Kimihiko Takeuchi

Synovectomy reduces stromal-cell-derived factor-1 (SDF-1) which is involved in the destruction of cartilage in osteoarthritis and rheumatoid arthritis

We have compared the concentrations of stromal-cell-derived factor-1 (SDF-1), matrix metalloproteinase-1 (MMP-1), MMP-9 and MMP-13 in serum before and after synovectomy or total knee replacement (TKR). We confirmed the presence of SDF-1 and its receptor CXCR4 in the synovium and articular cartilage by immunohistochemistry. We established chondrocytes by using mutant CXCR4 to block the release of MMPs. The level of SDF-1 was decreased 5.1- and 6.7-fold in the serum of patients with OA and RA respectively, after synovectomy compared with that before surgery. MMP-9 and MMP-13 were decreased in patients with OA and RA after synovectomy. We detected SDF-1 in the synovium and the bone marrow but not in cartilage. CXCR4 was detected in articular cartilage. SDF-1 increased the release of MMP-9 and MMP-13 from chondrocytes in a dose-dependent manner. The mutant CXCR4 blocked the release of MMP-9 and MMP-13 from chondrocytes by retrovirus vector. Synovectomy is effective in patients with OA or RA because SDF-1, which can regulate the release of MMP-9 and MMP-13 from articular chondrocytes for breakdown of cartilage, is removed by the operation.

The assessment of biologic treatment in patients with rheumatoid arthritis using FDG-PET/CT

OBJECTIVES To evaluate whether there is a correlation between the differences in joint uptake of 2-[18F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) and the improvement of clinical findings in RA patients undergoing anti-TNF therapies. METHODS Twenty-two patients who received anti-TNF therapies, including infliximab for 16 patients and etanercept for 6 patients, were assessed. PET with (18)F-FDG studies and clinical assessments were performed at baseline and 6 months after the initiation of therapy. The maximal standardized uptake value (SUV(max)) was used as a representative value for the assessment of the FDG uptake in the bilateral shoulder, elbow, wrist, hip, knee and ankle joints. Spearmans rank correlation test was applied to assess the correlation between the SUV and the clinical parameters. RESULTS The ΔSUV (12 joints), the difference in the SUV(max) of the affected 12 joints before and after treatment, was positively correlated with the ΔDAS28 (r = 0.609, P = 0.003), ΔDAS28-CRP (r = 0.656, P = 0.001) and Δtender joint count (TJC) (r = 0.609, P = 0.003). There were also significantly positive correlations between ΔSUV (8 joints); the difference in the SUV(max) of the bilateral shoulder, elbow, wrist and knee joints before and after treatment and the ΔDAS28 (r = 0.642, P = 0.001), ΔDAS28-CRP (r = 0.712, P < 0.001) and ΔTJC (r = 0.608, P = 0.003), respectively. CONCLUSION The FDG uptake observed in the inflamed RA joints may reflect disease activity. The FDG-PET response was correlated with the clinical response to the biologic treatment of RA.

Evaluation of hemangioma by positron emission tomography: role in a multimodality approach.

Purpose The relative utility of various preoperative diagnostic imaging modalities for the evaluation of hemangioma of the extremities, including positron emission tomography (PET) (using 18F-fluoro-2-deoxy-D-glucose [FDG] and fluorine-18 alpha-methyltyrosine [FMT]), computed tomography (CT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA), was investigated. Methods Imaging findings in 16 patients with 16 histopathologically documented hemangiomas of the extremities were retrospectively reviewed. Preoperative imaging included: FDG-PET (n = 16), FMT-PET (n = 12), MRI (n =16), CT (n =11), and DSA (n =14). Results All 16 lesions examined by PET with FDG and/or FMT showed accumulation. The standardized uptake values (SUVs) for FDG-PET for the 16 examined tumors ranged from 0.7 to 1.67; for FMT-PET, they ranged from 0.14 to 1.00. The SUVs with both tracers indicated the benign nature of the tumor. Computed tomography demonstrated variable attenuation and phleboliths in two patients. The MRI signal characteristics were relatively consistent: heterogeneous signals were slightly higher than those of skeletal muscle on T1-weighted images and brighter than those of subcutaneous fat on T2-weighted images. The pooling and cotton-wool staining depicted in DSA was found to be significantly correlated with FDG accumulation, suggesting that localized blood retention–induced ischemia may accelerate anaerobic glycolysis, which leads to high FDG uptake. Conclusion Although plain radiography, CT, MRI, and angiography may provide anatomic extent and be pathognomonic, FDG-PET and FMT-PET may be the most reliable among the studied imaging modalities for differentiating benign hemangiomas from other soft tissue tumors, especially malignant neoplasms.

