MZR pulse is safe and effective enough to reduce daily steroid dose and to minimize relapse without major adverse effects in Japanese patients with SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/maintenance-therapy-with-taclorimus-and-mizoribine-pulse-in-sle/