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 ther...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.展开更多
Background:Psoriatic arthritis(PsA)is an inflammatory arthropathy characterized by psoriasis and bone erosion on radiology.Dickkopf-1(Dkk-1)is considered to be the main inhibitor of the Wnt signaling pathway and resul...Background:Psoriatic arthritis(PsA)is an inflammatory arthropathy characterized by psoriasis and bone erosion on radiology.Dickkopf-1(Dkk-1)is considered to be the main inhibitor of the Wnt signaling pathway and results in reduced osteoblast proliferation.The aim of this study was to investigate the serum level of Dkk-1 and its association with bone erosion in PsA patients.Methods:Serum Dkk-1 levels were measured by enzyme-linked immunosorbent assay(ELISA)in 69 patients with PsA and 60 controls,including 39 rheumatoid arthritis(RA)patients,and 21 healthy controls(HCs).Rheumatoid factor and anti-cyclic citrullinated peptide levels were also determined by ELISA.The association of Dkk-1 level with clinical and laboratory features of PsA was analyzed.Logistic regression analysis was used to analyze the risk factors for bone erosion in PsA.Results:Dkk-1 was elevated in 68.1%(47/69)of the patients with PsA,46.2%(18/39)of RA patients,and 9.5%(2/21)of HCs.Serum Dkk-1 concentration was significantly higher in PsA patients compared with that in HCs.The level of serum Dkk-1 was correlated with a swollen joint count,and levels of complement components 3 and 4.Elevated Dkk-1 level(odds ratio=4.440,95%confidence interval:1.246-15.817,P=0.021)was identified as the risk factor for bone erosion in PsA.Conclusions:The serum level of Dkk-1 is abnormally elevated in PsA patients.The elevation of Dkk-1 might be involved in the mechanism of bone erosion in patients with PsA.展开更多
基金financially supported by grants from the Macao Science and Technology Development Fund(0003/2019/AKP,0094/2018/A3,and 0010/2020/A1)Guangdong Basic and Applied Basic Research Foundation(2020B1515130005)Guangdong-Hong Kong-Macao Joint Lab on Chinese Medicine and Immune Disease Research,Guangzhou University of Chinese Medicine(2020B1212030006).
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).
文摘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.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 31530020, No. 81471601, and No. 81671602） and the Beijing Nova Program （No. Z 171100001117025）.
基金supported by grants from the National Natural Science Foundation of China(Nos.81771678,81801617)。
文摘Background:Psoriatic arthritis(PsA)is an inflammatory arthropathy characterized by psoriasis and bone erosion on radiology.Dickkopf-1(Dkk-1)is considered to be the main inhibitor of the Wnt signaling pathway and results in reduced osteoblast proliferation.The aim of this study was to investigate the serum level of Dkk-1 and its association with bone erosion in PsA patients.Methods:Serum Dkk-1 levels were measured by enzyme-linked immunosorbent assay(ELISA)in 69 patients with PsA and 60 controls,including 39 rheumatoid arthritis(RA)patients,and 21 healthy controls(HCs).Rheumatoid factor and anti-cyclic citrullinated peptide levels were also determined by ELISA.The association of Dkk-1 level with clinical and laboratory features of PsA was analyzed.Logistic regression analysis was used to analyze the risk factors for bone erosion in PsA.Results:Dkk-1 was elevated in 68.1%(47/69)of the patients with PsA,46.2%(18/39)of RA patients,and 9.5%(2/21)of HCs.Serum Dkk-1 concentration was significantly higher in PsA patients compared with that in HCs.The level of serum Dkk-1 was correlated with a swollen joint count,and levels of complement components 3 and 4.Elevated Dkk-1 level(odds ratio=4.440,95%confidence interval:1.246-15.817,P=0.021)was identified as the risk factor for bone erosion in PsA.Conclusions:The serum level of Dkk-1 is abnormally elevated in PsA patients.The elevation of Dkk-1 might be involved in the mechanism of bone erosion in patients with PsA.