Physical activity of elderly patients with rheumatoid arthritis and healthy individuals: an actigraphy study

BackgroundMost people with rheumatoid arthritis (RA) are physically inactive. An accelerometer worn on the waist has been used to evaluate physical activity in people with chronic conditions. It is useful for evaluating moderate to vigorous activity, although it tends to underestimate light or mild activities such as housework or family duties. An accelerometer worn on the wrist (i.e., actigraph) has recently been used to capture daily physical activity in inactive individuals. The purposes of this study were to investigate physical activity measured by an actigraph in patients with RA and in healthy individuals and to investigate the association between actigraphic data and self-reported physical function.MethodsThe subjects were 20 RA patients and 20 healthy individuals. All participants wore an actigraph on their wrist for 6–7 consecutive days. They also completed the Health Assessment Questionnaire disability index (HAQ-DI) and the Medical Outcomes Study (MOS) 36-item short form health survey (SF-36). We extracted three parameters from the actigraphic data: mean activity count (MAC), peak activity count (PAC), and low activity ratio (LAR). These three parameters were compared between the RA patients and healthy individuals and with the self-reported questionnaires.ResultsThe MAC was significantly lower and the LAR was significantly higher in RA patients than in healthy individuals. The PAC was not different between the two groups. The LAR was negatively correlated with the MAC for the RA patients and for the healthy individuals. The decrease ratio of the LAR with the increase of the MAC for the RA patients was twice that of the healthy participants. In the RA patients, the LAR was significantly and moderately correlated with the HAQ-DI score and two dimensions of the SF-36 (i.e., “physical functioning” and “bodily pain”).ConclusionInvestigation of the proportion of low activity count using an actigraph may be useful to identify characteristics of the physical function in RA patients.

Effects of FR167653, a dual inhibitor of interleukin-1 and tumor necrosis factor, on adjuvant arthritis in rats

Abstract The effects of FR167653, a dual inhibitor of interleukin (IL)-1β and tumor necrosis factor (TNF)-α production, on the development of adjuvant arthritis were investigated in rats. Female Sprague–Dawleys rats weighing 130 g with adjuvant arthritis were administered FR167653 0.1, 1, 10, or 30 mg/kg, and their arthritis scores, soft tissue X-rays, and histological findings were then compared with those of a control group. Body weights were also recorded. FR167653 suppressed the severity of adjuvant arthritis in a dose-dependent manner. Administration of the drug had little effect on body weight. FR167653 might locally affect arthritic joints to prevent inflammation. However, further experiments are necessary to elucidate the underlying mechanisms.

Comparison of golimumab 100-mg monotherapy to golimumab 50 mg plus methotrexate in patients with rheumatoid arthritis: Results from a multicenter, cohort study

Objective. The aim of this study was to compare the efficacy and safety of golimumab (GLM) 50 mg + methotrexate (MTX) combination therapy and GLM 100 mg monotherapy in patients with rheumatoid arthritis (RA). Methods. The subjects were 115 RA patients (92 females and 23 males; median (range) age, 64 (17–87) years; median (range) disease duration, 8 (0.6–48) years) started on GLM. Eighty-three patients received GLM 50 mg/4 weeks + MTX (C group; median (range) MTX dosage 8 (2–16) mg/week), and 32 patients received GLM 100 mg/4 weeks (M group). Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), matrix metalloproteinase-3, disease activity score (DAS) 28-ESR, DAS28-CRP, simplified disease activity index, and clinical disease activity index were evaluated 4, 12, and 24 weeks after starting GLM. Results. There were no significant differences in disease activity, adverse events, and drug continuation rates at 24 weeks between the groups. The DAS28-ESR remission rate was 34% in the C group and 26% in the M group. Conclusions. GLM 100 mg monotherapy improved disease activity as well as GLM 50 mg + MTX combination therapy. GLM 100 mg monotherapy appears to have a sufficient therapeutic effect in RA patients who cannot take MTX.

