Atsushi Ogata

Osaka University, Suika, Ōsaka, Japan

Are you Atsushi Ogata?

Claim your profile

Publications (103)342.11 Total impact

  • Source
  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):1062.1-1062. DOI:10.1136/annrheumdis-2015-eular.5386 · 10.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tocilizumab (TCZ) is a humanized monoclonal antibody against the IL-6 receptor that is indicated for the treatment of rheumatoid arthritis (RA), juvenile idiopathic arthritis and Castleman's disease. TCZ was developed as an intravenous (IV) formulation and approved for RA treatment in Japan (2008), the EU (2009) and the USA (2010). Recently, a subcutaneous (SC) formulation of TCZ was developed and approved for RA treatment. Efficacy and safety of TCZ-SC were reported through three randomized trials: MUSASHI, SUMMACTA and BREVACTA. Clinical efficacy and overall safety of TCZ-SC was comparable to that of TCZ-IV. However TCZ-SC, which is provided in a fixed dose, the efficacy was affected by patient weight. The frequencies of injection site reactions and anti-TCZ antibodies were increased with TCZ-SC compared with TCZ-IV, although differences were minimal and at a negligible level for daily clinical practice. This review highlights the potential of TCZ-SC in RA treatment.
    Therapeutic delivery 04/2015; 6(3):283-95. DOI:10.4155/tde.14.118
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective To investigate whether leucine-rich alpha-2 glycoprotein (LRG) could be a disease activity biomarker of rheumatoid arthritis (RA) during IL-6 blockade.Methods Serum LRG levels in RA patients treated with tocilizumab for 24 weeks (n=59) were determined by ELISA. RA disease activity was evaluated by the Clinical Disease Activity Index (CDAI). Receiver operating characteristics (ROC) curve analysis was used to examine diagnostic performance of LRG and other biomarkers. Monkeys with experimental autoimmune arthritis were treated by anti-IL-6 receptor antibody and their swollen joint counts, joint pathological changes, and blood levels of CRP and LRG were evaluated.ResultsAmong tocilizumab-treated RA patients, patients with active disease (CDAI > 2.8) had significantly high serum LRG levels compared to those in remission. ROC curve analysis suggests that LRG is more useful than CRP, ESR or MMP-3 in discriminating between CDAI remission and active disease during therapy with tocilizumab. In arthritic monkeys with IL-6 blockade, LRG levels correlated with joint scores better than CRP. Histological analysis of joints revealed that LRG levels correlated significantly with granulomatous tissue formation, cartilage degeneration and bone destruction in CRP-low monkeys during IL-6 blockade.Conclusion Under IL-6 inhibition, LRG was more useful than other biomarkers for discriminating active disease in human RA and detecting joint inflammation in arthritic animals. LRG may serve as a convenient biomarker for RA during IL-6 blockade. This article is protected by copyright. All rights reserved.
    Arthritis and Rheumatology 04/2015; 67(8). DOI:10.1002/art.39164
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the longterm safety and efficacy of subcutaneous tocilizumab (TCZ-SC) as monotherapy in patients with rheumatoid arthritis (RA). Of 346 patients who received 24 weeks of double-blind treatment with either TCZ-SC monotherapy, 162 mg every 2 weeks (q2w); or intravenous TCZ (TCZ-IV) monotherapy, 8 mg/kg every 4 weeks; 319 patients continued to receive TCZ-SC q2w in the 84-week open-label extension (OLE) of the MUSASHI study (JAPICCTI-101117). Efficacy, safety, and immunogenicity were evaluated for all patients treated with TCZ during 108 weeks. The proportions of patients who achieved American College of Rheumatology 20/50/70 responses, low disease activity [28-joint Disease Activity Score (DAS28) ≤ 3.2], or remission (DAS28 < 2.6) at Week 24 were maintained until Week 108. The incidences of adverse events and serious adverse events were 498.3 and 16.9 per 100 patient-years (PY), respectively. The overall safety of TCZ-SC monotherapy was similar to that of TCZ-IV monotherapy. Rates of injection site reactions (ISR) through 108 weeks remained similar to rates through 24 weeks. ISR were mild and did not cause any patient withdrawals. No serious hypersensitivity events (including anaphylactic reactions) occurred. Anti-TCZ antibodies were present in 2.1% of patients treated with TCZ-SC monotherapy. TCZ-SC monotherapy maintained a favorable safety profile and consistent efficacy throughout the 108-week study. Like TCZ-IV, TCZ-SC could provide an additional treatment option for patients with RA.
