The impact of anti-TNF rcMAb to Th cell subsets of rheumatoid arthritis / 中华风湿病学杂志

Objective To explore the effect of anti-TNF rcMAb in the treatment of patients with rheumatoid arthritis (RA) and its effect on peripheral blood Th1,Th17 and Treg cells.Methods Fifty rigorously screened RA patients were randomly divided to the therapy group (n=40) who received the combined treatment of anti-TNF rcMAb and MTX,and control group (n=10) who were given MTX along with placebo,both at week 0,2,6,and 14.The clinical data of the two groups were observed and accessed respectively at week 0 and 18.In addition,the percentage of Th1,Th17,Treg cells in the peripheral blood and the relative gene expressions of transcription factors T-bet,RORC,Foxp3 in these patients were also observed respectively before and after treatment.We used t inspection and x2 inspection as the statistical analysis methods in conducting this study.Results Comparing with the control group,more patients achieved ACR20,ACR50 and ACR70 response in the combined therapy group (Z=1.671,P=0.000 94).The percentage of peripheral blood Th1 cells decreased [week 0:(7.1±3.9)％; week 18:(4.2±2.8)％] and the percentage of Treg cells obviously increased [week 0:(1.5±0.8)％; week 18:(3.0±0.6)％,t=2.301,P=0.048] in the combined therapy recipients,while the percentage of Th1 cells fell [week 0:(9.1±3.1)％; week 18:(5.8±2.6)％] and that of Treg cells slightly increased [week 0:(1.2±0.6)％; week 18:(2.2±0.6)％] in the controls.The mRNA expressions of RORC and T-bet,the transcription factors of Th17 and Th1,were decreased respectively and that of Foxp3,the transcription factor of Treg,were elevated in both groups.Conclusion The combined therapy of anti-TNF rcMAb and MTX is very effective in RA patients.Good outcome is likely achieved by modifying the peripheral blood Th cell subsets in patients with RA.

The impact of infliximab on RANK/RANKL/OPG system in rheumatoid arthritis / 中华风湿病学杂志

Objective Infliximab is a kind of recombinant human mouse chimeric anti-tumor necrosis factor monoclonal antibody. Here we aimed to examine the impact of infliximab therapy on RANK/RANKL/OPG system in the peripheral blood of rheumatoid arthritis (RA) patients. Methods Fifty patients with RA were rigorously screened and randomly divided into 2 groups. One group was treated with infliximab (3 mg/kg)and methotrexate (MTX). As control, the other group was treated with MTX alone. Infliximab was administered at weeks 0, 2, 6 and 14. The expression of RANK, RANKL mRNA in the peripheral blood, serum OPG and clinical indicators changes at week 0 and 18 were compared.x2-test or t-test were used for statistical analysis.Results After treated with infliximab, bone damage of joints were slowed down when examined by radiography in RA patients compared with the control group. And the ratio of OPG/RANKL was also decreased in RA peripheral blood (w0: 80.25;w 18: 63.2); (control group w0: 83.37; w18: 30.87)(P＞0.05). Although after the treatment with either MTX alone [w0: (238±15) pg/ml; w18: (118±10) pg/ml] or infliximab combined with MTX [(w0: (223.1±6.2) pg/ml; w18:(162.4±5.5) pg/ml], the serum levels of OPG were all decreased (P＞0.05), the level of OPG in infliximab treatment group was declined slower than those in the control group. Conclusion RA bone destruction can be inhibited by the combination therapy of infliximab and MTX. The mechanism may be partly through the RANK/RANKL/OPG system.

Effectiveness of type Ⅱ collagen from Zaocys dhumnades (Cantor) on the immune functions of rats with collagen-induced arthritis / 中华风湿病学杂志

