A double-blind, double-dummy, randomized controlled, multicenter trial of 99Tc-methylene diphosphonate in patients with moderate to severe rheumatoid arthritis / 中华医学杂志(英文版)

BACKGROUND@#Clinical observational studies revealed that 99Tc-methylene diphosphonate (99Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of 99Tc-MDP plus methotrexate (MTX) vs. MTX alone or 99Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA.@*METHODS@#Eligible patients with moderate to severely active RA were randomized to receive 99Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or 99Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48.@*RESULTS@#At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + 99Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or 99Tc-MDP group (47.5%) (P = 0.03 for MTX + 99Tc-MDP vs. MTX, and MTX + 99Tc-MDP vs.99Tc-MDP, respectively). The participants in the MTX + 99Tc-MDP group and the 99Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + 99Tc-MDP vs. MTX: P = 0.03, 99Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed.@*CONCLUSIONS@#This study demonstrated that the combination of 99Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and 99Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of 99Tc-MDP therapy in patients with RA are warranted.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.

Anti-cyclic citrullinated peptide antibody predicts the development of rheumatoid arthritis in patients with undifferentiated arthritis / 中华医学杂志(英文版)

BACKGROUND@#Clinical outcomes of undifferentiated arthritis (UA) are diverse, and only 40% of patients with UA develop rheumatoid arthritis (RA) after 3 years. Discovering predictive markers at disease onset for further intervention is critical. Therefore, our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.@*METHODS@#We performed a prospective, multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals. Clinical and serological parameters were obtained at recruitment. Follow-up was undertaken in all patients every 12 weeks for 2 years. Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.@*RESULTS@#A total of 234 patients were recruited in this study, and 17 (7.3%) patients failed to follow up during the study. Among the 217 patients who completed the study, 83 (38.2%) patients went into remission. UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9% vs. 16.8%, χ = 8.228, P = 0.008), anti-cyclic citrullinated peptide (CCP) antibody-positivity (66.7% vs. 10.7%, χ = 43.897, P < 0.001), and double-positivity rate of RF and anti-CCP antibody (38.1% vs. 4.1%, χ = 32.131, P < 0.001) than those who did not. Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017, 95% confidence interval: 5.803-55.938; P < 0.001).@*CONCLUSION@#As an independent predictor of RA, anti-CCP antibody should be tested at disease onset in all patients with UA.

Serum metalloproteinase-3 levels in assessing efficacy of Etanercept in patients with ankylosing spondylitis / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the value of metalloproteinase-3 (MMP-3) levels in assessing efficacy of etanercept treatment in patients with ankylosing spondylitis (AS).</p><p><b>METHODS</b>The serum and synovial fluid levels of MMP-3 were measured by enzyme linked immunosorbent assay (ELISA) in 48 patients with AS in week 0, 6 and 12; and also measured in 30 serum samples and 10 synovial fluid samples from healthy controls.</p><p><b>RESULTS</b>The serum levels of MMP-3 in AS patients were significantly higher than those in controls. In AS patients, the MMP-3 levels in synovial fluid were significantly higher than those in serum levels. The serum MMP-3 levels in AS patients with peripheral arthritis were higher than those with exclusively axial involvement; while C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) did not differ between these 2 groups of AS. At week 6 and week 12 of etanercept treatment, the serum MMP-3 levels were significantly decreased (p<0.01) with the declining trend of ESR, CRP, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) (all p<0.01). Before the etanercept treatment (week 0), serum levels of MMP-3 were correlated with ESR, CRP, BASDAI and BASFI (p<0.05). ESR was also correlated with CRP and BASFI, but not with BASDAI (r=0.361, P=0.071). At weeks 12, serum MMP-3 levels were still correlated with ESR, CRP and BASDAI (P<0.05), but not with BASFI (P=0.339); ESR was correlated with CRP, but not with BASDAI and BASFI. There was a significant correlation between BASDAI and BASFI (r=0.818,P=0.001).</p><p><b>CONCLUSION</b>Serum MMP-3 levels are closely related to disease activity and may serve as an useful indicator for efficacy of etanercept treatment in AS patients.</p>

Safety and efficacy of T-614 in the treatment of patients with active rheumatoid arthritis: a double blind, randomized, placebo-controlled and multicenter trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A novel anti-rheumatic drug, T-614, has been shown to have an anti-inflammatory effect and to improve abnormal immunological findings in rheumatoid arthritis (RA). To assess the safety and efficacy of T-614 versus placebo in patients with active RA we conducted a 24-week clinical study in 280 Chinese patients.</p><p><b>METHODS</b>In a multicenter, randomized, double blind, placebo controlled study, 280 patients were randomly assigned to receive placebo (n = 95) or T-614 at 50 mg (n = 93) or 25 mg (n = 92) daily. Active disease was defined by 4 of the following 5 criteria: >or= 5 tender joints, >or= 3 swollen joints, morning stiffness lasting for >or= 60 minutes, and Westergren erythrocyte sedimentation rate (ESR) >or= 28 mm/h, the assessment of pain at the rest by patient as moderate or severe. Clinical and laboratory parameters were analyzed at baseline, 2, 4, 6, 12, 18 and 24 weeks. The primary efficacy variable at week 24 was the American College of Rheumatology (ACR) response rate using the intent-to-treat population.</p><p><b>RESULTS</b>The ACR response rate was significantly higher in the T-614 treatment group compared with the placebo group within 8 weeks after the initiation of treatment. After 24 weeks, the 25 mg/d and 50 mg/d dosage groups and the placebo group showed 39.13%, 61.29% and 24.21% in ACR20 and 23.91%, 31.18% and 7.37% in ACR50, respectively. A time-response in ACR response was observed, with clear superiority for the 25 mg/d and 50 mg/d dosage groups compared to placebo (P < 0.0001), and the 50 mg/d dose compared to the 25 mg/d dose (P < 0.05) when using the ACR response analyses after 24 weeks. ESR and c-reactive protein (CRP) were significantly different in the treatment groups after 24 weeks. The incidence of adverse events (AEs) was not significantly higher with T-614 than with placebo, but upper abdominal discomfort, leucopenia, elevated serum alanine aminotransferase (sALT), skin rash and/or pruritus were more common in the 50 mg and 25 mg dosage groups.</p><p><b>CONCLUSION</b>T-614, a new slow-acting drug, is effective in treatment of rheumatoid arthritis and is well tolerated.</p>

Treatment of rheumatoid arthritis with T-614:a multicenter,randomized,double blind,placebo-controlled trial / 中华风湿病学杂志

Objective To study the efficacy and safety of T-614 in treating rheumatoid arthritis(RA). Methods Two hundred and eighty patients with active RA were randomly allocated to 3 groups:T-614 50 mg each day,25 mg each day or placebo.Clinical and laboratory parameters were analyzed at baseline,2,4,6,12, 18 and 24 weeks.Results The ACR response rate was significantly higher in the T-614 treatment group com- pared with the placebo group during the first 6 weeks.After 24 weeks,25 mg/d,50 mg/d dosage group and the placebo group showed 39.1%,61.3% and 24.2% in ACR20,23.9%,31.2% and 7.4% in ACR50 respectively.A time-response in ACR response after 24 weeks was observed,with clear superiority of the 25 mg/d and 50 mg/d dosage groups compared to the placebo,and 50 mg/d dosage group compared to 25 mg/d dosage group(P