    The Journal of Rheumatology 04/2015; 42(5). DOI:10.3899/jrheum.140665 · 3.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the efficacy and safety of switching from intravenous (IV) tocilizumab (TCZ) to subcutaneous (SC) TCZ monotherapy in rheumatoid arthritis patients. Patients who had completed 24 weeks' TCZ-SC (162 mg/2 weeks) or TCZ-IV (8 mg/kg/4 weeks) monotherapy in the MUSASHI study double-blind period were enrolled in an 84-week open-label extension period (OLE). All received TCZ-SC (162 mg/2 weeks) monotherapy. Effects of the IV-to-SC switch were evaluated at week 36 (12 weeks after switching). Overall, 319 patients received at least one dose of TCZ-SC during OLE; 160 switched from TCZ-IV to TCZ-SC (TCZ IV/SC) and 159 continued TCZ-SC (TCZ SC/SC). DAS28-ESR clinical remission rates were 62.5% (100/160) for TCZ IV/SC and 50.0% (79/158) for TCZ SC/SC at week 24, and were maintained at 62.5% (100/160) and 57.0% (90/158), respectively, at week 36. In the TCZ IV/SC group, 9% (9/100) of patients who had achieved remission at week 24 could not maintain remission at week 36. In TCZ IV/SC patients weighing ≥ 70 kg, the percentage with sufficient serum TCZ concentration (≥1 μg/mL) decreased from 90.9% (10/11) at week 24 to 45.5% (5/11) at week 36. Overall safety profiles were similar in TCZ IV/SC and TCZ SC/SC except for mild injection site reactions in TCZ IV/SC. Efficacy is adequately maintained in most patients switching from TCZ-IV (8 mg/kg/4 weeks) to TCZ-SC (162 mg/2 weeks) monotherapy. Patients receiving TCZ-IV can switch to TCZ-SC without serious safety concerns. Clinical efficacy may be reduced after switching in some high-body-weight patients. This article is protected by copyright. All rights reserved. © 2015 American College of Rheumatology.
    04/2015; DOI:10.1002/acr.22598
  • [Show abstract] [Hide abstract]
    ABSTRACT: To examine whether or not earlier therapeutic intervention with methotrexate (MTX) prevents the development of rheumatoid arthritis (RA) in patients with recent-onset undifferentiated arthritis (UA) showing high anti-citrullinated peptide antibody (ACPA) titers. The patients were divided into two groups, one is treated with MTX (MTX+ group, n = 29), and the other is without MTX (MTX- group, n =19), and other disease-modifying anti-rheumatic drugs were not permitted in two groups before the primary endpoint was met. The primary endpoint is the occurrence of definite RA, and it was compared in two groups after one year. The percentage of patients who developed definite RA in the MTX+ group (17.2%) was significantly lower than that in the MTX- group (78.9%) (log-rank test, P < 0.001, n = 48); adjusted HR 0.028 [95% CI 0.003 to 0.250, P = 0.001, n = 39]. Treatment effectiveness was not decreased by major risk factors of RA onset such as smoking habits or HLA-DRB1 shared epitope (SE) (smoking habit, OR 0.041 [95% CI 0.007 to 0.246] P < 0.001; SE, OR 0.022 [95% CI 0.002 to 0.204] P < 0.001). The safety issues were comparable between the two groups. This suggests that early therapeutic intervention with MTX could safely prevent the development of RA in patients with recent-onset UA showing high ACPA titers.
