Volume 21 • Supplement 2011

ABSTRACT SUPPLEMENT

The 55th Annual Scientific Meetingand

The 20th International Rheumatology Symposium

July 17-20, 2011Kobe

JAPAN COLLEGE OFRHEUMATOLOGY

ABSTRACT SUPPLEMENT

CONTENTS

ABSTRACTS

President's Address ………………………………………… S2

Symposium …………………………………………………… S2

Current Symposium ………………………………………… S9

Next Decade Symposium …………………………………… S28

International Symposium …………………………………… S32

Educational Lecture ………………………………………… S34

Rising & Achievement Seminar ……………………………… S39

Workshop …………………………………………………… S43

International Workshop …………………………………… S167

New Generation Workshop ……………………………… S175

Basic Science ……………………………………………… S180

Case Report ……………………………………………… S188

Poster ……………………………………………………… S193

Sponsored Symposium …………………………………… S294

Luncheon Seminar ………………………………………… S297

Evening Seminar ………………………………………… S308

Hands-on Seminar ………………………………………… S313

Annual Course Lecture …………………………………… S315

AUTHORS' INDEX ……………………………………… S319

President's AddressNew development of total joint arthroplasty for Rheumatoid Ar-thritisToru SuguroDepartment of Orthopaedic Surgery, Toho University School ofMedicine

For rheumatoid arthritis is necessary to have reconstructive sur-gery, because inflammatory changes will make the joint cartilagedamages. The incidence of joints involvements should be so high onthe hand, finger, elbow, hip, knee, ankle and foot. The joint destruc-tion and deformity would be occurred with the duration of inflam-matory process. The best reconstruction methods for RA destroyedjoints are joints replacement, in Asia most total joint prosthesis areimported from United States and European countries. The importedimplant does not suitable for Asian patients, for this reason we star-ted to develop new total prostheses for Asia since 1980. First totalknee prostheses was developed 1985,and then we have been gettinggood clinical results. Next generation FINE total knee prosthesiswas developed 2000, and this implant has been showing so goodROM and clinical results for RA patients. On RA patients, it is nec-essary to make other joint prosthesis. We developed the elbow joint,ankle joint, finger joint for RA patient. However the implant has alot of complications while longtime using, the one of the reason iswear and oxidization of poliechyren. Now in Japan, it is abatable touse the Blend-E polyethylene for keeping the longevity. Still wehave to make a big revolutions and development for RA patients tokeep a good quality functions in daily living.

SymposiumS1-1Novel therapies for vasculitis syndromeShoichi OzakiDivision of Rheumatology and Allergology, Department of InternalMedicine, St. Marianna University School of Medicine, Kawasaki,Japan

A therapeutic strategy for vasculitis syndrome has been estab-lished, and global evidence has been accumulated by severalrandomized controlled trials (RCTs), especially in Takayasu’s arteri-tis, giant cell arteritis and anti-neutrophil cytoplasmic antibody (AN-CA)-associated vasculitis (AAV). The standard regimen for Takayasu’s arteritis is glucocorticoid(GC) therapy. In GC-resistant patients, an immunosuppressive agentis added, such as cyclophosphamide (CY), methotrexate (MTX),azathioprine (AZ), and mycophenolate mofetil (MMF). Recently,anti-TNF-alpha therapy or peripheral blood stem-cell transplantationhas been employed. In giant cell arteritis, GC is also the first-line drug. Prednisoloneof 1mg/kg/day is administered to patients with ocular involvement,central nervous-system involvement or cranial nerve sign. For thoselacking these signs, prednisolone of 30 - 40 mg/day is used. Theusefulness of intravenous methylprednisolone is controversial. Sev-eral immunosuppressive agents have been used as adjunctive thera-py. Among them, MTX was proved to be good for relapse-prevent-ing and GC-sparing effects by a meta-analysis of three RCTs. Incontrast, infliximab seemed to have little adjunctive effect to GCmonotherapy. Standard therapies for AAV are high-dose GC + CY in remissioninduction and low-dose GC + AZ in remission maintenance. In EU-LAR recommendations 2009, novel therapies for refractory AAVincluded intravenous immunoglobulin (IVIG), infliximab, rituxi-mab, 15-deoxyspergualin, anti-thymocyte antibody, and MMF. Re-cently, two RCTs were reported, where rituximab was as effectiveand safe as CY in remission induction of AAV. A pilot study forJapanese patients with refractory AAV indicated the effectiveness ofrituximab in induction of re-remission. Although most of the agentsmentioned above are not approved in Japan, IVIG was approved forneurological impairment in Churg-Strauss syndrome in January,2010.

