Publications (42)106.37 Total impact
-
Article: Expansion of range of joint motion following treatment of systemic sclerosis with tocilizumab.
[show abstract] [hide abstract]
ABSTRACT: Systemic sclerosis (SSc) presents stiffness of extremities due to sclerosis of the tissue especially at fingers, hands, and forearms. Here we report the case of a patient with diffuse cutaneous SSc who was administered anti-interleukin-6 receptor antibody tocilizumab (TCZ). Skin condition of SSc is evaluated by pinching the skin according to the Rodnan skin score, but sometimes tissue atrophy results in overestimation of the condition. To understand how the extremities softened after initiation of TCZ, we observed mobility of extremities. Range of motion (ROM) of joints was measured every four months after initiation of TCZ. The patient presented not only reduction of Rodnan score but also amelioration of mobility of extremities. The Rodnan skin score reduced from 35 to 7 within sixteen months, and ROM of most joints except ankle was expanded.Modern Rheumatology 03/2013; · 1.58 Impact Factor -
Article: A case of Behçet’s disease treated with a humanized anti-interleukin-6 receptor antibody, tocilizumab
[show abstract] [hide abstract]
ABSTRACT: A 47-year-old female patient with Behçet’s disease had been treated with colchicine, prednisolone, cyclosporine A, and infliximab. Because she relapsed, however, treatment with tocilizumab, a humanized anti-interleukin 6 receptor antibody, was started. This treatment suppressed the patient’s clinical manifestations, including ocular attacks, for 1year and improved her visual acuity. This experience indicates that tocilizumab may constitute a therapeutic option for refractory Behçet’s disease. KeywordsBehçet’s disease–IL-6–TocilizumabModern Rheumatology 04/2012; 22(2):298-302. · 1.58 Impact Factor -
Article: Pathological role of interleukin-6 in psoriatic arthritis.
[show abstract] [hide abstract]
ABSTRACT: Psoriatic arthritis (PsA) is a clinical manifestation of psoriatic disease. Although the pathogenesis of PsA remains unknown, PsA can be managed by treatments similar to those used for rheumatoid arthritis (RA). Because interleukin-(IL-) 6 has been suggested to have a pathogenic role in PsA, a humanized anti-IL-6 receptor antibody tocilizumab treatment for PsA was recently tried. However, the efficacy of tocilizumab for PsA was not favorable. This suggests that the pathogenic roles of IL-6 in PsA and RA are different. In RA, tumor necrosis factor (TNF) primarily contributes to the arthritis effector phase and IL-6 contributes to the arthritis priming phase. In PsA, the TNF-related effector phase is similar to that in RA, but the IL-6-related priming phase might not be critical. This paper discusses the role of IL-6 in PsA.Arthritis. 01/2012; 2012:713618. -
Article: Tocilizumab for the treatment of rheumatoid arthritis and other systemic autoimmune diseases: current perspectives and future directions.
[show abstract] [hide abstract]
ABSTRACT: Interleukin (IL)-6 is a cytokine featuring redundancy and pleiotropic activity. While IL-6, when transiently produced, contributes to host defense against acute environmental stress, continuous dysregulated IL-6 production plays a significant pathological role in several systemic autoimmune diseases. In response to the expectation that IL-6 blockade would constitute a novel therapeutic strategy for the treatment of these diseases, tocilizumab, a humanized anti-IL-6 receptor antibody, was developed. Clinical trials have verified the efficacy and the safety of tocilizumab for patients with rheumatoid arthritis, resulting in approval of this innovative biologic for the treatment of rheumatoid arthritis in more than 90 countries worldwide. Pathological analyses of the effect of IL-6 on the development of autoimmune diseases and a considerable number of case reports and pilot studies have also indicated the beneficial effects of this antibody on other systemic autoimmune diseases, including systemic lupus erythematosus, systemic sclerosis, polymyositis, and large-vessel vasculitis.International Journal of Rheumatology 01/2012; 2012:946048. -
Article: Safety and efficacy of tocilizumab for the treatment of rheumatoid arthritis.
