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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.

Objectives This study aims to determine whether baseline body mass index (BMI) affects clinical response to tocilizumab (TCZ) after six months of treatment in rheumatoid arthritis (RA) patients. Patients and methods In this prospective study, a total of 52 RA patients (10 males, 42 females; mean age 50.6±12.2 years; range, 23 to 73 years) receiving intravenous TCZ were consecutively recruited and followed-up for six months. BMI was calculated before initiation of TCZ treatment. The primary clinical response criterion was clinical disease activity index (CDAI) low disease activity (LDA) and the secondary clinical response criteria included CDAI remission, disease activity score based on 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) LDA, DAS28-ESR remission, European League Against Rheumatism (EULAR) good response, and decreased DAS28-ESR (ΔDAS28-ESR)≥1.2. Results The number of RA patients classified as normal weight, overweight, and obese according to baseline BMI was 38 (73.1%), eight (15.4%), and six (11.5%), respectively. Similar baseline BMI median levels were found between RA patients reaching CDAI LDA and non-LDA: 21.11 (18.94-23.72) versus 20.78 (20.03-22.29) (p=0.98), and non-significant difference in the proportion of responders between normal weight and overweight/obese RA patients was found (p=0.47). No significant difference was found when the secondary clinical response criteria were applied. Conclusion Our study demonstrates that BMI is not associated with clinical response to TCZ among RA patients and TCZ may be used to treat RA patients regardless of BMI levels.

Supplemental Digital Content is available in the text, 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%, χ2 = 8.228, P = 0.008), anti-cyclic citrullinated peptide (CCP) antibody-positivity (66.7% vs. 10.7%, χ2 = 43.897, P

Background Previous reviews of the diagnosis for rheumatoid arthritis (RA) have not compared anti-mutated citrullinated vimentin (MCV) with anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) in respect of sensitivity, specificity and the area under the curve (AUC) against disease controls for differential diagnosis. This meta-analysis aims to evaluate the value of anti-MCV in the diagnosis for RA, the combined sensitivity of anti-MCV and anti-CCP, and certain clinical characteristics related to the performance of anti-MCV. Methods Medline, Embase, Cochrane Library and Web of Science were searched for articles published up to 25 August 2018. A total of 33 studies including 6044 RA patients and 5094 healthy or disease controls achieved inclusive criteria. QUADAS-2 was applied to evaluate the quality of the included studies. The bivariate random effects model was employed in primary data synthesis to evaluate the diagnostic performance. Results The sensitivity of anti-MCV, anti-CCP and RF in RA diagnosis against a disease control group was 0.71, 0.71, 0.77, with the specificity of 0.89, 0.95, 0.73, and the AUC of the SROC of 0.89, 0.95, 0.82, respectively. The predesign of the primary study and diagnostic criteria were statistically significant as sources of heterogeneity. Anti-MCV and anti-CCP tests demonstrated a sensitivity of 0.77 when performed in parallel, with a sensitivity of 0.60 when performed in series; whereas, the combination of anti-MCV and RF presented a sensitivity of 0.64 when used in series. Conclusions Anti-MCV demonstrates comparable diagnostic value to anti-CCP and RF, thus it can be an effective diagnostic marker for RA and may be written into the next authoritative criteria.

To investigate the clinical efficacy and safety of low-dose rituximab (RTX) for patients in primary Sjögren's syndrome (pSS) with thrombocytopenia.Four pSS patients, 2 with refractory thrombocytopenia and 2 with glucocorticoid-dependent thrombocytopenia, were treated with rituximab at 100 mg, intravenous, weekly for a total of two cycles, together with prednisone 1 - 2 mg×kg(-1)×d(-1), and the counts of platelets and B-cells were evaluated.Efficacy of treatment was observed in all patients. The counts of platelets, at (3 - 39) × 10(9)/L baseline, increased in 1 - 2 weeks, and went up to (107 - 241) × 10(9)/L in 3 - 8 weeks. Sustained remission had been achieved for 27 - 52 weeks. The doses of prednisone were tappered to 3.75 - 7.50 mg/day in 12 weeks. One patient who relapsed at the 27th week (platelet count 47 × 10(9)/L), was retreated with 100 mg of RTX and still had good efficacy. The counts of B-cells reduced to (0.007 - 0.010) × 10(9)/L, but they did not achieved the depletion. There were no severe adverse events during RTX therapy.Our study has shown good efficacy and tolerability of low-dose RTX for pSS with thrombocytopenia. Low-dose RTX allows for reduction in corticosteroid doses and B-cells, while large-scale randomized double-blind controlled trials are needed to confirm the results.