S1-2New therapy for ankylosing spondylitisKurisu TadaRheumatology and Internal Medicine, Juntendo University Schoolof Medicine

TNF inhibitor is used in various inflammatory diseases includ-ing rheumatoid arthritis, Bechet disease, Psoriasis, and inflammatorybowel disease, and has been shown to be effective. In particular,rheumatoid arthritis, TNF inhibitor resulting in a paradigm shift intreating rheumatoid arthritis, “tight control”, “treat to target” hasbeen proposed that a new treatment strategy. Finally, in 2010 TNFinhibitor was indicated for ankylosing spondylitis. In conventionaltreatment, NSAIDs are recommended as first line drug, Sulfasala-zine may be considered in patients with peripheral arthritis. Cortico-steroid injections directed to the local site of muscloskeltal inflam-mation may be considered. However, NSAIDs were the only effec-tive treatment in axial disease. In Europe and U.S, TNF inhibitor hasbeen proved an immediate effect for ankylosing spondylitis, and hasbeen shown highly effective in clinical trials in Japan. The predic-tors of a good response to TNF inhibitor were short disease duration,

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elevated C-reactive protein and younger age. While the high clinicalefficacy, however, inhibition of radiographic progression in anky-losing spondylitis is currently negative. The ankylosis of the spinehas two steps, in the first step inflammation causes erosive structuraldamage with bony defect, which are filled with fibrous repair tissue,in the second step the repair tissue becomes ossified, which is madeeasier when inflammation disappears. Therefor early diagnosis andearly use of TNF inhibitor may lead to better clinical course. Thistime, I will introduce the new treatment for ankylosing spondylitis,including the latest findings.

S1-3Systemic lupus erythematosusYoshiya TanakaThe First Department of Internal Medicine, School of Medicine,University of Occupational & Environmental Health, Japan

Systemic lupus erythematosus (SLE) is a representative autoim-mune disease and immune complexes consisting of antigens and au-toantibodies secreted from activated B cells cause severe inflamma-tion in various organs. Since often patients with SLE are refractoryto conventional treatments such as immunosuppressants and cortico-steroids, innovative approaches need to be developed. Recently, thepotential efficacy of biologics targeting B cells and cytokines hasbeen emerging in the treatment of SLE. B cell depletion therapywith anti-CD20 antibody rituximab has shown a rapid onset of effectand prolonged efficacy in refractory SLE. We also reported that rit-uximab is safe for the treatment of active SLE by a multi-centerphase I/II clinical trial. However, the placebo-controlled trials suchas EXPLORER with rituximab in SLE did not achieve satisfied re-sults and serious opportunistic infections have been reported in pa-tients with SLE treated with rituximab. In addition, other B-cell tar-geted therapies such as CD20-directed small modular immunophar-maceutical (SMIP) product (SBI-087) and anti-CD22 antibody epra-tuzumab, agents that interrupt cellular interaction among B cells, Tcells, monocyte and dendritic cells, including anti-BAFF antibodybelimumab, CTLA4-Ig fusion protein abatacept, TACI-Ig fusionprotein atacicept, and anti-IFN-alfa antbody sifalimumab also havepotential of the therapeutic application.

S1-4Novel approach to osteoporosis treatmentSakae TanakaDepartment of Orthopaedic Surgery, Faculty of Medicine, The Uni-versity of Tokyo, Tokyo, Japan

Japan is one of the most rapidly aging countries in the world.People aged 65 and over numbered 27,440,000 in 2007, which is22% of the population, and thus Japan is already in a “super-aged”society. For aged people, to maintain mobility is critical for keepingindependence, and osteoporotic fractures such as vertebral fracturesand hip fractures are the most popular cause of loss of mobility. Os-teoporosis is a burden not only for the patients but also for the soci-ety although the exact pathology has not been clarified yet. Remark-able progress has been made during the last decade in the treatmentof osteoporosis by anti-resorptive agents such as bisphosphonatesand a selective estrogen receptor modulator (SERM). However, thefracture prevention using these agents is not sufficient and severaladverse events have been recognized. In this symposium, I wouldlike to introduce novel anti-osteoporotic drugs: a novel bisphospho-nate minodronate, an anabolic agent teriparatide, and a novel SERM

basedoxifene. In addition, I will also introduce some drugs whichare under development.

