Meta-analysis: compared with anti-CCP and rheumatoid factor, could anti-MCV be the next biomarker in the rheumatoid arthritis classification criteria?

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.

[The efficacy and safety of low-dose rituximab in treatment of primary Sjögren's syndrome with thrombocytopenia].

OBJECTIVE: To investigate the clinical efficacy and safety of low-dose rituximab (RTX) for patients in primary Sjögren's syndrome (pSS) with thrombocytopenia. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[A multicenter, double-blind, randomized, placebo-controlled clinical trial of etanercept treatment of Chinese patients with active ankylosing spondylitis].

OBJECTIVE: To evaluate the efficacy and safety of etanercept 50 mg once-weekly treatment of Chinese patients with active ankylosing spondylitis (AS). METHODS: 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. RESULTS: 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% (P < 0.001). At week 6, 77.5% of patients in the etanercept group achieved ASAS 20 as compared with 32.3% in the placebo group (P < 0.001). 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. CONCLUSION: Etanercept 50 mg weekly treatment of Chinese patients with active ankylosing spondylitis is convenient, fast-acting, highly effective, and well tolerated.

A double-blind, double-dummy, randomized controlled, multicenter trial of 99Tc-methylene diphosphonate in patients with moderate to severe rheumatoid arthritis.

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.

[Serum metalloproteinase-3 levels in assessing efficacy of Etanercept in patients with ankylosing spondylitis].

OBJECTIVE: To investigate the value of metalloproteinase-3 (MMP-3) levels in assessing efficacy of etanercept treatment in patients with ankylosing spondylitis (AS). METHODS: 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. RESULTS: 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). CONCLUSION: 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.

[Efficacy and safety of infliximab in patients with rheumatoid arthritis].

OBJECTIVE: To investigate the efficacy and safety of Infliximab (IFX) plus methotrexate (MTX) combination therapy in patients with rheumatoid arthritis (RA). METHODS: 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. RESULTS: 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. CONCLUSION: Infliximab plus MTX achieved significant efficacy and safety in refractory RA patients.

Relationship between urate within tophus and bone erosion according to the anatomic location of urate deposition in gout: A quantitative analysis using dual-energy CT volume measurements.

The aim of this study was to measure the urate volume within tophus and bone erosion volume using dual-energy computed tomography in patients with tophaceous gout. Furthermore, our study aims to quantitatively analyze the relationship between monosodium urate (MSU) crystal deposition and bone erosion according to the anatomic location of urate deposition.Seventy-seven subjects with chronic gout were positively identified for the presence of urate deposition. Only 27 subjects identified for the presence of urate in contact with bone erosion were included in this study. The urate volumes and associated erosion volumes were measured. The relationships between urate within tophus and bone erosion were separately analyzed according to the anatomic location of urate deposition.Twenty-seven subjects were all male (100%) with a median (interquartile range, IQR) age of 52 (45-61) years. From all the subjects, 103 tophi depositions were identified in contact with bone erosion, including 58/103 tophi that contained an intraosseous component and 45/103 nonintraosseous tophi. Tophi containing intraosseous components were larger than nonintraosseous tophi (urate volume: median [IQR] 45.64 [4.79-250.89] mm vs 19.32 [6.97-46.71] mm, P = .035) and caused greater bone erosion (erosion volume: 249.03 [147.08-845.33] mm vs 69.07 [32.88-111.24] mm, P < .001). Almost all erosion volumes were larger than urate volumes in nonperiarticular tophi, in contrast to most erosion volumes, which were less than urate volumes in the tophi that contained a periarticular component (odds ratio, 95% confidence interval: 74.00, 14.70-372.60; P < .001). Urate volume and erosion volume demonstrated positive correlations in intraosseous tophi, intraosseous-intra-articular-periarticular tophi, and intraosseous-intra-articular tophi (rs = 0.761, rs = 0.695, rs = 0.629, respectively, P < .05).MSU crystal deposition shows a promoting effect on the development of bone erosions in varying degrees, associated with the location of MSU crystals deposited in the joints. The intraosseous tophi contribute the most to bone erosions, followed by intra-articular tophi, and periarticular tophi.

Body Mass Index and Clinical Response to Tocilizumab in Patients With Rheumatoid Arthritis.

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.

Anti-cyclic citrullinated peptide antibody predicts the development of rheumatoid arthritis in patients with undifferentiated arthritis.

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.

Safety and efficacy of T-614 in the treatment of patients with active rheumatoid arthritis: a double blind, randomized, placebo-controlled and multicenter trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: T-614, a new slow-acting drug, is effective in treatment of rheumatoid arthritis and is well tolerated.