    Modern Rheumatology 03/2015; DOI:10.3109/14397595.2015.1031364 · 2.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective. Semaphorin 4D (Sema4D) /CD100 plays pleiotropic roles in immune activation, angiogenesis, bone metabolism, and neural development. This study investigated the role of Sema4D in rheumatoid arthritis (RA). Methods. Soluble Sema4D (sSema4D) levels in the sera and synovial fluid were analyzed by ELISA. Cell-surface expression and transcripts of Sema4D were analyzed in peripheral blood cells of RA patients, and immunohistochemical staining of Sema4D was performed in RA synovium. Generation of sSema4D was evaluated in the ADAMTS4-treated monocytic cell line THP-1. The efficacy of anti-Sema4D antibody was evaluated in mouse collagen-induced arthritis (CIA). Results. Levels of sSema4D were elevated in both sera and synovial fluid of RA patients, and disease activities were correlated with serum levels of sSema4D. Sema4D-expressing cells also accumulated in RA synovium. The cell-surface levels of Sema4D on CD3(+) and CD14(+) cells from RA patients were reduced, although the levels of Sema4D-transcripts were unchanged. In addition, ADAMTS4 cleaved cell-surface Sema4D to generate sSema4D in THP-1 cells. sSema4D induced tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) production from CD14(+) monocytes. IL-6 and TNF-α induced ADAMTS4 expression in synovial cells. Treatment with an anti-Sema4D antibody suppressed arthritis and reduced proinflammatory cytokine production in CIA. Conclusions. A positive-feedback loop involving sSema4D/IL-6 and TNF-α/ADAMTS4 may contribute to the pathogenesis of RA. The inhibition of arthritis by anti-Sema4D antibody suggests that Sema4D represents a potential therapeutic target for RA. This article is protected by copyright. All rights reserved. Copyright © 2015 American College of Rheumatology.
    Arthritis and Rheumatology 02/2015; 67(6). DOI:10.1002/art.39086
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background C-reactive protein (CRP) is frequently used to evaluate inflammation in patients with rheumatoid arthritis (RA). However, CRP is normalized when IL-6 function is potently suppressed by anti-cytokine biologics such as tocilizumab. Therefore, novel biomarkers are required for accurate and sensitive assessment of the inflammation during anti-cytokine therapy. By proteomic screening of sera from patients with rheumatoid arthritis (RA), we previously identified serum leucine-rich alpha-2 glycoprotein (LRG) as a potential biomarker that reflects disease activity in RA better than CRP. Objectives This study is aimed to investigate the clinical significance of LRG as a biomarker of RA disease activity during anti-IL-6 therapy. Methods As a preclinical testing, cynomolgus monkeys with collagen induced arthritis (CIA) were treated with anti-IL-6 receptor antibody (anti-IL-6R mAb) and joint swelling and rigidity were scored for clinical assessment of arthritis throughout the experiment. At the time of sacrifice, blood samples were collected to be subjected to the measurement of LRG and CRP. RA patients treated with tocilizumab were enrolled and clinical disease activity index (CDAI) and serum levels of LRG and CRP were evaluated. Results In CIA monkeys with anti-IL-6R mAb treatment, plasma LRG levels correlated better with disease activity than plasma CRP levels, presumably due to the fact that LRG levels were elevated in some animals with negative CRP in spite of high arthritis scores. Furthermore, among tocilizumab-treated patients for 6 months with normalized CRP levels (<0.2 mg/dL), serum LRG levels were significantly higher in patients with active RA (defined by CDAI>10) than those with RA with low disease activity (CDAI≤10). Conclusions Our study indicates that LRG is a promising biomarker for monitoring disease activity in RA, even when CRP levels are reduced or normalized by anti-cytokine therapy. References Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2180
    Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):852-852. DOI:10.1136/annrheumdis-2014-eular.2180 · 10.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Rheumatoid arthritis (RA) is an autoimmune and inflammatory disorder of joints, which characterized with periarticular bone resorption. Recently cross-disciplinary field osteoimmunology was established because of reciprocal interactions between the immune and skeletal systems. To date, it is well known that inflammatory cytokines such as IL-6 and TNF stimulate bone resorption directly or through RANKL pathway. Recently semaphorins are thought to be new players in osteoimmunology. Sema4D that is produced by osteoclasts inhibits osteoblastgenesis and Sema3A that is produced by osteoblasts inhibits osteoclastgenesis. We previously reported Sema4D activate not only B cells, but also macrophage/monocytes, and induce proinflammatory cytokine production. These findings suggest that Sema4D plays an important role in the pathogenesis of RA and become a promising therapeutic target of RA. Objectives To investigate the role of Sema4D in RA patients. Methods The soluble Sema4D levels in sera and synovial fluid from patients with RA and osteoarthritis (OA) were measured by ELISA. Synovial fluid cells and