[show abstract] [hide abstract]
ABSTRACT: Because of the pathological role of IL-6 in rheumatoid arthritis (RA), tocilizumab (TCZ), a humanized anti-IL-6 receptor monoclonal antibody, was expected to improve inflammation and joint destruction of RA. Indeed, randomized clinical trials demonstrated the clinical efficacy of TCZ as monotherapy or combined with methotrexate (MTX) for RA patients with inadequate responses to disease-modifying antirheumatic drugs, MTX or tumor necrosis factor (TNF) inhibitors. Although long-term tolerability for TCZ is superior to that for TNF inhibitors, information regarding the potency of drug free remission of TCZ is limited at present. In terms of its safety profile, the general risk of infection when using TCZ is comparable to that of TNF inhibitors. TCZ has some advantage in RA patients who can not use MTX and are non-responders to TNF inhibitors. In conclusion, TCZ is one of the most prospective next generation biologics for the treatment of RA.Clinical medicine insights. Arthritis and musculoskeletal disorders. 01/2012; 5:27-42. -
Chapter: Tocilizumab for the Treatment of AA Amyloidosis
11/2011; , ISBN: 978-953-307-795-6 -
Article: Psoriatic arthritis in two patients with an inadequate response to treatment with tocilizumab.
[show abstract] [hide abstract]
ABSTRACT: Psoriatic arthritis (PsA) is considered as one of the seronegative spondylarthropathies. Like rheumatoid arthritis (RA), the increased production of interleukin (IL)-6 suggests a pathogenic role of IL-6 in PsA. However, whether humanized anti-IL-6 receptor antibody such as tocilizumab (TCZ) might be effective for PsA as well as RA has yet to be determined. We report herein two cases of PsA treated using TCZ. Although, TCZ treatment resulted in disappearance of serum CRP in both patients, arthritis and skin lesions were not improved despite 6-month administration of TCZ. In contrast, tumor necrosis factor (TNF) inhibitor proved effective against arthritis and skin lesions in these patients. Collectively, these findings not only indicate that IL-6 has distinct pathological roles in RA and PsA, but also suggest that TNF inhibitor therapy (but not TCZ) is effective for arthritis and skin lesions of PsA.Joint, bone, spine: revue du rhumatisme 09/2011; 79(1):85-7. · 2.25 Impact Factor -
Article: A case of Behçet's disease treated with a humanized anti-interleukin-6 receptor antibody, tocilizumab.
[show abstract] [hide abstract]
ABSTRACT: A 47-year-old female patient with Behçet's disease had been treated with colchicine, prednisolone, cyclosporine A, and infliximab. Because she relapsed, however, treatment with tocilizumab, a humanized anti-interleukin 6 receptor antibody, was started. This treatment suppressed the patient's clinical manifestations, including ocular attacks, for 1 year and improved her visual acuity. This experience indicates that tocilizumab may constitute a therapeutic option for refractory Behçet's disease.Modern Rheumatology 07/2011; 22(2):298-302. · 1.58 Impact Factor -
Article: Therapeutic effect of tocilizumab on two patients with polymyositis.
Rheumatology (Oxford, England) 07/2011; 50(7):1344-6. · 4.24 Impact Factor -
Article: Tocilizumab, a humanized anti-interleukin-6 receptor antibody, ameliorated clinical symptoms and MRI findings of a patient with ankylosing spondylitis.
[show abstract] [hide abstract]
ABSTRACT: Ankylosing spondylitis (AS) is a chronic inflammatory osteoarticular disease. Although the etiology remains unknown, proinflammatory cytokines, such as tumor necrosis factor α and interleukin-6, have been implicated in the development of AS. Here, we report that a patient with AS, whose disease had been refractory to conventional treatment regimens and who needed to receive continuous corticosteroid, responded well to tocilizumab. While further clinical evaluation is required, tocilizumab may be an optional treatment for AS.Modern Rheumatology 02/2011; 21(4):436-9. · 1.58 Impact Factor -
Article: Successful treatment of acquired hemophilia A, complicated by chronic GVHD, with tocilizumab.