[Alendronate prevents steroid-induced osteoporosis in patients with rheumatic diseases].

OBJECTIVE: To investigate the effects of alendronate (Alen) on the prevention of systemic glucocorticoid-induced osteoporosis in patients with rheumatic diseases. METHODS: 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. RESULTS: 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 P<0.05), however, those of the control group decreased by 8.7%, 9.1%, 7.7%, and 6.4% respectively (P<0.01, P<0.05), 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 (P<0.01, P<0.05). 24 weeks later the level of urine cross linked N-telopeptides of type I collagen (NTX) of the Alen + calcium group decreased (P<0.05), and the blood osteocalcin (BGP) of the Alen + calcium group increased, however, not significantly (P>0.05). There were no significant differences in serum AKP and BGP and urine NTX 24 weeks later between these 2 groups. CONCLUSION: 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 randomized, controlled trial of efficacy and safety of Anbainuo, a bio-similar etanercept, for moderate to severe rheumatoid arthritis inadequately responding to methotrexate.

The objective of the study was to evaluate the efficacy and safety of etanercept (Anbainuo) treatment in Chinese moderate to severe rheumatoid arthritis (RA) with inadequate response to methotrexate (MTX-IR); 600 patients (360 in phase III-1 and 240 in phase III-2) poorly responding to MTX were enrolled in the study and randomized at a ratio of 2:1 into an Anbainuo treatment or control group. The study was designed as a 12-week double-blind, placebo-controlled period followed by a 12-week open-label study. The primary endpoint was the ACR20 response rate at week 12. Secondary endpoints included the ACR50, ACR70, ACR-N, and safety. At week 12, ACR20 response was observed in 60.9 % of the Anbainuo group-significantly higher than that of the control group (20.6 %). At week 24, the ACR20 response in the Anbainuo group increased to 70.2 %; there was no significant difference compared with that of the control group (61.8 %, P > 0.05). At week 12, the ACR50 and ACR70 responses of the Anbainuo group increased to 25.6 and 6.8 %, compared to 4 and 1 % in the control group (P < 0.001, P = 0.002). The ACR-N was 2.85 ± 6.73 vs. -3.24 ± 8.78 % in the control group (P < 0.001). During the first 12 weeks of treatment, 66 adverse events (AE) were reported in the Anbainuo group (15.6 %) and 21 AEs (10.5 %) occurred in the control group, whereby the rate of the Anbainuo group was slightly higher than the control group (P = 0.042). Severe adverse events (SAEs) occurred in the Anbainuo group (1.3 %) and one (SAE) occurred in the control group (0.5 %) (P = 0.19). Anbainuo displays a rapid onset of efficacy as well as good tolerance and safety in MTX-IR patients having moderate to severe RA.

[Clinical significance of CD4+CD25+ T cells in peripheral blood of patients in systemic lupus erythematosus].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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)%, P < 0.05]. 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)%, P < 0.01]. 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)%, P < 0.01]. 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). CONCLUSION: The reduction of CD(4)(+)CD(25)(+) T cells in peripheral blood may participate in the pathogenesis of SLE.

[Serum levels of several chemokines in patients with rheumatoid arthritis].

OBJECTIVE: To explore the role of several chemokines in rheumatoid arthritis (RA) and their clinical significance. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Methods of assessment of tophus and bone erosions in gout using dual-energy CT: reproducibility analysis.

This study aims to evaluate the intraobserver and interobserver reproducibility of the tophus urate volume, erosion volume, and the erosion score measurements in patients with gout by using dual-energy CT (DECT) scans comparing their bone erosion volumes against bone erosion scores and also to determine a valid measure of joint destruction in chronic gout. Sixty-six subjects underwent DECT scans of the hands or feet. Two independent observers measured the tophus urate volumes and bone erosion volumes using automated volume assessment software and the erosion scores based on the rheumatoid arthritis magnetic resonance imaging score (RAMRIS). The intraobserver and interobserver reproducibility were analyzed by intraclass correlation coefficient (ICC) and limits of agreements analysis. The relationship between erosion volumes and erosion scores was analyzed. The intraobserver and interobserver ICC for tophus urate volume measurements (n = 636) were 1.000 (95 % confidence interval (95 % CI) 1.000 to 1.000) and 1.000 (95 % CI 1.000 to 1.000), 0.999 (0.999, 0.999) and 0.999 (0.999, 0.999) for bone erosion volumes (n = 350), 0.937 (0.928, 0.946) and 0.899 (0.883, 0.912) for erosion scores (n = 350). Strong positive correlations were demonstrated between individual erosion volumes and scores (r s = 0.914, p < 0.001) as well as total erosion volume and score per patient (r = 0.838-0.867, p < 0.001). This study demonstrated a high reproducibility of tophus urate volumes, erosion volumes, and erosion score measurements using DECT. Erosion volumes show to be a more direct and accurate method to evaluate bone erosion compared with erosion score, strongly supporting it as a superior and standard measure of structural joint damage in gout.