S1-5Sjogren's syndromeTakayuki Sumida, Hiroto Tsuboi, Mana Iizuka, Naomi Matsuo, IsaoMatsumotoDepartment of Internal Medicine, University of Tsukuba

Sjogren’s syndrome (SS) is an autoimmune disease character-ized pathologically by lymphocytic infiltration into the lacrimal andsalivary glands, and clinically by dry eyes and mouth. Lymphocyticinfiltration is also found in the kidneys, lungs, thyroid, and liver. Im-munohistochemical studies have shown that most infiltrating lym-phocytes around the labial salivary and lacrimal glands and the kid-neys are CD4-positive αβT cells. Candidate autoantigens recognizedby T cells that infiltrate the labial salivary glands of SS have beenanalyzed and Ro/SS-A 52 kD, α-amylase, heat shock protein, TCRBV6 have been identified, Recently, we observed evidence thatmuscarinic-3 acetylcholine receptor (M3R) works as an autoantigenrecognized by T cells in patients with SS. Additionally, various au-toantibodies (autoAbs) have been identified in sera of patients withSS, and some of these autoAbs, such as anti-SS-A antibody (Ab)and anti-SS-B Ab are used as diagnostic markers. Muscarinic-3 ace-tylcholine receptor (M3R) is involved in activation of salivary andlacrimal glands. We reported that antibodies against M3R has beendetected in serum from subgroup of patients with Sjogren’s syn-drome (SS). Recently, we succeeded to establish autoimmune sia-loadenitis such as SS by cell transfer experiments using M3R-/-mice immunized with M3R peptides and Rag1-/- mice. These find-ings support the notion that the immune reaction against M3R mole-cule might play a crucial role in the generation of SS. In the presentsymposium, I will summarize the molecular mechanism of SS,present our new data on the role of M3R reactive T cells and anti-M3R Abs in the generation of SS, and discuss an antigen-specifictherapeutic strategies on SS in near future. Moreover, I will showyou the progress on the new therapies on SS using biologics such asantibodies against CD20, CD22, and BAFF.

S1-6Behcet's diseaseShunsei Hirohata1, Hirotoshi Kikuchi21Department of Rheumatology and Infectious Diseases, KitasatoUniversity School of Medicine, 2Department of Microbiology, Tei-kyo University School of Medicine

One of the most serious manifestations in Behcet’s disease issight-threatening uveitis. Although cyclosporin has been used toprevent an attack of uveitis, approximately 50% of the patients stillpresent recurrent uveitis attacks. Recently, infliximab has beenshown to be effective in suppressing the occurrence of uveitis at-tacks, and to have favorable implications for the visual prognosis ofpatients with recalcitrant Behçet's uveitis. Another intractable com-plications of Behcet’s disease include vascular involvement (vascu-lo-Behcet), neurological involvement (neuro-Behcet [NB]), and in-testinal involvement (intestinal-Behcet). The use of infliximab forvasculo-Behcet is still controversial, since some reports suggest thethrombogenicity of infliximab. NB can be classified into acute typeand chronic progressive type. Acute type NB responds to corticoste-roid therapy, and is usually self-limiting, although recurrence of theattacks sometimes takes place.　Some case reports suggest the effi-cacy of infliximab in preventing the recurrence of attacks, althoughcontrolled trials are required for confirmation. Chronic progressive

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type NB is characterized by intractable, slowly progressive neurobe-havioral changes, ataxia and dysarthria, with persistent marked ele-vation of cerebrospinal fluid (CSF) IL-6. Although chronic progres-sive NB is resistant to conventional treatment with corticosteroid,cyclophosphamide, or azathioprine, low-dose weekly methotrexate(MTX) has been shown to be effective. Recent studies with an opentrial have disclosed that infliximab inhibits the progression of neuro-logical manifestations by decreasing CSF IL-6 in patients with re-calcitrant chronic progressive NB. As to intestinal Behcet’s disease,there are several case reports, suggesting the efficacy of infliximab.However, further studies are necessary to confirm its efficacy with alarger numbers of patients.

S2-1Inhibition of cyclin-dependent kinase 4/6 for treatment of rheu-matoid arthritisHitoshi Kohsaka, Tadashi Hosoya, Hideyuki Iwai, NobuyukiMiyasakaDepartment of Medicine and Rheumatology, Tokyo, Japan

Recent research studies on rheumatoid arthritis (RA) have led todevelopment of biological agents that target specific molecules.However, we still have patients refractory to these expensive agentsand/or suffering from severe adverse events, especially infections.During our search for non-immunosupressive approaches, we foundthat intraarticular gene transfer of cyclin-dependent kinase (CDK)inhibitor to suppress CDK4/6 and thus to inhibit synovial cellgrowth was effective in treating animal models of RA. When small-molecule (sm) CDK4/6 inhibitors were tested, they suppressed pro-liferation of synovial fibroblasts (SF) in vitro and also the animalmodels without affecting lymphocyte functions. In vitro, smCDK al-so inhibited expression of stromelysin-1 (MMP-3) from SF. We as-sume that CDK4/6 inhibition has dual anti-rheumatic effects: inhibi-tion of proliferation and MMP-3 expression of SF. ChemicalCDK4/6 inhibiting compounds that are superior in the dual effectsare now being screened.

