Xuebing Feng1, Fei Gu1, Weiwei Chen1, Yan Liu2, Hua Wei3, Lin Liu4, Songlou Yin5, Zhanyun Da6, Lingyun Sun7. 1. Department of Rheumatology and Immunology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China. 2. Department of Rheumatology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, China. 3. Department of Rheumatology and Immunology, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu 225001, China. 4. Department of Rheumatology and Immunology, Central Hospital of Xuzhou City, Xuzhou, Jiangsu 221009, China. 5. Department of Rheumatology and Immunology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, China. 6. Department of Rheumatology and Immunology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China. 7. Department of Rheumatology and Immunology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China. Email: lingyunsun2012@163.com.
Abstract
BACKGROUND: Lupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus. Although there have been substantial improvements in LN treatment over the last decade, the outcome remains unoptimistic in a considerable percentage of patients. The aim of this study was to evaluate the efficacy and safety of mizoribine (MZR), a novel selective inhibitor of inosine monophosphate dehydrogenase, as induction treatment for active LN in comparison with mycophenolate mofetil (MMF) and intravenous cyclophosphamide (CYC). METHODS:Ninety patients with active LN were observed. Thirty patients were given MZR orally at the dose of 300 mg every other day. Thirty patients tookMMF at 2 g per day in two divided doses. Thirty patients received CYC intravenously 0.5 g every 2 weeks. Therapeutic effects and adverse events (AEs) were evaluated at the end of 24-week treatment. One-way analysis of variance (ANOVA) followed by Dunn's test was applied to compare the difference among the groups. For comparing categorical data between two groups, χ(2) test was employed. RESULTS: Early responses at week 12 were achieved by 73.3%, 90.0%, and 96.7% in MZR, MMF, and CYC groups, respectively. There was no significant difference in the complete remission rates (22.7%, 24.0%, and 25.0%, respectively) or overall response rates (68.2%, 72.0%, and 75.0%, respectively) among the three groups at week 24. The most prominent drop-down of Systemic Lupus Erythematosus Disease Activity Index scores was observed in MMF or CYC group, and the decline of health assessment questionnaire scores in MZR or MMF group was more prominent than that in the CYC group at week 12. Serum complement 3 (C3) or C4 levels were elevated in all groups after the treatments. CYC was more effective in inhibiting anti-double-stranded DNA antibody, while MZR was more effective in inhibiting antinuclear antibody. The incidences of AEs in patients treated with CYC were significantly higher than those in patients treated with MZR or MMF (24.2% for CYC vs. 3.3% for MZR, and 2.6% for MMF, P = 0.01). CONCLUSIONS:MZR is well tolerated and has an effect similar to MMF in the induction therapy of active LN. MZR may serve as an alternative approach for LN patients.
RCT Entities:
BACKGROUND:Lupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus. Although there have been substantial improvements in LN treatment over the last decade, the outcome remains unoptimistic in a considerable percentage of patients. The aim of this study was to evaluate the efficacy and safety of mizoribine (MZR), a novel selective inhibitor of inosine monophosphate dehydrogenase, as induction treatment for active LN in comparison with mycophenolate mofetil (MMF) and intravenous cyclophosphamide (CYC). METHODS: Ninety patients with active LN were observed. Thirty patients were given MZR orally at the dose of 300 mg every other day. Thirty patients took MMF at 2 g per day in two divided doses. Thirty patients received CYC intravenously 0.5 g every 2 weeks. Therapeutic effects and adverse events (AEs) were evaluated at the end of 24-week treatment. One-way analysis of variance (ANOVA) followed by Dunn's test was applied to compare the difference among the groups. For comparing categorical data between two groups, χ(2) test was employed. RESULTS: Early responses at week 12 were achieved by 73.3%, 90.0%, and 96.7% in MZR, MMF, and CYC groups, respectively. There was no significant difference in the complete remission rates (22.7%, 24.0%, and 25.0%, respectively) or overall response rates (68.2%, 72.0%, and 75.0%, respectively) among the three groups at week 24. The most prominent drop-down of Systemic Lupus Erythematosus Disease Activity Index scores was observed in MMF or CYC group, and the decline of health assessment questionnaire scores in MZR or MMF group was more prominent than that in the CYC group at week 12. Serum complement 3 (C3) or C4 levels were elevated in all groups after the treatments. CYC was more effective in inhibiting anti-double-stranded DNA antibody, while MZR was more effective in inhibiting antinuclear antibody. The incidences of AEs in patients treated with CYC were significantly higher than those in patients treated with MZR or MMF (24.2% for CYC vs. 3.3% for MZR, and 2.6% for MMF, P = 0.01). CONCLUSIONS:MZR is well tolerated and has an effect similar to MMF in the induction therapy of active LN. MZR may serve as an alternative approach for LN patients.
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