A multicenter, randomized, double-blind clinical trial of combination therapy with Anbainuo, a novel recombinant human TNFRII:Fc fusion protein, plus methotrexate versus methotrexate alone or Anbainuo alone in Chinese patients with moderate to severe rheumatoid arthritis.

This study aims to evaluate the clinical and radiological efficacy as well as safety profiles of Anbainuo, a recombinant human TNFRII:Fc fusion protein, combined with methotrexate (MTX) versus MTX alone or Anbainuo alone in the treatment of Chinese patients with moderate to severe rheumatoid arthritis (RA). In this 24-week, multicenter, double-blind, active comparator-controlled study, 396 RA patients were randomized into combination therapy group (Anbainuo plus MTX), Anbainuo group, or MTX group. Clinical response was assessed using the American College of Rheumatology (ACR)-N, ACR20, ACR50, ACR70, and van der Heijde modification of Sharp score, among which ACR-N and ACR20 were defined as primary major endpoints. After 24 weeks of treatment, the ACR-N in the combination therapy group (12.79 ± 9.24 %) was significantly higher than that in Anbainuo group (9.56 ± 11.16 %) and in MTX group (5.08 ± 11.1 %) (p = 0.00 and p = 0.00, respectively). Patients in Anbainuo group had significantly higher ACR-N than those in MTX group (p = 0.02). More patients in the combination therapy group (53.6 %) achieved ACR50 improvement response than those in the MTX group (30.8 %). ACR70 of combination therapy group (27.7 %) was significantly higher than that of Anbainuo group (15.8 %) and MTX group (7.70 %), with no significant difference between Anbainuo group and MTX group. DAS28-ESR in the combination therapy group was significantly reduced compared to either monotherapy groups. Moreover, DAS28-ESR was significantly lower in Anbainou group than in MTX group. The combination therapy group also showed significantly less radiographic progression than the MTX group (p = 0.03). The total adverse events (AE) in the combination group (40.9 %) was significantly higher than those in the MTX group (28.8 %) (p < 0.05). Anbainuo combined with MTX therapy can effectively control the disease activity and radiographic progression of RA, while the incidence of AE also increased compared to either Anbainuo or MTX.

Multicenter, randomized, double-blind, controlled trial of treatment of active rheumatoid arthritis with T-614 compared with methotrexate.

OBJECTIVE: To assess the efficacy and safety of T-614 versus methotrexate (MTX) in patients with active rheumatoid arthritis (RA). METHODS: In this multicenter, double-blind trial, 489 patients randomly received either T-614 25 mg/day for the first 4 weeks and 50 mg/day for the subsequent 20 weeks (group 1, n = 163), T-614 50 mg/day for 24 weeks (group 2, n = 163), or MTX 10 mg/week for the first 4 weeks and 15 mg/week for the subsequent 20 weeks (n = 163). Clinical and laboratory parameters were analyzed at baseline and at 4, 10, 17, and 24 weeks. RESULTS: After 24 weeks of treatment, the American College of Rheumatology 20% improvement criteria response rate for patients in T-614 group 2 (63.8%) was not statistically significantly different from that for patients receiving MTX treatment (62.0%), and was superior to that for patients in T-614 group 1 (50.9%). The result of the noninferiority analysis indicated that the efficacy of T-614 (50 mg/day) was not lower than that of MTX by <10%. Rheumatoid factor and IgA, IgG, and IgM demonstrated a statistically significant decrease in all groups. Frequently reported adverse events included hematologic disorder, skin reactions, gastrointestinal symptoms, and transient liver enzyme elevations in the T-614 therapy groups. Side effects in the T-614 groups were generally fewer and milder than in the MTX group, except for skin reactions. There were no prominent cardiovascular adverse events and gastrointestinal ulcers found in the T-614 groups. CONCLUSION: Results indicate that T-614 therapy 50 mg/day is effective and well tolerated, and represents a new option for the treatment of patients with active RA.