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Combined immunosuppressive treatment (CIST) in lupus nephritis: a multicenter, randomized controlled study

  • Yuan An
  • Yunshan Zhou
  • Liqi Bi
  • Bo Liu
  • Hong Wang
  • Jin Lin
  • Danyi Xu
  • Mei Wang
  • Jing Zhang
  • Yongfu Wang
  • Yan An
  • Ping Zhu
  • Ronghua Xie
  • Zhiyi Zhang
  • Yifang Mei
  • Xiangyuan Liu
  • Xiaoli Deng
  • Zhongqiang Yao
  • Zhuoli Zhang
  • Yu Wang
  • Weiguo Xiao
  • Hui Shen
  • Xiuyan Yang
  • Hanshi Xu
  • Feng Yu
  • Guochun Wang
  • Xin Lu
  • Yang Li
  • Yingnan Li
  • Xiaoxia Zuo
  • Yisha Li
  • Yi Liu
  • Yi Zhao
  • Jianping Guo
  • Lingyun Sun
  • Minghui Zhao
  • Zhanguo Li
Original Article

Abstract

Objectives

The standard strategy for treating lupus nephritis comprises glucocorticoids together with either intravenous cyclophosphamide or oral mycophenolate mofetil, but the low remission rate is still a challenge in practice. This study was aimed to seek higher remission rate of lupus nephritis using a combined strategy.

Method

A 24-week trial was conducted in 17 rheumatology or nephrology centers in China. A total of 191 lupus nephritis patients were randomized to follow a combined immunosuppressive treatment (CIST) with intravenous cyclophosphamide, an oral immunosuppressive agent, namely mycophenolate mofetil, azathioprine or leflunomide, and hydroxychloroquine (n = 95), or receive intravenous cyclophosphamide alone (n = 96) for 24 weeks. Glucocorticoid was given to both groups. The primary end point was a complete remission with a most stringent standard as proteinuria < 150 mg per 24 h, normal urinary sediment, serum albumin, and renal function at 24 weeks. The secondary end point was treatment failure at 24 weeks.

Results

At week 24, both the rate of complete remission (39.5%) and total response (87.2%) was higher in the combined group, compared with CYC group (20.8% and 68.8%, p < 0.05). The cumulative probability of complete remission was also higher in the combined group (p = 0.013). In addition, the combined treatment was superior to routine CYC with less treatment failure (12.8% vs.31.2%, p < 0.001). No difference was found between the incidences of severe adverse events in the two arms: 3.2% (3/95 combined group) vs.4.2% (4/96 CYC group).

Conclusion

Treatment with a combined immunosuppressive agent is superior to routine CYC only therapy in lupus nephritis.

Keywords

Immunosuppressive agents Lupus nephritis Remission inducing Systemic lupus erythematosus 

Notes

Acknowledgments

We thank Hongyuan Wang (School of Public Health, Peking University) and Chunfang Zhang (Department of Clinical Epidemiology, Peking University People’s Hospital) for statistical support and interpretation of the data.

Role of the funder/sponsor

The funder had no role in collecting, analyzing, or interpreting the data, writing the report, or deciding to submit the paper for publication. All authors had full access to all of the data, made the decision to submit these data for publication, and agreed on the final content of the paper.

Funding

This study was funded by the National Basic Research Program of China (973 program) (No. 2014CB541901).

Compliance with ethical standards

Disclosures

None.

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Copyright information

© International League of Associations for Rheumatology (ILAR) 2018

Authors and Affiliations

  • Yuan An
    • 1
  • Yunshan Zhou
    • 1
  • Liqi Bi
    • 2
  • Bo Liu
    • 2
  • Hong Wang
    • 3
  • Jin Lin
    • 4
  • Danyi Xu
    • 4
  • Mei Wang
    • 5
  • Jing Zhang
    • 5
  • Yongfu Wang
    • 6
  • Yan An
    • 6
  • Ping Zhu
    • 7
  • Ronghua Xie
    • 7
  • Zhiyi Zhang
    • 8
  • Yifang Mei
    • 8
  • Xiangyuan Liu
    • 9
  • Xiaoli Deng
    • 9
  • Zhongqiang Yao
    • 9
  • Zhuoli Zhang
    • 10
  • Yu Wang
    • 10
  • Weiguo Xiao
    • 11
  • Hui Shen
    • 11
  • Xiuyan Yang
    • 12
  • Hanshi Xu
    • 12
  • Feng Yu
    • 13
  • Guochun Wang
    • 14
  • Xin Lu
    • 14
  • Yang Li
    • 15
  • Yingnan Li
    • 15
  • Xiaoxia Zuo
    • 16
  • Yisha Li
    • 16
  • Yi Liu
    • 17
  • Yi Zhao
    • 17
  • Jianping Guo
    • 1
  • Lingyun Sun
    • 3
  • Minghui Zhao
    • 13
  • Zhanguo Li
    • 1
  1. 1.Department of Rheumatology and ImmunologyPeking University People’s HospitalBeijingChina
  2. 2.Department of Rheumatology, China Japan Union HospitalJilin UniversityChangchunChina
  3. 3.Department of Rheumatology and ImmunologyThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingChina
  4. 4.Department of Rheumatology and Immunology, First Affiliated HospitalZhejing UniversityHangzhouChina
  5. 5.Department of NephrologyPeking University People’s HospitalBeijingChina
  6. 6.Department of RheumatologyFirst Affiliated Hospital of Baotou Medical CollegeBaotouChina
  7. 7.Department of Clinical ImmunologyFourth Military Medical University Xijing HospitalXi’anChina
  8. 8.Department of Rheumatology and ImmunologyThe First Affiliated Hospital of Harbin Medical UniversityHarbinChina
  9. 9.Department of Rheumatology and ImmunologyPeking University Third HospitalBeijingChina
  10. 10.Department of Rheumatology and ImmunologyPeking University First HospitalBeijingChina
  11. 11.Department of Rheumatology and ImmunologyFirst Affiliated Hospital of China Medical UniversityShenyangChina
  12. 12.Department of RheumatologyFirst Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina
  13. 13.Department of NephrologyPeking University First HospitalBeijingChina
  14. 14.Department of Rheumatology and ImmunologyChina-Japan Friendship HospitalBeijingChina
  15. 15.Department of Rheumatology and Immunology, Second Clinical HospitalHarbin Medical UniversityHarbinChina
  16. 16.Department of Rheumatology and ImmunologyXiangya Hospital Central South UniversityChangshaChina
  17. 17.Department of Rheumatology and Immunology, West China HospitalSichuan UniversityChengduChina

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