Efficacy and safety of low-dose interleukin-2 in combination with methotrexate in patients with active rheumatoid arthritis:a randomized,double-blind,placebo-controlled phase 2 trial  

作　　者：Xiaoying Zhang Miao Miao Ruijun Zhang Xu Liu Xiaozhen Zhao Miao Shao Tian Liu Yuebo Jin Jiali Chen Huixin Liu Xia Zhang Yun Li Yunshan Zhou Yue Yang Ru Li Haihong Yao Yanying Liu Chun Li Yuhui Li Limin Ren Yin Su Xiaolin Sun Jing He Zhanguo Li 

机构地区：[1]Department of Rheumatology and Immunology,Peking University People’s Hospital,100044 Beijing,China [2]Department of Rheumatology and Immunology,The First Affiliated Hospital of Wannan Medical College,241000 Wuhu,Anhui,China [3]Department of Clinical Epidemiology and Biostatistics,Peking University People’s Hospital,100044 Beijing,China [4]Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis(BZ0135),Beijing,China [5]Peking-Tsinghua Center for Life Sciences,Beijing,China [6]State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University,Beijing,China

出　　处：《Signal Transduction and Targeted Therapy》2022年第4期1194-1201,共8页信号转导与靶向治疗（英文）

基　　金：National Natural Science Foundation of China(U1903210,31530020,81701598,31570880,81471601,81801617);Beijing SciTech Program(Z171100000417007,Z191100006619114);Macao Science and Technology Fund(0094/2018/A3).

摘　　要：Rheumatoid arthritis(RA)is an aggressive autoimmune arthritis,and current therapies remain unsatisfactory due to low remission rate and substantially adverse effects.Low-dose interleukin-2(Ld-IL2)is potentially a therapeutic approach to further improve the disease.This randomized,double-blind,placebo-controlled trial was undertaken to evaluate the efficacy and safety of Ld-IL2 in patients with active RA.Patients were randomly assigned(1:1)to receive Ld-IL2,defined as a dose of 1 million IU,or placebo in a 12-week trial with a 12-week follow-up.Three cycles of Ld-IL2 or placebo were administered subcutaneously every other day for 2 weeks(a total of 7 doses),followed by a 2-week break.All patients received a stable dose of methotrexate(MTX).The primary outcomes were the proportion of patients achieving the ACR20,DAS28-ESR<2.6,and the change from baseline in CDAI or SDAI at week 24.Secondary endpoints included other clinical responses and safety.The primary outcomes were achieved in the perprotocol population.The improvements from baseline in CDAI and SDAI were significantly greater across time points for the LdIL2+MTX group(n=17)than for the placebo+MTX group(n=23)(P=0.018 and P=0.015,respectively).More patients achieved ACR20 response in the Ld-IL2+MTX group than those in the placebo+MTX group at week 12(70.6%vs 43.5%)and at week 24(76.5%vs 56.5%)(P=0.014).In addition,low Treg and high IL-21 were associated with good responses to Ld-IL2.Ld-IL-2 treatment was well-tolerated in this study.These results suggested that Ld-IL2 was effective and safe in RA.ClinicalTrials.gov number:NCT 02467504.

关 键 词：PATIENTS PLACEBO METHOTREXATE 

分 类 号：R593.21[医药卫生—内科学]