ABSTRACT
Objective To observe the changes of number and proportion of CD4+CD25+FOXP3+ cells in peripheral blood of active rheumatoid arthritis patients (RA),and explore the function of recombinant human TNFR Ⅱ-Fc on the CD4+CD25-FOXP3+ Treg cells.Methods ① Forty severe RA patients were selected,who were divided into the combined treatment group (TNFR Ⅱ-Fc+MTX) and MTX only group according to the principle of randomized,double-blind,parallel and placebo-controlled study.All patients were treated for 12 weeks.Flow cytometry was used to analyze and compare the expression ratio of CD4+CD25+FOXP3 +Treg cells of RA patients' peripheral blood.Forty healthy controls were selected for parallel comparison.② VAS,DAS28,HAQ average of the two groups at different periods were compared.Matched t test was used to examine the quantity data between the groups.Results ① The proportion of CD4+CD25+FOXP3+ cells in the peripheral blood of active rheumatoid arthritis patients was significantly lower than healthy group [ (5.4±1.4)％ vs ( 7.5±1.5 )％,P＜0.01 ].The proportion of CD4+CD25+ FOXP3+ Treg cells in combined treatment group was significantly higher [(7.0+1.2)％ vs (5.2±1.6)％,P＜0.01 ] after TNFR Ⅱ-Fc and MTX combination therapy for 12 weeks.The increase rate of CD4+CD25+FOXP3+Treg cells in combined treatment group was evidently more remarkable than MTX only group [ (7.0 ± 1.2)％ vs (5.6 ±0.7 )％,P＜0.01].② After 12 weeks treatment,the arerage scores of VAS,DAS28 and HAQ of the combined treatment group were better than MTX only group,and the difference was statistically significant (P＜0.01).Conclusion This study has shown that the healing effect of TNFR Ⅱ -Fc combined with MTX is better than MTX only.TNFR Ⅱ -Fc can restore and improve the proportion of CD4+CD25+FOXP3+ Treg cells in active RA patients,which is likely to be an important mechanism for the treatment of RA patients.
ABSTRACT
ObjectiveTo evaluate the clinical and radiological efficacy of TNFR Ⅱ -Fc combined with methotrexate( MTX ) in treatment of patients with moderate and severe rheumatoid arthritis.MethodsThree hundred and ninty-six RA patients were randomized into the combined treatment group,the TNFR Ⅱ -Fc only group and MTX only group.All patients were treated for 24 weeks.ACR-N,ACR20,ACR50,ACR70,DAS28-ESR and Sharp score of both hands were measured for efficacy,and the side-effects were analyzed by one-way ANOVA.Results After 24-week therapy,the ACR-N of the combined treatment group [( 12.79±9.24)％-year] was significantly improved than that of the TNFR Ⅱ-Fc only group [(9.56±11.16)％-year,P＜0.05] and that of the MTX only group[(5.08±11.10)％-year,P＜0.05],and the TNFR Ⅱ-Fc group was significantly improved than that of the MTX group(P＜0.05).The ACR20 response rate of the combined group(80.4％) was significantly higher than that of the TNFR Ⅱ -Fc group(71.1％,P＜0.05) and the MTX group(56.7％,P＜0.01 ).The ACRS0 response rate of the combined group(53.6％) was significantly higher than that of the MTX group(30.8％,P＜0.01 ).The ACR70 response rate of the combined group was 27.7％,which was significantly different from that of the TNFR Ⅱ -Fc group (15.8％) and MTX group (7.7％,P＜0.05or P＜0.01 ).DAS28-ESR in the combination group was significantly reduced than those of the TNFR Ⅱ -Fc group and MTX group,and the DAS28-ESR of the TNFR Ⅱ -Fc group was significantly reduced than MTX group.The average total Sharp score of both hands,which demonstrated the radiographic changes,was significantly reduced in the combination group than the MTX group(P=0.03).The total adverse events in the combined group(40.9％) was significantly high than that of the MTX group(28.8％,P＜0.05).Conclusion TNFR Ⅱ -Fc combined with MTX can effectively control the activity of RA and radiological progress.