S2-2Inflammation, joint destruction and c-Fos/AP-1 in rheumatoidarthritis.Shunichi Shiozawa1, Akira Hashiramoto1, Yukihiko Aikawa21Division of Rheumatology, Kobe University Graduate School ofHealth Sciences and Medicine/ The Center for Rheumatic Diseases,Kobe University Hospital, 2Research Laboratories, Toyama Chemi-cal Co., Ltd.

Synovial mesenchymal cells, matrix metalloproteinases(MMPs), and osteoclasts are the 3 major players responsible for thepathogenesis of rheumatoid joint destruction. First, synovial mesenchymal cells, internally driven by a transcrip-tion factor c-Fos/AP-1, not only directly invade cartilage and boneas a granulation tissue calld ‘pannus’ but also release inflammatorycytokine interleukin-1b (IL-1b). IL-1b induces MMPs and activatesosteoclasts. Synovial cells can also present antigen to T cells todrive antigen-specific immune responses. Second, cartilaginous joint matrix can only be degraded after thefirst attack of collagen fibrils by MMPs, and importantly, most ofthe MMPs are under the control of c-Fos/AP-1 and IL-1b as well. Therefore, IL-1b and c-Fos/AP-1 influence each other’s gene ex-pression and activity, resulting in an orchestrated cross-talk that iscrucial to arthritic joint destruction, and thus, blockade of IL-1b and/or c-Fos/AP-1 can be most promising as a therapeutic target, and in

fact, a selective inhibition of c-Fos/AP-1 does resolve arthritic jointdestruction.

S2-3S1P receptor as a new target for the therapy of autoimmune dis-easesKenji ChibaPharmacology Research Laboratories I, Research Division, Mitsu-bishi Tanabe Pharma Corporation

Sphingosine 1-phosphate (S1P), a lysophospholipid mediator, isgenerated from sphingosine by sphingosine kinases and binds 5types of G protein-coupled S1P receptors. It has been well docu-mented that S1P receptor type 1 (S1P1) plays an essential role inlymphocyte egress from secondary lymphoid organs (SLO), becauselymphocytes are unable to exit from SLO to periphery in mice lack-ing lymphocytic S1P1 conditionally. FTY720 (fingolimod) is an or-ally active first-in-class S1P receptor modulator and is highly effec-tive in various experimental autoimmune disease models includingencephalomyelitis, adjuvant- or collagen-induced arthritis, and lupusnephritis. FTY720 is a structural analogue of sphingosine and is ef-fectively converted to an active metabolite, FTY720 phosphate(FTY720-P) by sphingosine kinases. FTY720-P binds to four typesof S1P receptors (S1P1, S1P3, S1P4, and S1P5) except for S1P2 andacts as an agonist at these receptors. Particularly, FTY720-P strong-ly internalizes S1P1 from the cell surface, almost completely inhib-its S1P responsiveness of lymphocytes in SLO, and acts as a func-tional antagonist at lymphocytic S1P1. Consequently, FTY720 in-hibits S1P1-dependent lymphocyte egress from SLO to decrease cir-culation of lymphocytes including autoreactive Th 17 cells and Th1cells, and shows immunomodulating effects on autoimmune diseasemodels. Recently, it has been reported that FTY720 has a superiorefficacy in relapsing remitting multiple sclerosis patients comparedto interferon-β (Phase 3, TRANSFORMS study). From these results,it is presumed that S1P1 is a novel target for the therapy of autoim-mune diseases including multiple sclerosis.

S2-4Innovation of therapy for autoimmune diseases by targetingCD26Kei OhnumaDivison of Rheumatology and Allergy, Research Hospital, Instituteof Medical Science, University of Tokyo, Tokyo, Japan