peripheral blood cells from patients with RA were analyzed by flow cytometry. Sema4D expression of synovium were also observed by histological and immunohistochemical methods. Results Serum levels of soluble Sema4D were increased in RA in comparison to healthy individuals (11.1±8.5 ng/ml and 5.7±2.7 ng/ml, respectively; p<0.0001). Serum levels of soluble Sema4D in OA and other diseases were slightly increased but it's not significant. In synovial fluid, soluble Sema4D were detected similarly in sera of RA (11.8±7.0 ng/ml). In contrast, Sema4D was not detected in synovial fluid of OA. The levels of serum soluble Sema4D was correlated with disease activities of RA such as DAS28 (r=0.383, p<0.01), CRP (r=0.346, p<0.01), rheumatoid factor (r=0.328, p<0.01), and urinary deoxypyridinoline (r=0.318, p<0.05). The change of serum soluble Sema4D was correlated with the change of DAS28 in RA patients treated with bologics. The infiltrations of Sema4D expressing cells were observed in RA synovium. Compared to healthy individuals, the cell surface expression of sema4D was decreased in CD3+ cells and CD14+ cells in peripheral blood and synovial fluids of RA patients. The treatment with ADAMTS14, which is upregulated in RA patients reduce the expression of cell surface Same4D. In addition soluble Sema4D stimulates IL-6 and TNF-alpha production from PBMC. Conclusions Soluble Sema4D was shown to be elevated in RA and is derived from T cells and monocytes in peripheral blood and synovial fluid by shedding from cell surface. Increased soluble Sema4D may play an important role in immune activation and bone resorpotion in RA. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3513
    Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):854-855. DOI:10.1136/annrheumdis-2014-eular.3513 · 10.38 Impact Factor
  • Source
    Toshio Tanaka · Yoshihiro Hishitani · Atsushi Ogata
    [Show abstract] [Hide abstract]
    ABSTRACT: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation, systemic inflammation, and immunological abnormalities. Because cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 play a major role in the development of RA, their targeting could constitute a reasonable novel therapeutic strategy for treating RA. Indeed, worldwide clinical trials of TNF inhibiting biologic disease modifying antirheumatic drugs (bDMARDs) including infliximab, adalimumab, golimumab, certolizumab pegol, and etanercept as well as the humanized anti-human IL-6 receptor antibody, tocilizumab, have demonstrated outstanding clinical efficacy and tolerable safety profiles, resulting in worldwide approval for using these bDMARDs to treat moderate to severe active RA in patients with an inadequate response to synthetic disease modifying antirheumatic drugs (sDMARDs). Although bDMARDs have elicited to a paradigm shift in the treatment of RA due to the prominent efficacy that had not been previously achieved by sDMARDs, a substantial percentage of patients failed primary or secondary responses to bDMARD therapy. Because RA is a heterogeneous disease in which TNF-α and IL-6 play overlapping but distinct pathological roles, further studies are required to determine the best use of TNF inhibitors and tocilizumab in individual RA patients.
    Targets & therapy 04/2014; 8:141-153. DOI:10.2147/BTT.S37509
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective To evaluate the efficacious noninferiority of subcutaneous tocilizumab injection (TCZ-SC) monotherapy to intravenous TCZ infusion (TCZ-IV) monotherapy in Japanese patients with rheumatoid arthritis (RA) with an inadequate response to synthetic and/or biologic disease-modifying antirheumatic drugs (DMARDs). Methods This study had a double-blind, parallel-group, double-dummy, comparative phase III design. Patients were randomized to receive TCZ-SC 162 mg every 2 weeks or TCZ-IV 8 mg/kg every 4 weeks; no DMARDs were allowed during the study. The primary end point was to evaluate the noninferiority of TCZ-SC to TCZ-IV regarding the American College of Rheumatology criteria for 20% improvement in disease activity (ACR20) response rates at week 24 using an 18% noninferiority margin. Additional efficacy, safety, pharmacokinetic, and immunogenicity parameters were assessed. ResultsAt week 24, ACR20 response was achieved in 79.2% (95% confidence interval [95% CI] 72.9, 85.5) of the TCZ-SC group and in 88.5% (95% CI 83.4, 93.5) of the TCZ-IV group; the weighted difference was -9.4% (95% CI -17.6, -1.2), confirming the noninferiority of TCZ-SC to TCZ-IV. Remission rates of the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate and the Clinical Disease Activity Index at week 24 were 49.7% and 16.4% in the TCZ-SC group and 62.2% and 23.1% in the TCZ-IV group, respectively. Serum trough TCZ concentrations were similar between the groups over time. Incidences of all adverse events and serious adverse events were 89.0% and 7.5% in the TCZ-SC group and 90.8% and 5.8% in the TCZ-IV group, respectively. Anti-TCZ antibodies were detected in 3.5% of the TCZ-SC group; no serious hypersensitivity was reported in these patients. ConclusionTCZ-SC monotherapy demonstrated comparable efficacy and safety to TCZ-IV monotherapy. TCZ-SC could provide additional treatment options for patients with RA.
