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Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: a randomised, double-blind, placebo-controlled trial
  1. Jing He1,2,
  2. Ruijun Zhang1,
  3. Miao Shao1,2,
  4. Xiaozhen Zhao1,
  5. Miao Miao1,
  6. Jiali Chen1,
  7. Jiajia Liu1,
  8. Xiaoying Zhang1,
  9. Xia Zhang1,
  10. Yuebo Jin1,
  11. Yu Wang3,
  12. Shilei Zhang4,
  13. Lei Zhu1,
  14. Alexander Jacob5,
  15. Rulin Jia1,
  16. Xujie You1,
  17. Xue Li1,
  18. Chun Li1,
  19. Yunshan Zhou1,
  20. Yue Yang1,
  21. Hua Ye1,
  22. Yanying Liu1,
  23. Yin Su1,
  24. Nan Shen6,
  25. Jessy Alexander5,
  26. Jianping Guo1,2,
  27. Julian Ambrus5,
  28. Xin Lin4,
  29. Di Yu6,7,
  30. Xiaolin Sun1,2,
  31. Zhanguo Li1,2,8
  1. 1 Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China
  2. 2 Beijing Key Laboratory for Rheumatism and Immune Diagnosis (BZ0135), Beijing, China
  3. 3 Center for Applied Statistics and School of Statistics, Renmin University of China, Beijing, China
  4. 4 Department of Basic Medical Sciences, Tsinghua University School of Medicine, Beijing, China
  5. 5 Department of Medicine, SUNY at Buffalo School of Medicine, Buffalo, New York, USA
  6. 6 Department of Rheumatology and Immunology,China-Australia Centre for Personalised Immunology, Shanghai Renji Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
  7. 7 Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Shanghai, China
  8. 8 State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China
  1. Correspondence to Dr Jing He, Department of Rheumatology and Immunology, Peking University People's Hospital Beijing China, Beijing 100044, China; hejing1105{at}; Professor Di Yu, Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, Australia; di.yu{at}; Dr Xiaolin Sun, Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China; sunxiaolin_sxl{at}; Professor Zhanguo Li, Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China; li99{at}


Objectives Open-labelled clinical trials suggested that low-dose IL-2 might be effective in treatment of systemic lupus erythematosus (SLE). A double-blind and placebo-controlled trial is required to formally evaluate the safety and efficacy of low-dose IL-2 therapy.

Methods A randomised, double-blind and placebo-controlled clinical trial was designed to treat 60 patients with active SLE. These patients received either IL-2 (n=30) or placebo (n=30) with standard treatment for 12 weeks, and were followed up for additional 12 weeks. IL-2 at a dose of 1 million IU or placebo was administered subcutaneously every other day for 2 weeks and followed by a 2-week break as one treatment cycle. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. The secondary endpoints were other clinical responses, safety and dynamics of immune cell subsets.

Results At week 12, the SRI-4 response rates were 55.17% and 30.00% for IL-2 and placebo, respectively (p=0.052). At week 24, the SRI-4 response rate of IL-2 group was 65.52%, compared with 36.67% of the placebo group (p=0.027). The primary endpoint was not met at week 12. Low-dose IL-2 treatment resulted in 53.85% (7/13) complete remission in patients with lupus nephritis, compared with 16.67% (2/12) in the placebo group (p=0.036). No serious infection was observed in the IL-2 group, but two in placebo group. Besides expansion of regulatory T cells, low-dose IL-2 may also sustain cellular immunity with enhanced natural killer cells.

Conclusions Low-dose IL-2 might be effective and tolerated in treatment of SLE.

Trial registration number Registries (NCT02465580 and NCT02932137).

  • systemic lupus erythematosus
  • t cells
  • Autoimmune diseases
  • cytokines
  • treatment

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  • Handling editor Josef S Smolen

  • JH, RZ and MS contributed equally.

  • Contributors JH, DY, XS and ZL initiated the investigation, led the clinical experiments, and wrote, reviewed and edited the manuscript. RZ, MS, XS, JH, DY and YW obtained and analysed the data and wrote, edited and reviewed the manuscript. JA, JA, AJ obtained data and wrote, edited and reviewed the manuscript. YW provided statistical guidance prior to study implementation, conducted statistical analysis, and edited and reviewed the manuscript. XZ, JC, YJ, XL, XZ, CL, YZ, YY, HY, YL and YS implemented the double-controlled study and reviewed and edited the manuscript. SZ, LZ, RJ, XZ, NS, JG and XL contributed to the design and implemented FACS experiments of the study. NS reviewed and edited the manuscript. All authors gave final approval of the manuscript version to be published.

  • Funding The work was supported by the National Natural Science Foundation of China (31530020,31570880,81471601,81601417 and 81701598), Peking-Tsinghua Center for Life Sciences to ZG LI, Beijing Sci-Tech Committee Z171100000417007,Clinical Medicine Plus X-Young Scholars Project of Peking University (PKU2019LCXQ013) supported by the Fundamental Research Funds for the Central Universities, Beijing Nova Program Z171100001117025, National Key Research and Development Program of China (2017YFC0909003 to DY), Bellberry-Viertel Senior Medical Research Fellowship to DY and Beijing SL PHARM.

  • Competing interests None declared.

  • Patient consent for publication Obtained.

  • Ethics approval Peking University People’s Hospital Ethics Committee approved the protocol and all patients provided written informed consent.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request.

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