CD26 is a 110-kDa cell surface glycoprotein with known dipep-tidyl peptidase IV activity in its extracellular domain. CD26 playsan important role in infection, autoimmunity, diabetes and cancer.CD26 role in immune regulation has been extensively characterized,with our recent findings elucidating its linkage with signaling path-ways and structures involved in T cells activation as well as antigenpresenting cell -T-cell interaction. CD26 is preferentially expressedon human CD4+ memory T cells and CD4+CD45RO+CD26+ Tcells exhibit a response maximally to the recall antigen, such as teta-nus toxoid. Human Th1 cells display a higher expression of CD26and are much more sensitive to CD26-mediated costimulation thanhuman Th2 cells. While CD8+ T cells express CD26 as well asCD4+ T cells, precise role of CD26 in CD8+ T cells has not yetbeen studied. We recently investigated the effector function ofCD26-mediated costimulation of CD8+ T cells. In comparison withCD28-medaited costimulation, which is one of extensively charac-terized T cell costimulatory pathway, CD26-mediated costimulationin CD8+ T cells showed delayed proliferation than that of CD28stimulation. Moreover, the expression of Granzyme B, one of the

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major effector molecules in the cytotoxic activity of CD8+ T cells,was markedly enhanced by CD26-mediated costimulation. Further-more, with CD26-mediated costimulation, CD8+ T cells were ob-served to kill target cells in a Granzyme B-dependent manner. Next,we examined CD26-dependent organ injury by human T cells usingxenogeneic chronic GVHD (x-cGVHD) mice model. Administrationof anti-human CD26 mAb decreased onset of x-cGVHD, while hu-man lymphocytes were grafted successfully. Taken together, our da-ta strongly suggest that CD26 plays an important role in CD8+ Tcell dependent defense against immune reaction. The present studyoffers a novel notion that CD26 may become one of therapeutic tar-gets of intractable immune diseases.

S2-5Cathepsin K inhibitor for the treatment of osteoporosis andrheumatoid arthritisHiroshi TakayanagiDepartment of Cell Signaling Tokyo Medical and Dental Universi-ty / JST, ERATO

Osteoclasts attracted much attention as the crucial target in thetreatment of osteoporosis and rheumatoid arthritis. Since cathepsinK was identified and specifically detected in osteoclasts, cathepsinK inhibitor has been thought to be a specific inhibitor of osteoclasticbone resorption. We have developed a new oral inhibitor of cathe-psin K NC-2300, which efficiently suppressed in vitro osteoclast ac-tivity and in vivo bone loss in osteoporosis models. Unexpectedly,in the treatment of rat adjuvant arthritis, NC-2300 inhibited inflam-matory responses in addition to osteoclastic bone resorption. We re-vealed dendritic cells express cathepsin K, which plays an essentialrole in the TLR9 signaling required for the induction of cytokinessuch as IL-6, -12 and -23. Cathepsin K inhibitor also suppressed thedisease activity and induction of Th17 cells in experimental ence-phalitis. Thus, cathepsin K will serve as an auspicious therapeuticagent in the autoimmune arthritis by suppressing both immune re-sponses and bone resorption.

S3-1Inflammation condition clarified from effect of biologics to jointtype JIAYasuhito NeromePediatric Medical Center, Kagoshima University Hospital

　The rate of drug free remission was reported 5% in RF-posi-tive polyarticular-course JIA, 25% in RF-negative polyarticular-course JIA and 36% in oligoarthritis JIA with the traditional treat-ment. Not only clinical remission but also radiological remission isproven by biological treatments, and the possibility of the drug freeremission is being suggested. On the other hand, clinical remissionis proven in JIA, but there are little evidence of radiological remis-sion and drug free remission. There are controversial that the evi-dence of biologics in RA is applied to JIA.The clinical trial of etanercept in refractory JIA starts in 2003 in Ka-goshima University, and the clinical trial of tocilizumab starts in2004. Then, it was examined whether the rate of drug free remissonis changed after 2004. In Kagoshima University, there were 66 jointtype JIA patients had developed before 2003 (23 RF-positive , 15RF-negative, and 23 oligoarthritis) and there were 70 joint type JIApatients had developed after 2004 (37 , 16 , and 17). 21 of these pa-tients treated with biologics (14, 6 , and 1). The drug free remissionrate within five years was observed about 32% of RF-positive , 66%of RF-negative , and 58% of oligoarthritis JIA patients had devel-oped before 2003. The drug free remission rate within five years is

observed about 0% of RF-positive , 10% of RF-negative , and 32%of oligoarthritis JIA patients had developed after 2004. The biologictreatment can not improved the rate of drug free remission in JIA.　Biologics do not necessarily at least has the ability to improve therate of drug free remission in Kagoshima University. But it is neces-sary to consider the following points: this data is result of one facili-ty, a possibility to insufficient try to stop the biologics. If guidelinesto discontinued biologics provide, or the number of early-onset JIAtreated with biologics, this conclusion may be changed. 　