To evaluate the efficacy and safety of etanercept 50 mg once-weekly treatment of Chinese patients with active ankylosing spondylitis (AS).Four hundred patients with active AS, enrolled in six medical centers, were randomly divided into either the treatment group or the placebo group in a 3:1 ratio. The total length of the study was 12 weeks. The first 6-week period was a double-blind placebo controlled treatment period and the second 6-week period was an open-labeled treatment period. During the first 6-week period, 300 patients in the treatment group received once-weekly subcutaneous injection of etanercept (50 mg), whereas the 100 patients in the placebo group received placebo injection. During the second 6-week period, patients in both groups received etanercept (50 mg once weekly subcutaneous injection). The primary end point was the percentage of patients achieving the Assessments in Ankylosing Spondylitis (ASAS) 20% response (ASAS 20) at week 6. Other outcome measures included the percentage of patients achieving ASAS 5/6, partial remission and Bath AS disease activity index 50 (BASDAI 50) responses at week 12.A total of 381 patients completed the trial, including 285 patients in the etanercept group and 96 patients in the placebo group. At week 2, the percentage of patients achieving ASAS 20 in the etanercept group was 55.7%, whereas the placebo group was only 17.0% (P0.001). At week 6, 77.5% of patients in the etanercept group achieved ASAS 20 as compared with 32.3% in the placebo group (P0.001). At the end of 12 weeks, the percentage of patients in the etanercept group achieving the ASAS 20 was 89.5%. Improvements of other measures were also significant in the etanercept group. Etanercept was well tolerated and no malignancy and life-threatening events were observed in this study. Most adverse events observed were mild injection-site reactions.Etanercept 50 mg weekly treatment of Chinese patients with active ankylosing spondylitis is convenient, fast-acting, highly effective, and well tolerated.

To investigate the value of metalloproteinase-3 (MMP-3) levels in assessing efficacy of etanercept treatment in patients with ankylosing spondylitis (AS).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.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 (p0.01) with the declining trend of ESR, CRP, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) (all p0.01). Before the etanercept treatment (week 0), serum levels of MMP-3 were correlated with ESR, CRP, BASDAI and BASFI (p0.05). 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 (P0.05), 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).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.

To investigate the efficacy and safety of Infliximab (IFX) plus methotrexate (MTX) combination therapy in patients with rheumatoid arthritis (RA).Prospectively observe refractory RA patients who were treated with combination therapy of MTX and IFX. IFX was infused at the dosage of 3 mg/kg, in week 0, 2, 6, and then every 8 weeks. During treatment, clinical variables, disease activity and adverse effects were evaluated.After treatment, 69.8%, 52.4%, 29.5% and 7.2% RA patients achieved ACR20, ACR50, ACR70 and ACR90 respectively. There were significant statistical differences in the changes of swollen joint counts, tender joint counts, VAS scale, patient' s global assessment, and physician's global assessment before and after therapy.Infliximab plus MTX achieved significant efficacy and safety in refractory RA patients.

To investigate the effects of alendronate (Alen) on the prevention of systemic glucocorticoid-induced osteoporosis in patients with rheumatic diseases.140 patients suffering from rheumatic diseases, including systemic lupus erythematosus, polymyositis, dermatomyositis, and Sjögren's syndrome, with normal bone mineral density (BMD) and treated with oral glucocorticoids were randomly divided into 2 groups: Alen + calcium group (n = 74) receiving Alen 10 mg once a day and castrate D 600 0.6 g once a day for 24 weeks and control group (n = 66) receiving castrate D 600 0.6 g once a day for 24 weeks. The BMD and biomarkers of bone turnover were measured at baseline and 24 weeks after initiating glucocorticoid therapy.After 24 weeks, the BMD values at lumbar spine, femoral neck, major trochanter, and Ward' s triangle increased by 6.1%, 6.3%, 3.3%, and 2.2% respectively compared with those at baseline (all P0.05), however, those of the control group decreased by 8.7%, 9.1%, 7.7%, and 6.4% respectively (P0.01, P0.05), and the BMD levels at lumbar spine and femoral neck 24 weeks later of the Alen + calcium group were both higher than those of the control group (P0.01, P0.05). 24 weeks later the level of urine cross linked N-telopeptides of type I collagen (NTX) of the Alen + calcium group decreased (P0.05), and the blood osteocalcin (BGP) of the Alen + calcium group increased, however, not significantly (P0.05). There were no significant differences in serum AKP and BGP and urine NTX 24 weeks later between these 2 groups.Improving BMD, alendronate plays an important role in the prevention of glucocorticoid-induced osteoporosis. However, calcium treatment alone fails to prevent the loss of bone.