[show abstract] [hide abstract]
ABSTRACT: A 65-year-old woman who had suffered from chronic graft-versus-host disease (GVHD) presented with extensive purpura and was diagnosed with acquired hemophilia A. Because she was refractory to corticosteroids and her condition was complicated with diabetes mellitus, glaucoma, and hypoglobulinemia, she was treated with tocilizumab. Tocilizumab treatment increased the activity of factor VIII in a rapid and sustained manner, leading to a reduction of the prednisolone dose. Tocilizumab may thus be an optional treatment modality for acquired hemophilia A.Modern Rheumatology 01/2011; 21(4):420-2. · 1.58 Impact Factor -
Article: The skin of patients with systemic sclerosis softened during the treatment with anti-IL-6 receptor antibody tocilizumab.
[show abstract] [hide abstract]
ABSTRACT: SSc is an autoimmune disease characterized by fibrosis of the skin and internal organs. Although the aetiology remains uncertain, many reports have suggested that IL-6 is involved in SSc pathogenesis. Tocilizumab, an anti-IL-6 receptor antibody, is an anti-arthritis medicine that works through the blockade of IL-6 functions. To examine the effect of tocilizumab on SSc, we administered tocilizumab to two SSc patients. Two dcSSc patients were administered tocilizumab at 8 mg/kg once a month for 6 months. One patient had pulmonary fibrosis assessed by CT and spirometry, and the other had chronic renal failure caused by scleroderma renal crisis. Their skin condition was monitored with a Vesmeter and the modified Rodnan total skin score (mRTSS). Skin biopsies were obtained before and after the tocilizumab treatment to investigate the histological changes. After tocilizumab treatment, both patients showed softening of the skin with reductions of 50.7 and 55.7% in the total z-score of Vesmeter hardness and 51.9 and 23.0% in the mRTSS, respectively. Histological examination showed thinning of the collagen fibre bundles in the dermis. The creatinine clearance in the patient with chronic renal failure improved from 38 to 55 ml/min. However, the fibrotic changes in the lung in the other patient remained unchanged. In the two cases of SSc that we report here, softening of the skin was observed during the treatment with tocilizumab.Rheumatology (Oxford, England) 12/2010; 49(12):2408-12. · 4.24 Impact Factor -
Article: Tocilizumab for the treatment of rheumatoid arthritis.
[show abstract] [hide abstract]
ABSTRACT: Tocilizumab is a humanized anti-IL-6 receptor monoclonal antibody, which binds to circulating soluble IL-6 receptor and membrane-expressed IL-6 receptor, inhibiting IL-6 binding to both forms of IL-6 receptor. Several Phase III clinical trials demonstrate the clinical efficacy of tocilizumab as monotherapy or with disease-modifying anti-rheumatic drugs for adult patients with moderately to severely active rheumatoid arthritis. Tocilizumab in combination with methotrexate after 24 weeks of treatment could induce disease remission in 30% of patients with rheumatoid arthritis refractory to anti-TNF antagonist therapy. The most common adverse reactions reported in clinical studies are upper respiratory tract infection, nasopharyngitis, headache, hypertension and mild, reversible increases in alanine aminotransferase enzymes. Serious adverse reactions include infections, gastrointestinal perforations and hypersensitivity reactions, including anaphylaxis. The clinical efficacy and safety of tocilizumab has led to the approval of this innovative drug for the treatment of rheumatoid arthritis in more than 70 countries worldwide.Expert Review of Clinical Immunology 11/2010; 6(6):843-54. · 2.07 Impact Factor -
Article: Improvement of HbA1c during treatment with humanised anti-interleukin 6 receptor antibody, tocilizumab.
