First-line Combination Strategy Provides Favorable 5-year Outcomes for Patients with Lupus Nephritis: A Single-center Observational Study.

This observational study aimed to clarify the long-term results of the combination of mizoribine (MZB), tacrolimus (TAC) and prednisolone as first-line therapy for lupus nephritis (LN). This was our institution's standard therapy between 2009 and 2015, when we saw 36 patients with LN. When a patient thus treated achieved SLEDAI remission (= 0) and/or the prednisolone dose could be tapered to 5 mg/day, either MZB or TAC was stopped, and the other was continued for maintenance therapy. If treatment failure or relapse occurred, second-line therapy was introduced. At years 1 and 5, overall complete renal response and SLEDAI remission were 94% and 88%, and 50% and 62%, respectively. Excluding 2 cases lost to follow-up, medications after 5 years were as follows: 20 (59%) were stable on 1 drug (MZB or TAC), 11 (32%) required continuation of both drugs (MZB + TAC), and 3 (9%) required second-line therapy. The 5-year retention rate was 91% (non-secondline), with 0% of relapse in this group. Our first-line combination strategy showed high remission rates in the induction phase, and subsequent maintenance therapy demonstrated good outcomes for up to 5 years. Research that fine-tunes the order of therapeutic agents and institutes appropriate treatment goals may further improve long-term outcomes for patients with LN.

The first year results of mizoribine/tacrolimus-based multitarget treatment for consecutive patients with lupus nephritis.

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.

Optimal treatment targets for lupus nephritis using per-protocol repeat kidney biopsy findings at 2 years and clinical data up to 5 years: a single-center observational study.

Background: The criteria for remission in both clinical and pathological contexts for lupus nephritis (LN) remain controversial. Objectives: To identify optimal short-term goals (remission criteria) for LN predicting long-term success at 5 years, using repeat kidney biopsy (Biopsy 2) and clinical data. Design: Single-center observational study. Methods: Twenty-three consecutive LN patients undergoing Biopsy 2 2 years post-induction therapy were evaluated. Two ideal long-term goals at 5 years were defined as: "A," Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) = 0 and prednisolone (PSL) ⩽5 mg/day, and "B," proteinuria ⩽0.2 g/day with a normal serum creatinine level and PSL ⩽5 mg/day. Histologically, the electron-dense deposit (EDD) score grades immune deposits based on their intensity, amount, and location. A score of ⩽1 was defined as "electron microscopy remission (ER)." Results: Conventional renal indices failed to predict long-term goals. The short-term goals with an accuracy (area under the curve: 95% confidence interval) of ⩾0.8 predicted long-term goals: "A at 5 years" (A-5y), A-2y (0.91: 0.79-1.00), DORIS-R-2y (0.87: 0.72-1.00), EDD score (0.85: 0.70-1.00), B-2y (0.83: 0.66-0.99), and SLEDAI-R-2y (0.82: 0.66-0.98) as well as "B at 5 years" (B-5y), A-2y (0.87: 0.73-1.00), B-2y (0.87: 0.73-1.00), EDD score (0.85: 0.69-1.00), and DORIS-R-2y (0.83: 0.67-0.99). EDD scores predicted A-5y, B-5y, and PSL dose at 5 years in proportion to the score. The clinical and histological goals aligned. Conclusion: The best predictive short-term goal was A-2y. Concordance between clinical remission (A-2y, B-2y, and DORIS-R-2y) and histological remission (ER) at 2 years suggests optimal short-term goals for LN.

Mizoribine, tacrolimus, and corticosteroid combination therapy successfully induces remission in patients with lupus nephritis.

BACKGROUND: Conventional cyclophosphamide-based treatment regimens for lupus nephritis (LN) are still not considered to be optimal. The aim of this study was to evaluate the efficacy and safety of mizoribine, tacrolimus, and corticosteroid combination therapy for LN. METHODS: We retrospectively evaluated a combination treatment of mizoribine and tacrolimus with corticosteroids as induction therapy in eight newly diagnosed systemic lupus erythematosus (SLE) patients with biopsy-proven LN. RESULTS: All patients were women, and their mean [standard deviation (SD)] age was 48.5 (20) years. All patients (100 %) had positive anti-double-stranded DNA (anti-dsDNA) antibody titers, and four (50.0 %) were nephrotic. Mean (SD) serum creatinine and daily proteinuria levels were 0.72 (0.4) mg/dl (range 0.33-1.55 mg/dl) and 4.56 (2.8) g (range 0.77-8.2 g), respectively. By month 2, significant improvements in the anti-dsDNA antibody titers, levels of proteinuria, serum albumin, and C3, and SLE disease activity index score were observed. By month 6, seven patients (87.5 %) were in complete remission, with normalized levels of both proteinuria and serum creatinine. CONCLUSIONS: This pilot study suggests that mizoribine and tacrolimus treatment with corticosteroids is well tolerated and may prove to be an optimal alternative remission-inducing regimen for LN.