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.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 foror= 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.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 (P0.0001), and the 50 mg/d dose compared to the 25 mg/d dose (P0.05) 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.T-614, a new slow-acting drug, is effective in treatment of rheumatoid arthritis and is well tolerated.

To investigate the expressions of C(4)D(+)CD(25)(+) T cells in the peripheral blood of patients with systemic lupus erythematosus (SLE) and to identify the relationship between the levels of CD(4)(+)CD(25)(+) T cells and the disease activity and progression of SLE.Fifty-three SLE patients were enrolled in the study. Flow-cytometric assay was employed for detection of CD(4)(+)CD(25)(+) T cells and CD(4)(+)CD(25)(bright) T cells were defined according to fluorescence intensity of CD(25) expression exceeding 100. Meanwhile, correlation analysis was performed between their expression and the scores of SLE disease active index (SLEDAI), C(3), dsDNA and antinuclear antibody titles.The levels of peripheral blood CD(4)(+)CD(25)(+) T cells in SLE were (7.84 +/- 1.85)%, which were significantly lower than those in a group of healthy control [(9.18 +/- 2.01)%, P0.05]. The levels of CD(4)(+)CD(25)(+) T cells in a group of active SLE [(6.72 +/- 1.16)%] were higher than those in a group of stable SLE [(8.57 +/- 1.91)%, P0.01]. There was no difference between the active and stable groups of SLE in peripheral blood CD(4)(+)CD(25)(bright) T cells [(0.85 +/- 0.24)% vs (0.91 +/- 0.25)%, P = 0.686], but they were significantly lower than those in the group of healthy controls [(1.43 +/- 1.08)%, P0.01]. With the reduction of the SLEDAI scores in SLE patients after relevant treatment, the levels of peripheral blood CD(4)(+)CD(25)(bright) T cells did not change. No correlation was found between the levels of CD(4)(+)CD(25)(bright) T cells and SLEDAI scores, antinuclear antibody titles, dsDNA and C(3), respectively (rho = -0.188, P = 0.178; rho = -0.216, P = 0.121; rho = 0.082, P = 0.560; rho = 0.010, P = 0.944).The reduction of CD(4)(+)CD(25)(+) T cells in peripheral blood may participate in the pathogenesis of SLE.

To explore the role of several chemokines in rheumatoid arthritis (RA) and their clinical significance.ELISA was used to detect the serum levels of interleukin (IL)-8, interferon-gamma inducible protein (IP)-10, and RANTES in 58 active RA patients, 29 clinically remissive RA patients, 21 osteoarthritis (OA) patients, and 30 healthy volunteers. Clinical data of these patients were compared between different groups.The serum levels of IL-8, IP-10 and RANTES in the active RA patients were significantly higher than those of the healthy controls and OA patients. The serum level of IP-10 of the active patients was higher than that of the clinically remissive patients. The index IL-8/IP-10 x RANTES/IP-10 of the active patients was higher than that of the healthy controls (P = 0.01). The serum RANTES level was positively correlated with erythrocyte sedimentation rate, C-reactive protein, platelet count, and numbers of swollen joints, and was negatively correlated with the hemoglobin level. The serum level of IP-10 was negatively correlated with X-ray image grade of hand and wrist joints.The serum levels of IL-8, IP-10 and RANTES significantly increase in active RA. The level of RANTES may be a useful additional marker for disease activity and the level of IP-10 can be used as an index of prognosis.