A case of bilateral rheumatoid pleuritis successfully treated with tocilizumab

Abstract The patient was a 77-year-old woman diagnosed as having rheumatoid arthritis (RA) in 1973. She was initiated on infliximab therapy in addition to methotrexate administration in 2009. The therapeutic response decreased after the fifth dose of infliximab, and the patient developed rheumatoid pleuritis due to increased RA disease activity. The therapy was switched from infliximab to tocilizumab, which resulted in amelioration of the arthralgias well as pleuritis. Our results suggest that tocilizumab is an effective treatment alternative for the treatment of rheumatoid pleuritis.

The three-year efficacy of iguratimod in clinical daily practice in patients with rheumatoid arthritis

Abstract Objectives: To assess the middle-term outcome of iguratimod (IGU) in rheumatoid arthritis (RA) patients. Methods: Sixty-nine RA patients (14 males and 55 females, mean age of 64.0 years) receiving IGU-containing therapies were enrolled. We divided these patients into three groups based on the treatment at the baseline: an IGU group, a methotrexate (MTX) plus IGU group, and a biologics plus IGU group. The baseline characteristics and clinical course were evaluated over three years. Predictive factors associated with the achievement of low disease activity (LDA) were statistically analyzed. Results: The survival rate of IGU therapy at 3 years was 40.6%. The disease activity was significantly decreased in the IGU group and MTX plus IGU group compared with the baseline. Furthermore, 38 patients (55.1%) were in remission or had LDA at 3 years. The patient gender, use of prednisolone (PSL) and DAS28-CRP at baseline were the factors associated with the achievement of remission or LDA at three years. Conclusion: IGU was effective without MTX or bDMARDs as well as in combination with MTX. A female gender, no use of PSL and a low DAS28-CRP at the initiation of IGU were associated with clinical remission or LDA achievement at three years.

THU0191 Comparison of Golimumab 50 Mg/4 Weeks plus Methotrexate with Golimumab 100 Mg/4 Weeks Monotherapy in Patients with Rheumatoid Arthritis: Results from the Japanese GRN Multicenter Cohort Study

Background The treatment of rheumatoid arthritis (RA) has been transformed by the development of novel agents targeting biological factors. The idea of “treat to target” has emerged. Early aggressive treatment with methotrexate (MTX) and tumor necrosis factor inhibitors can lead to clinical, radiological and even functional remission in a large proportion of patients with RA. However, there is a population of patients with RA who cannot be treated with MTX. A few clinical studies have reported the efficacy of GLM 100 mg/4 weeks as monotherapy. However, few papers have so far compared GLM 50 mg/4 weeks plus MTX with GLM 100 mg/4 weeks monotherapy. Objectives The aim of this study was to compare GLM 50 mg/4 weeks plus MTX with GLM 100 mg/4 weeks monotherapy in patients with RA. Methods The subjects were 115 RA patients (92 females; 23 males) who started receiving GLM treatment after September 2011 at Gunma University Hospital and four other institutes (the Gunma Rheumatoid Arthritis Network: GRN). The mean age (range) of the patients was 64 years (17–87), and the mean disease duration was 10 years (0.6–48). Seventy-two of the 114 patients were bio-naïve patients. Eighty-three patients received GLM 50 mg/4 weeks plus MTX (C group) and 32 patients received GLM 100 mg/4 weeks as monotherapy (M group). The mean MTX dosage in the GLM 50 mg/4 weeks plus MTX group was 7.9 mg/week. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, matrix metalloproteinase-3 (MMP-3) level, the swollen and tender joint counts and the disease activity score in 28 joints using the ESR (DAS28-ESR) were examined at baseline and six months later. The remission rate and continuation rates at six months were also examined. Results The age was significantly higher and the disease duration was significant longer in the M group, however, there were no significant differences in the serum markers or disease activity between the groups at baseline. Additionally, there were also no significant differences in the serum markers or disease activity of the two groups at six months after treatment. The DAS28-ESR remission (DAS28-ESR <2.6) rate was 38% in the C group and 21% in the M group. The continuation rate of GLM at six months was 80% in the C group and 84% in the M group. Conclusions In this study, monotherapy improved the disease activity and as well as the combination therapy. These results suggest that GLM 100 mg/4 weeks monotherapy can have a sufficient therapeutic effect in RA patients who cannot use MTX. References Smolen, JS., et al. FGolimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet. 2009. Takeuchi T. et al. Golimumab monotherapy in Japanese patients with active rheumatoid arthritis despite prior treatment with disease-modifying antirheumatic drugs: results of the phase 2/3, multicentre, randomised, double-blind, placebo-controlled GO-MONO study through 24 weeks. Ann Rheum Dis. 2013. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4102