    03/2014; 66(3). DOI:10.1002/acr.22110
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background/aims: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in patients with rheumatoid arthritis (RA) but have several side effects including mucosal damage in the small intestine. We aimed to evaluate whether the small bowel injury is ameliorated by switching from nonselective NSAIDs to celecoxib in patients with RA. Methods: Sixteen patients with RA who were treated with nonselective NSAIDs were enrolled in this study. Nonselective NSAIDs were converted to celecoxib for 12 weeks. Capsule endoscopy was performed before and after treatment with celecoxib. Videos were screened by gastroenterologists blinded to the patients' treatment. Results: Before the administration of celecoxib, reddened folds, denuded areas, petechiae/red spots and mucosal breaks were observed in 63, 63, 88 and 69% of the patients, respectively. In the 14 patients who completed this study, conversion to celecoxib significantly reduced the number of petechiae/red spots, the number of mucosal breaks, and Lewis scores. RA activity and cytokine levels in the peripheral blood were not significantly different before and after treatment with celecoxib. Conclusions: The incidence of small bowel injury by nonselective NSAIDs is high in patients with RA. Conversion from nonselective NSAIDs to celecoxib can be useful for protecting patients with RA from small bowel injury.
    Digestion 02/2014; 89(2):124-132. DOI:10.1159/000357229 · 2.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin-6 (IL-6) is a cytokine with redundant and pleiotropic activities, and its synthesis is tightly regulated by transcriptional and posttranscriptional mechanisms. When infections and tissue injuries occur, IL-6 synthesis is promptly induced and provides an emergent signal that contributes to host defense through the stimulation of acute-phase responses, immune reactions, and hematopoiesis. After the environmental stress is removed from the host, the production of IL-6 is terminated. However, dysregulated continual synthesis of IL-6 is involved in the development of chronic inflammatory autoimmune diseases. For this reason, tocilizumab, a humanized anti-IL-6 receptor antibody, was developed. Worldwide clinical trials have demonstrated the outstanding efficacy of tocilizumab in rheumatoid arthritis, systemic juvenile idiopathic arthritis, and Castleman's disease; thus, a new era has come for the treatment of these diseases, which were previously considered intractable. Moreover, favorable results from off-label use of tocilizumab strongly suggest that it will be widely applicable for various refractory inflammatory autoimmune diseases. In this context, the mechanism for the continual synthesis of IL-6 needs to be elucidated in order to investigate the pathogenesis of specific diseases and to facilitate the development of more specific therapeutic strategies.
    Seminars in Immunology 02/2014; 26(1). DOI:10.1016/j.smim.2014.01.009 · 5.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Semaphorins are involved in a wide range of biological processes, including neuronal axon guidance, angiogenesis, immune modulation and osteogenesis (1, 2). Semaphorin 3A (Sema3A) suppress osteoclast function and increase osteoblast function (3). Semaphorin 4D (Sema4D), which is expressed by osteoclast, suppress osteoblast function (4). Sema4D and 3A might be key mediators of osteoimmunology in rheumatoid arthritis (RA), which have immune activation associated bone destruction. Objectives To determine the pathogenic role of Sema3A and Sema4D in RA, we evaluated the serum level of Sema3A and Sema4D in RA patients. Methods Concentrations of Sema3A and Sema4D in 102 RA patients and 26 normal controls were measured by ELISA (Mybiosource). Results The serum concentrations of Sema4D in RA patients and normal controls were 11.16±8.49 and 5.87±3.10ng/ml respectively (p<0.00001). The serum concentrations of Sema 3A in RA patients and normal controls were 8.97±3.71 and 6.65±3.75 ng/ml respectively (p<0.01). Serum concentrations of Sema4D in RA patients were associated with disease activity (DAS28 r=0.38, p<0.01, CRP r=0.34, p<0.01), rheumatoid factor (RF) (r=0.33, p<0.01) and marker of bone metabolism (urine deoxypyridinoline r=0.32 p<0.05). However serum Sema3A didn’t associated with disease activity and marker of bone metabolism. Conclusions Serum concentration of Sema3A and Sema4D were elevated in RA patients. In particular Sema4D showed association with disease activity, RF, and marker of bone metabolism. Semaphorins may play an important role in RA by immune activation, angiogenesis, increasing primary afferent sensory fibers with sympathetic nerve fiber repulsion in synovium, and bone destruction in joints. Disclosure of Interest None Declared
    Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A820-A820. DOI:10.1136/annrheumdis-2013-eular.2437 · 10.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Recent cumulative evidence suggests that early therapeutic intervention by DMARDs including MTX could prevent progression of RA. However, it is not clarified how early and which population of the patients should be taken early therapeutic intervention by DMARDs. Previously we reported that the patients with early-onset UA (EUA) showing high-titer anti-citrullinated peptide antibodies (ACPA) (>15 U/ml) developed RA within a year at high-rate (>80%) (ref.1). Objectives To examine whether very early therapeutic intervention of MTX could prevent development of RA in the patients with EUA showing high-titer of ACPA. Methods A prospective controlled study was conducted. The total number of 48 patients with UA showing high-titer of ACPA (>15 U/ml) who have never treated with any non-biologic DMARDs or biologics. All patients were fulfilled with 1994 JCR classification criteria for early RA (ref.2) but not 1987 ACR classification for RA. They participated in this study with given written informed consents and divided into two groups according to their decision. One group was treated with MTX concomitant with corticosteroid (PSL< 10mg/day) and/or NSAID (MTX+ Group, n=30). The other was treated without MTX (MTX- Group, n=18). Primary endpoint was development of RA defined by fulfilling 1987 ACR classification for RA at a time point of one year after the entry. Supplementally bone-progression was assessed by Heijdi-modified Sharp scores (H-S score). Results As shown in Figure 1(Kaplan-Meier), 5 of the 30 patients (16.7%) in the MTX+ Group developed RA compared with 14 of the 18 patients (77.8%) in the MTX- Group (HR 0.214 [95% CI 0.093-0.495], p < 0.001). Although the mean interval changes from the baseline of H-S score per year showed no significant differences in the two groups (MTX+ versus MTX- : 2.0 (SD7.6) versus 2.9 (SD4.7), p = 0.312), the number of patients without obvious radiographical progression was relatively more in MTX+ (18 /23, 78.3%) compared to in MTX- (6 /11, 54.5%). In addition, there were no particular findings regarding to adverse events. Conclusions Although short-term observation, very early therapeutic intervention of MTX might prevent development of RA in some populations of EUA. References Disclosure of Interest None Declared
    Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A244-A244. DOI:10.1136/annrheumdis-2013-eular.763 · 10.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background In treating RA patients with etanercept (ETN) or adalimumab (ADA), influence of concomitant disease-modifying antirheumatic drugs (DMARDs) (methotrexate [MTX], bucillamine, salazosulfapyridine, tacrolimus, and mizolibin) and prednisolone (PSL) on biologic inefficacy still remains controversial. Objectives The objective of this study is to compare the effect of DMARDs and PSL on biologic inefficacy of ETN and ADA, and to investigate the index of subcutaneous anti-TNF biologics selection in RA patients. Methods 284 RA patients who were followed-up more than 6 months after starting ETN (184 patients / 164 female 20 male / age 55.3y / disease duration 9.5y / pre DAS28-CRP 4.1 / 1st Bio 148 / 2nd or later Bio 36) or ADA (100 patients / 87 female 13 male / age 51.6y / disease duration 9.9y / pre DAS28-CRP 4.2 / 1st Bio 60 / 2nd or later Bio 40) were enrolled, and correlation between biologic inefficacy and clinical parameters including concomitant DMARDs and PSL were evaluated. Results Drug inefficacy was monitored in 20.7% of ETN (1st Bio 16.9% / 2nd or later Bio 36.1%) and 28.0% of ADA (1st Bio 21.7% / 2nd or later Bio 37.5%) (ETN vs. ADA; P=0.16). Mean treatment continuation duration was 32.9 months in ETN (inefficacy group 21.6 months vs. efficacy group 42.7 months) and 15.5 months in ADA (inefficacy group 9.8 months vs. efficacy group 20.8 months), and treatment continuation duration of inefficacy group was significantly