Objective To study the effect of type Ⅱ collagen (C Ⅱ) from Zaoeys dummies (Cantor)on the immune functions of rats with collagen-induced arthritis and to understand the mechanisms of RA treated with Zaoeys dhumnades (Cantor).Methods The rats with collagen-induced arthritis were randomly divided into three group:C Ⅱ from Zaocys dhumnades,bovine C Ⅱ and arthritis control group,a normal control group was set up,too.Every group had 7 rats.The C Ⅱ from Zaocys dhumnades and the bovine C Ⅱ group were fed with C Ⅱ from Zaocys dhumnades (15 mg/kg) and bovine C Ⅱ (15 mg/kg) per day respectivelyfor 15 days.The CD4/CD8 subset ratio,serum levels of anti-C Ⅱ antibody,TNF-a,IL-10,IL-1 and IL-4 in.rats were measured.Results In the arthritis group,CD4/CD8 subset ratio (P＜0.05) and serum levels of type Ⅱ collagen antibody (P＜0.01) and TNF-a (P＜0.01) were significant increased and IL-10 (P＜0.01) was significantly decreased.In the C Ⅱ from Zaocys dhumnades and bovine C Ⅱ group,CD4/CD8 subset ratio (P＜0.05) and the level of TNF-a (P＜0.01) were significantly decreased compared with the arthritis group,and had no difference compared with the normal group.The level of anti-C Ⅱ antibody was declined significantly compared with the arthritis group (P＜0.05) and had statistical difference with the normal group (P＜0.01).The level of IL-10 was significantly increased(P＜0.01),but lower than the normal group(P＜0.05).There was no statistical difference in the level of IL-1 and IL--4 in.all four groups.Conclusion C Ⅱ from Zaoeys dhum-nades (Cantor) is as effective as bovine C Ⅱ in modifying the immune functions of collagen-induced arth-ritis in rats.They can decrease the level of anti-C Ⅱ antibody,the level of TNF-a,CD4/CD8 subset ratio and increase the level of IL-10 in the peripheral blood of rats with collagen-induced arthritis.C Ⅱ from Zaocys dhumnades may be one of the important pharmacological active components that have the potential in treating rheumatoid arthritis.

Activation and clonal expansion of T cells in the synovial fluid and peripheral circulation in patients with rheumatoid arthritis / 中华风湿病学杂志

Objective To explore the difference between T cells in the synovial fluid and peripheral blood in patients with rheumatoid arthritis(RA). Method Samples from 22 patients were studied. The differentiation and activation markers expressed on T cell surface were detected by immunofluorscence using flow cytometer. The specific proliferation of collagen Ⅱ and heat shock protein 70 was analyzed using standard 3H-TdR incorporation method. Restricted V beta usage of these T cell was analyzed by semi-quantitied RT-PCR. Results The majority of the T cell subsets in the synovial fluid were demonstrated to be CD4 and CD8 positive cells in which (40?10)% were CD4 positive and (36?16)% were CD8 T cells respectively. The ratio between CD4 and CD8 was much lower than that found in the PBL of RA patients. The percentage of CD3+/CD25+ T cells was (16?6)%. The specific proliferation of collagen Ⅱ and HSP70 to CD3+/CD25+ T cell was higher than that of CD3+/CD25+ negative T cells. The T cell receptor expressed on the T cells from both peripheral blood and synovial fluid were tested for ?? TCR (70?26)%. However, the T cells in the synovial fluid showed V?14,16 and 17 restriction. Conclusion The data here reported indicates that T cell subsets in the synovial fluid and peripheral blood circulation in patients with rheumatoid arthritis are different. The T cells in the synovial fluid demonstrates more activation and higher reactivation to collagen Ⅱ and HSP70. The TCR of T cells showes V?14,16 and 17 restriction.