S3-2Pathological status of adult patients with RA learned from thebiologics therapyNorihiro NishimotoLaboratory of Immune Regulation, Wakayama Medical University,Wakayama, Japan

Rheumatoid arthritis (RA) is a common autoimmune disease inadulthood, which is characterized by joint destruction. Considerablesimilarities between adult RA and juvenile idiopathic arthritis havesuggested that study for pathological mechanism of RA is also use-ful for understanding that of JIA. Biologics targeting various mole-cules, including inflammatory cytokines such as TNF, IL-6, IL-1,IL-12, IL-15, IL-17 as well as molecules expressed on T and B cell,have been developed for RA, and they have mostly shown excellenttherapeutic efficacy with higher clinical remission rate than conven-tional DMARDs. The fact also confirmed that the target moleculesindeed play pathological roles in RA. On the other hand, they arenot always effective for every patient, or even amongst responders,the majority experience only partial improvement in disease activity.Such cases often respond to another biologic agent. Interestingly,TNF inhibition sometimes decreases IL-6 levels while IL-6 inhibi-tion also decreases TNF levels. This clearly indicates that there isnot a simple cascade but a complex network with molecular interac-tions. Indeed, we found synergistic effect between IL-6 and TNF orIL-1 in inducing VEGF and MMPs from RA synoviocytes. Thus itis required to know network regulations for better understanding ofRA pathology.DNA microarrays can be amenable to exhaustivelyanalyze the gene expressions of such multiple molecules and depictsuch network regulations of the molecules. At the symposium, in ad-dition to abnormalities in immunological networks of RA and com-parison between RA and JIA, therapeutic effect of biologics on thenetworks will be discussed.

S3-3Differences in radiographic features between two subtypes of ju-venile idiopathic arthritis: Systemic arthritis and polyarthritis

Yutaka Inaba1, Remi Ozawa2, Chie Aoki1, Tomoyuki Imagawa2,Takako Miyamae2, Masaaki Mori2, Tomoyuki Saito1, ShumpeiYokota21Department of Orthopaedic Surgery, Yokohama City University,2Department of Pediatrics, Yokohama City University

Objective: To investigate the differences in radiographic find-ings between systemic-onset juvenile idiopathic arthritis (sJIA) andpolyarticular juvenile idiopathic arthritis (pJIA).Methods: Twenty patients with sJIA and 16 with pJIA were enrol-led. Plain radiographs were obtained before the induction of biolog-ics. All radiographs were examined for the presence of soft tissueswelling, juxta-articular osteopenia, joint space narrowing, subchon-dral bone cyst, erosion, epiphyseal irregularity, growth abnormali-

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ties. Carpal length and bone mineral density of lumbar spine wereinvestigated in all the patients enrolled. We also checked for thepresence of compression fractures of any vertebral bodies. Laborato-ry examinations were involved white blood cell counts, CRP, rheu-matoid factor, and anti-CCP antibody.Results: The most frequent radiographic abnormality in sJIA wasjuxta-articular osteopenia (70.2%) in comparison to 53.5% in pJIA.Joint space narrowing was detected in 19.7% of sJIA comparable to47.7% in pJIA. Subchondral bone cyst and erosion were more fre-quent in pJIA than sJIA. Carpal length was statistically shorter inpJIA patients (p

patients with an inadequate response to MTX and/or TNF inhibitors.Efficacy of Tocilizmab is almost similar to that of TNF inhibitors.Abatacept (CTLA4-Ig) is recently approved in Japan and increasing-ly employed in the treatment of RA, particularly after TNF block-ade. The mechanism of action of abatacept may induce the T cellanergy by prevention of the two signal stimulations (TCR andCD86/86-CD28) that are required for activation of T cells. A varietyof adverse events are now recognized with reactivation of latent tu-berculosis, other pulmonary infections, interstitial pneumonia, softtissue and joint infections, concerns for lymphoma, solid malignan-cy. AE can exist in an individual patient at surgical intervention de-pend on the patients back ground and drugs including biologics andsteroid. Risk/benefit trade-offs need to take into account to make de-cisions of surgical intervention such as joint replacement. The post-operative infectious rate in joints replacements with biologic wereunder discussion. The several reports showed different results. Thesurgeon who will undertake the joint replacement should considerthe methods to facilitate intimate informed discussion with patients.