longer in ETN compared to ADA (P<0.01). In ETN, inefficacy group showed higher dose of concomitant PSL (7.0 vs. 4.4 mg/day; P<0.001) and higher pre DAS28-CRP (4.5 vs. 4.1; P<0.05) compared to efficacy group. In ADA, inefficacy group showed lower dose of concomitant MTX (4.6 vs. 7.0 mg/week; P<0.01) and higher pre DAS28-CRP (4.5 vs. 3.9; P<0.01) compared to efficacy group. As for concomitant dose of MTX, when treated less than 6mg/week, inefficacy rate was significantly higher in ADA (36.5%) compared to ETN (21.0%) (P<0.05). However, those who were treated more than 8mg/week MTX, inefficacy rate was similar (ETN 19.0% vs. ADA 18.8%). In ETN, inefficacy rate was 8.2% when concomitant PSL was ≤4mg/day, while it was significantly higher (28.8%) in those who were treated more than ≥5mg/day PSL (P<0.001). PSL showed no significant correlation with inefficacy rate of ADA. Age, sexuality, body mass index, duration of disease, and dose of other DMARDs did not show any significant correlation with inefficacy rate of ETN and ADA. Conclusions When choosing ETN or ADA in the treatment of RA, concomitant MTX ≥8mg/week or PSL ≥5mg/day should be taken into consideration to avoid drug inefficacy. Disclosure of Interest None Declared
    Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A237-A237. DOI:10.1136/annrheumdis-2013-eular.742 · 10.38 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Ultrashort, e.g., picosecond or femtosecond, electron beams are useful for electro-magnetic radiation production in terahertz (THz) range due to the inverse of 1 ps bunch length corresponding to the frequency of 1 THz. The electron beams were generated by a photocathode radio-frequency (RF) gun linac. Electron beams with energy of ̃4 MeV at the RF gun exit were accelerated up to ̃30 MeV in a linac. The accelerated electron beams were compressed by a magnetic bunch compressor, resulting in femtosecond pulse width. THz radiation of the order on 0.1 THz based on coherent Cherenkov radiation (CCR) using hollow dielectric tubes and Smith-Purcell radiation (SPR) using a metallic grating or metasurface were reported.
    IEEJ Transactions on Electronics Information and Systems 01/2014; 134(4):502-509. DOI:10.1541/ieejeiss.134.502
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective. To evaluate what types of DNA damages are detected in rheumatoid arthritis (RA). Methods. The DNA adducts such as 8-oxo-hydroxy-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), 1,N(6)-etheno-2'-deoxyadenosine ( ε dA), and heptanone-etheno-2'-deoxycytidine (H ε dC) in genomic DNAs, derived from whole blood cells from 46 RA patients and 31 healthy controls, were analyzed by high-performance liquid chromatography tandem mass spectrometry, and their levels in RA patients and controls were compared. In addition, correlation between DNA adducts and clinical parameters of RA was analyzed. Results. Compared with controls, the levels of H ε dC in RA were significantly higher (P < 0.0001) and age dependent (r = 0.43, P < 0.01), while there was no significant difference in 8-oxo-dG and ε dA accumulation between RA patients and controls. H ε dC levels correlated well with the number of swollen joints (r = 0.57, P < 0.0001) and weakly with the number of tender joints (r = 0.26, P = 0.08) of RA patients, while they did not show a significant association with serological markers such as C-reactive protein and matrix metalloproteinase 3. Conclusion. These findings indicate that H ε dC may have some influence on the development of RA and/or its complications.
    10/2013; 2013(23):183487. DOI:10.1155/2013/183487

Publication Stats

2k Citations
342.11 Total Impact Points


  • 1992–2015
    • Osaka University
      • • Division of Respiratory Medicine, Allergy and Rheumatic Diseases
      • • Graduate School of Medicine
      • • Immunopathology Group
      • • Department of Internal Medicine
      Suika, Ōsaka, Japan
    • University of Tsukuba
      • Institute of Clinical Medicine
      Tsukuba, Ibaraki, Japan
  • 1990–2015
    • Osaka City University
      • • Department of Neurosurgery
      • • Department of Dermatology
      • • Third Department of Internal Medicine
      Ōsaka, Ōsaka, Japan
  • 2006–2009
    • Osaka Prefectural Medical Center for Respiratory and Allergic Diseases
      Ōsaka, Ōsaka, Japan
  • 1998–2005
    • Hyogo College of Medicine
      • Department of Internal Medicine
      Nishinomiya, Hyōgo, Japan