SAT0419 Comparison of 18FDG-PET and MRI of the shoulder in patients with rheumatoid arthritis

Background Rheumatic diseases including rheumatoid arthritis (RA) have been investigated using 18FDG-PET (PET). A relationship has been identified among the disease activity, the progress of the joint destruction and the PET findings. In addition, there have so far been few reports about the relationship between PET and synovitis in magnetic resonance imaging (MRI) of the wrist and knee. However, the relationship between synovitis in MRI and the uptake in PET of the shoulder joints is unclear, as is the cut-off line of the standardized uptake value (SUV). Objectives The aim of this study is to assess the PET findings and synovitis of the shoulder joints in the MRI findings in RA patients. Methods Forty-three shoulders in 42 patients with RA were assessed with PET and MRI. The mean age (range) was 54 years (36–75) and the mean disease duration was 9 years (1–40). 18F-FDG uptake was quantified using the maximum pixel value of the SUV. Synovitis in shoulder MRIs was examined in the axillary pouch (AP), subacromial bursa (SAB), subdeltoid bursa (SDB), rotator interval (RI) and acromioclavicular joint (ACJ). The relationships between synovitis and SUV were examined. Results The mean PET SUVmax (range) was 1.99 (0.87-6.17). MRI showed that 8 of 43 shoulders had synovitis in the AP, 17 in the SAB, 12 in the SDB, 16 in the RI and 5 in the ACJ. The total number of synovitis sites was significantly correlated with the SUV (R=0.72, P<0.01). The area under an ROC curve was 0.88. The sensitivity was 0.833 and specificity was 0.842 with a SUV cut-off line of 1.50. Conclusions The SUV of the PET reflected synovitis of the shoulder MRI in patients with RA. The cut-off level of the SUV was 1.50 in an RA shoulder joint. References Polisson RP, Schoenberg OI, Fischman A, Rubin R, Simon LS, Rosenthal D, Palmer WE. Use of magnetic resonance imaging and positron emission tomography in the assessment of synovial volume and glucose metabolism in patients with rheumatoid arthritis. Arthritis Rheum 1995; 38(6): 819-825 Palmer WE, Rosenthal DI, Schoenberg OI, et al. Quantification of inflammation in the Wrist with Gadolium-enhansed MR Imaging and PET with 2-IF-181-Fluoro2-deoxy-D-glucose. Radiology 1995; 196: 647. Beckers C, Jeukens X, Ribbens C, André B, Marcelis S, Leclercq P, Kaiser MJ,Foidart J, Hustinx R, Malaise MG. (18)F-FDG PET imaging of rheumatoid knee synovitis correlates with dynamic magnetic resonance and sonographic assessments as well as with the serum level of metalloproteinase-3. Eur J Nucl Med Mol Imaging 2006; 33(3):275-280 Disclosure of Interest None Declared