S4-2Timing of the orthopaedic surgery for RA patients using biolog-ic agentsKeiichiro Nishida1, Tomoko Kanazawa2, Ryuichi Nakahara2, KenzoHashizume2, Yoshihisa Nasu3, Taichi Saito2, Toshifumi Ozaki21Department of Human Morphology, Okayama University GraduateSchool of Medicine, Dentistry and Pharmaceutical Sciences, 2De-partment of Orthopaedic Surgery, Okayama University Hospital,3Department of Orthopaedic Surgery, Kurashiki Kosai Hospital

Biologic agents exhibit strong anti-inflammatory property andinhibitory effect against joint destruction of rheumatoid arthritis(RA). Early intensive management using these drugs made clinicalremission or bio-free remission a realistic goal, with recent revisionin dose limitation of methotrexate to match the level of foreigncountries. However, biologic agent is not always effective for RAwith high disease activity, and cannot be used for some populationof patients who experienced adverse events, or have risk factors ofthese events. Some patients cannot use biologic agents for economicreason, and other patients already show severe joint destruction orirreversible disability in physical function at the introduction of bio-logic agent. For these patients, surgical intervention is still necessaryas an adjuvant therapy.We retrospectively investigated a total of 887 elective orthopaedicprocedures for RA performed between April 2004 and December2010 at two centers (Okayama University Hospital and KurashikiKosai Hospital). 128 procedures have been done in patients usingbiologic agents. The yearly number of these cases has been increas-ing, including total joint arthropasty (44 procedures) and foe plasty(23 procedures). Basically, the operation is withheld for threemonths after introduction of biologic agents, and treatment by bio-logics is interrupted before surgery and restarted 1-2 weeks after theprocedure, on the balance of the safety of the surgery and control ofdisease activity. Introduction of biologic agent takes precedenceover surgery when healing of the joint can be expected, but surgerymay be indicated before biologics for the joint with irreversiblefunctional damage. Surgical intervention might be required for thejoints with progressive destruction and/or with insufficient effects ofbiologics. In this symposium, based on the review of our cases, wediscuss the indication and timing of the surgery for RA patients us-ing biologics.

S4-3Early Assessing of Postoperative Infection in Patients withRheumatoid Arthritis Treated with Biological AgentsJun HashimotoNHO Osaka Minami Medical Center

For early detection of surgical site infection (SSI), the surgeonsassess the laboratory test such as CRP, ESR and WBC count, feverand local symptoms and signs such as swelling, warmth, redness andpain. These could be, however, influenced by the disease activity ofrheumatoid arthritis (RA) and so the diagnosis of postoperative in-fection in patients with RA is often difficult. To the matter more dif-ficult, oral medication used quite frequently for treatment of RAsuch as glucocorticoid and methotrexate could also modify both lab-oratory and clinical findings. Moreover, recently frequently used bi-ological DMARDs could also strongly influence these findings usedfor the early detection of SSI. Therefore, it is growing more impor-tant issue how we should do for the early detection of SSI in patientswith RA. But, we have to recognize that the successful tight controlof RA with biologic/nonbiologic DMARDs eliminate the influenceof disease activity of RA on the local findings and laboratory dataused for the early detection of SSI.　So, we have to become skilledin early diagnosis of SSI in case of tightly controlled RA. On thecontrary, it could remain to be very difficult to detect the SSI in caseof RA insufficiently controlled with biologic DMARDs. It might bealso very difficult to assess SSI adequately in patients with diseaseflare-up of RA due to postponing administration of biologics for thesake of elective surgery. It is the one of reasons why we, orthopae-dic surgeons, must verify the benefit and risk of postponing admin-istration of biologics for the sake of elective surgery. On the other hand, it is ideal that we have the tool for the early de-tection of SSI never influenced by either of the disease activity ofRA, glucocorticoid and biologoc/nonbiologic DMARDs. Nishino J(2010) has already reported the usefulness of neutrophil CD64 ex-pression in the diagnosis of local infection in patients with RA, andits coming into wide use is awaited.

S4-4Histological analyses of synovium in RA treated with/without bi-ological drugs.Yuichi Mochida1, Katsushi Ishii1, Kengo Harigane1, YasushiAkamatsu2, Naoto Mitsugi2, Yuichiro Yamaguchi3, Tomoyuki Saito31Center for Rheumatic Diseases, Yokohama City University MedicalCenter, 2Department of Orthopaedic Surgery, Yokohama City Uni-versity Medical Center, 3Department of Orthopaedic Surgery, Yoko-hama City University School of Medicine

Objective: We evaluated histological findings of synovial tis-sues in rheumatoid arthritis (RA) patients treated with/without bio-logical drugs.Materials and methods: Fifty-four RA patients who underwent or-thopaedic surgery were divided into two groups. Twenty-six patientstreated with biological drugs (Group B) were compared with 27 pa-tients treated with non-biological drugs (Group C). In group B, eta-nercept, infliximab, tocilizumab, and adarimmab were administeredto 9, 8, 2 and 2 patients respectively. The synovial tissues obtainedduring surgeries were assessed using scoring system by Rooney etal., which are composed of 6 histological features: synoviocyte hy-perplasia, fibrosis, proliferating blood vessels, perivascular infil-trates of lymphocytes, focal aggregates of lymphocytes, and diffuseinfiltrates of lymphocytes.Results: The scores of focal aggregates of lymphocytes and totalscore in group B were lower than in group C. The other features,

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proliferating blood vessels and perivascular infiltrates of lympho-cytes, also showed relatively lower scores in group B.Conclusion: Our findings suggested that biological drugs have sup-pressive effects on focal aggregates of lymphocytes and total Roo-ney’s score.