Annals of the rheumatic diseases 10/2010; 70(6):1164-5. · 8.11 Impact Factor -
Article: Treatment of a patient with remitting seronegative, symmetrical synovitis with pitting oedema with a humanized anti-interleukin-6 receptor antibody, tocilizumab.
Rheumatology (Oxford, England) 12/2009; 49(4):824-6. · 4.24 Impact Factor -
Article: Successful treatment of reactive arthritis with a humanized anti-interleukin-6 receptor antibody, tocilizumab.
Arthritis & Rheumatism 11/2009; 61(12):1762-4. · 7.87 Impact Factor -
Article: Minimal influence of tocilizumab on IFN-gamma synthesis by tuberculosis antigens.
[show abstract] [hide abstract]
ABSTRACT: Interferon gamma (IFN-gamma) production is a critical step of antituberculosis (anti-TB) immune response. The purpose of this study was to determine the influences of biologics, including the interleukin (IL)-6 receptor-inhibitor tocilizumab (TCZ), and tumor necrosis factor (TNF) antagonists infliximab (INF) and etanercept (ETA), on Mycobacterium tuberculosis (MTB) antigen-induced IFN-gamma production. MTB antigen (ESAT-6 and CFP-10)-induced IFN-gamma-releasing assay was performed with or without addition of biologics (TCZ, ETA, and INF) using whole blood from patients with active TB. ETA and INF inhibited IFN-gamma production in a dose-dependent manner. In whole blood from TB patients, ESAT-6 stimulated significant production of IFN-gamma (1.30 +/- 1.95 IU/ml), and TCZ did not inhibit IFN-gamma production (1.56 +/- 1.88 IU/ml). IFN-gamma production by ESAT-6 was inhibited by ETA and INF (0.98 +/- 1.74, 0.75 +/- 1.66 IU/ml, respectively). CFP-10 stimulated significant production of IFN-gamma (1.46 +/- 1.60 IU/ml), and TCZ did not inhibit IFN-gamma production (1.51 +/- 1.77 IU/ml). IFN-gamma production by CFP-10 was inhibited by ETA and INF (0.91 +/- 0.99, 0.72 +/- 0.88 IU/ml, respectively). TCD did not inhibit MTB antigen-induced IFN-gamma production. As IFN-gamma production is important in antimycobacterial host defenses, the minimal influence of TCZ on IFN-gamma-releasing assay suggests a low risk of latent TB infection reactivation during tocilizumab therapy.Modern Rheumatology 11/2009; 20(2):130-3. · 1.58 Impact Factor -
Article: iTRAQ-based proteomic identification of leucine-rich alpha-2 glycoprotein as a novel inflammatory biomarker in autoimmune diseases.
[show abstract] [hide abstract]
ABSTRACT: To identify a novel serum biomarker of disease activity in inflammatory autoimmune disorders. Sera obtained from rheumatoid arthritis (RA) patients before and after anti-TNF therapy were analysed by iTRAQ (isobaric tags for relative and absolute quantitation) quantitative proteomic analysis and further validated by ELISA. Of 326 proteins identified by proteomic analysis, increased serum levels of leucine-rich alpha-2 glycoprotein (LRG) was identified in RA patients before therapy. Serum LRG concentrations were significantly elevated in RA patients compared with healthy controls and decreased after anti-TNF therapy. Furthermore, serum LRG concentrations correlated with disease activity in RA and Crohn's disease (CD). Interestingly, in a subpopulation of patients with active CD and normal C-reactive protein levels, serum LRG concentrations were elevated. LRG represents a novel serum biomarker for monitoring disease activity during therapy in autoimmune patients, particularly useful in patients with active disease but normal CRP levels.Annals of the rheumatic diseases 10/2009; 69(4):770-4. · 8.11 Impact Factor -
Article: Imatinib mesylate inhibited rat adjuvant arthritis and PDGF-dependent growth of synovial fibroblast via interference with the Akt signaling pathway.