Leflunomide, a new disease-modifying drug for treating active rheumatoid arthritis in methotrexate-controlled phase II clinical trial / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of leflunomide in comparison with methotrexate (MTX) on patients with rheumatoid arthritis (RA) in China.</p><p><b>METHODS</b>Five hundred and sixty-six patients with active rheumatoid arthritis were randomly assigned to receive leflunomide at 20 mg once daily or MTX at 15 mg once weekly in a controlled trial. Five hundred and four patients completed the 12-week treatment and some patients continued the treatment for 24 weeks.</p><p><b>RESULTS</b>Both leflunomide and MTX could improve the symptoms, signs, and joint function, but there were no changes in X-ray observations of patients with rheumatoid arthritis. In the leflunomide group, the overall rates of effectiveness at 12 weeks and 24 weeks were 86.94% and 92.31% respectively; the rates of remarkable improvement were 64.95% and 79.81% respectively. In the MTX group, the overall rates of effectiveness at 12 weeks and 24 weeks were 84.04% and 83.15% respectively; the rates of remarkable improvement were 56.81% and 75.28% respectively. According to intent-to-treat analysis, the ACR 20% response rates at 12 weeks and 24 weeks in the leflunomide group were 62.54% and 67.18% respectively, compared with 60.08% and 61.32% respectively in MTX group. No statistical differences were shown in the efficacy between the two groups (P > 0.05). The adverse events in the leflunomide group were gastrointestinal symptoms, skin rash, alopecia, nervous system symptoms, decreased leukocyte count, and elevation of alanine aminotransferase (ALT). Most of these side effects were mild and transient. The incidence of adverse events in the leflunomide group was 16.84%, significantly lower than that in MTX group (28.17%, P = 0.002).</p><p><b>CONCLUSIONS</b>Leflunomide is effective in the treatment of RA with less adverse events than MTX. Its efficacy is similar to MTX, but the incidence of adverse events and the rate of withdrawal due to adverse events were lower in the leflunomide group than in MTX group.</p>

Retrospective study of adverse events in patients with rheumatoid arthritis treated with second-line drugs / 中华流行病学杂志

<p><b>OBJECTIVE</b>To evaluate rates on the adverse side effect and discontinuation of second-line drugs frequently used in the treatment of rheumatoid arthritis (RA).</p><p><b>METHOD</b>Eight hundred and sixty-four RA patients were studied in a retrospective program.</p><p><b>RESULTS</b>Upper abdominal discomfort was most commonly seen when using second-line drugs. Rash was often associated with D-penicillamine (20.6%) and Sinomenium therapy (13.7%). Methotrexate (MTX) was uniquely characterized by substantial upper GI toxicity (32.2%) and Tripterygium wilfordii Hook. f. (TWH) (14.4%) by menstrual abnormality. Sulfasalazine users reported adverse events including upper abdominal trouble (39.0%), nausea (7.3%) and anorexia (7.3%) while the risk of GI malaise was greater. Patients taking hydroxychloroquine complained of blurred vision (19.6%) but no one went blind. Toxic side effects seemed to be the most common reasons for stoppages, and the patients taking MTX had the lowest discontinuation rate. Combination of D-penicillamine and Methotrexate did not increase the incidence of adverse events.</p><p><b>CONCLUSIONS</b>Knowledge on these different patterns of toxicity provided choices in the selection of second line agents for particular RA patients. However, long-term monitor are required when drugs are being used.</p>

Leflunomide in treating rheumatoid arthritis: a double-blind study / 中国新药与临床杂志

treating rheumatoid arthritis.　METHODS: Eighty patients with rheumatoid arthritis were randomly divided into two groups with each group having 40 patients. Group one (M 8, F 32; age 46 a± s 11 a; disease history 63 mo±48 mo) was treated with anti-inflammation sub-group No.1 and No.3. Group two (M 6, F 34; 44 a±9 a; disease history 45 mo±45 mo) was treated with sub-group No.2 and No.4. One week before the initiate of the study, the originally used non-steroid anti-inflammation drugs were stopped for all two-groups patients and each patient took 2 tablets of oxaprozin po qn. At the beginning of the study the patients received 2 tablets of anti-inflammation drugs No.1 daily and 6 tables of No.3 weekly in 1st group, and 2 tablets of anti-inflammation drugs No.2 daily and 6 tablets of No.4 weekly in 2nd group respectively.　RESULTS: In the leflunomide group, the total effect rate was 93 % and the remarkable improvement rate was 85 %. In the methotrexate group, the total effect rate was also 93 % and the remarkable effect rate was 83 %, P>0.05. Nine patients (23 %) in leflunomide group had adverse reaction as mainly skin itch, nettle-like rash, decrease of leukocytes, liver malfunction and others. Seventeen parients (43 %) in methotrexate group had adverse reaction as mainly responses of digestive tract, liver enzyme elevation, decrease of leukocytes, trichomadesis, manoxenia, and others.　CONCLUSION: Leflunomide has similar therapeutic efficacy to methotrexate. However, it has relatively less toxicity.