[show abstract] [hide abstract]
ABSTRACT: Overgrowth of the synovium plays an important role in the pathogenesis of rheumatoid arthritis (RA). Platelet-derived growth factor (PDGF) is one of the most potent mitogenic factors of synovial cells, and imatinib mesylate (imatinib) is a specific inhibitor of the PDGF receptor tyrosine kinase. The aim of this study was to elucidate the anti-rheumatic activity of imatinib. The in vivo effects of imatinib were assessed by evaluating the sequential manifestation of adjuvant-induced arthritis in rats using paw volume and clinical scores. Imatinib was found to inhibit rat adjuvant-induced arthritis, but the inhibitory effects were incomplete. To confirm the mechanism of anti-rheumatic-activity of imatinib, we assessed the in vitro effects of imatinib on the proliferation of RA synovial fibroblast-like cells (RASFs) using a MTT assay. Intracellular signaling of PDGF was evaluated by Western blot analysis. Platelet-derived growth factor was found to induce a significant proliferation of RASFs, while imatinib inhibited PDGF-induced proliferation of RASF. Imatinib also inhibited PDGF-induced phosphorylation of the PDGF receptor and Akt, whereas constitutive activated extracellular signal-regulated kinase was not inhibited by imatinib. In contrast, imatinib did not inhibit transforming growth factor beta- and basic fibroblast growth factor-induced proliferation of RASF. Oral administration of imatinib ameliorated adjuvant-induced arthritis in rats, and it inhibited PDGF-induced RASF proliferation through disruption of the PDGF-R to Akt kinase signaling pathway. Because imatinib cannot inhibit the non-PDGF-dependent proliferation of RASFs, the anti-rheumatic effect of imatinib may be incomplete. The development of inhibitors of RASF proliferation may lead to the successful treatment of RA.Modern Rheumatology 08/2009; 19(5):522-9. · 1.58 Impact Factor -
Article: Preventative effect of a flavonoid, enzymatically modified isoquercitrin on ocular symptoms of Japanese cedar pollinosis.
[show abstract] [hide abstract]
ABSTRACT: Flavonoids are nutrients that exert anti-allergic effects. We investigated the preventative effect of enzymatically modified isoquercitrin (EMIQ), a flavonoid, to relieve the symptoms of Japanese cedar pollinosis. In a parallel-group, double-blind placebo-controlled study design, 24 subjects with Japanese cedar pollinosis took 100mg EMIQ or a placebo for 8 weeks, starting 4 weeks prior to the onset of pollen release. Subjective symptoms, ADL scores and the usage of drugs were recorded daily, and the QOL score was obtained every 4 weeks. Blood sampling was performed before and after the study to measure serum levels of IgE and flavonoids. During the entire study period, ocular symptom + medication score for the EMIQ group was significantly lower (p < 0.05) than that of the placebo group. When limited to the period, ocular symptom scores (p < 0.05, weeks 5-6), and ocular congestion scores (p < 0.05, weeks 5-6) for the EMIQ group was significantly lower than that for the placebo group while other scores for the EMIQ group, such as ocular itching scores (p = 0.09, weeks 4-5), lacrimation scores (p = 0.07, weeks 5-6), and ocular congestion scores (p = 0.06, weeks 4-5), all tended to be lower. However no significant differences were found in nasal symptoms between the two groups. Serum concentrations of IgE were not significantly downregulated but the serum concentrations of quercetin and its derivatives were elevated significantly by the intake of EMIQ. CONCLUSIONs: Intake of the quercetin glycoside EMIQ proved to be effective for the relief of ocular symptoms caused by Japanese cedar pollinosis.Allergology International 06/2009; 58(3):373-82.
Top co-authors
Top Journals
Institutions
-
2003–2012
-
Osaka City University
Ōsaka-shi, Osaka-fu, Japan
-
-
2009
-
Osaka University
Ibaraki, Osaka-fu, Japan
-
-
1999–2005
-
Hyogo College of Medicine
- Department of Internal Medicine 4
Nishinomiya, Hyogo-ken, Japan
-