S4-5Surgical site Infections in rheumatoid patients receiving biologi-cal agentsToshihito Mori, Takuo Juji, Kimio Masuda, Mitsuyasu Iwasawa,Hiroshi TakamureDepartment of Orthopedic Surgery, NOH Sagamihara Hospital, Sa-gamihara, Japan

Objective. To identify risk and surgical site infection (SSI) ratein patients with rheumatoid arthritis (RA) who had undergone elec-tive orthopedic surgery with special attention for biological agents.Methods. Preioperative and late surgical site infection (SSI) in pa-tients with RA who had undergone elective orthopedic surgery wasstudied.Results. A total of 1153 procedures were performed for the rheuma-toid patients in our hospital between January 2005 and December2010.　Ninety- nine procedures (8.6%）were performed on patientswho used Biological agents. Biological agents were stopped perio-peratively. Early deep SSI occurred in 1 patient who had undergonetotal hip arthroplasty (THA), and 1 patient who had undergone totalelbow arthroplasty (TEA). Patients that had early SSI did not use Bi-ological agents. Early deep SSI rate were 0 % (0/375), 0.7 %(1/140), and 0.8% (1/126) after TKA, THA and TEA, respectively.Early SSI did not occur in patients who used Biological DMARDs.Use of Biological agents was not associated with an increase in ear-ly SSI rates. Late deep SSI (prosthetic joint infection) occurred in 4TKAs, 1 THA and 1 MP Arthroplasty during the same period. Latedeep SSI occurred in 2 TKAs secondary to sepsis after the introduc-tion of Biological agents.Conclusion. Our study shows that early SSI rates in RA patients af-ter elective orthopedic surgery are very low. Perioperative manage-ment is an important issue in the general care of patients with RA.Patients who used Biological agents do not seem to be a strong riskfactor for SSI. Discontinued perioperative use of Biological agentsseems to be a standard management for patients with RA who hadundergone elective orthopedic surgery. Late SSI is a big concern forpatients with RA who had underground multiple surgeries and usedBiological agents.

S4-6Influence of the biologics to the postoperative rehabilitation forRA patientsRyuichi Saura1, Kazunari Tanaka1, Haruki Nakano2,3, MichiakiTakagi2,3, Isao Matsushita41Department of Rehabilitation Medicine, Division of ComprehensiveMedicine, Osaka Medical Collage, Osaka, Japan, 2Department ofOrthopaedic Surgery, Yamagata University, Yamagata, Japan, 3Re-habilitation Unit, Yamagata University Hospital, Yamagata, Japan,4Department of Orthopaedic Surgery, Faculty of Medicine, ToyamaUniversity, Toyama, Japan

Protraction of RA induces the disorders of joint function such ascontractures and deformities. As a result, activities of daily living(ADL) are deteriorated, which yields the limitation of social partici-pations. Functional disorders have once developed, a plural numberof it make disabilities worse. In present, surgical treatments for RApatients succeed in the functional recovery of the deteriorated joints

and restoring the ability of ADL. However, there are some difficul-ties in terms of the postoperative rehabilitation for RA patients. Thedysfunction of joint on contra- or ipsi-lateral side of treated joint inlower extremities might affect the progression of program due to thecontracture and the pain on motion. Also, problems in upper extrem-ities might disturb the transference in ADL and the ambulation withpartial weight bearing by crutches. In late years, it is reported thatthe quick effect characteristics and the high effectiveness of biolog-ics. When the structural remission following the clinical one hasbeen successfully introduced by the biologics, the problems con-fronting the execution of rehabilitation might be reduced. It is alsoreported that the exercise in addition to the biologics have shownbetter effects on the functional recovery of upper extremities incomparison with the biologics alone. These results might suggestthat the preoperative exercise in combination with biologics let theRA patients execute the postoperative one more easily. However,even if RA patients have achieved their clinical remissions by bio-logics, joint destruction might progress rapidly by overuse of thatjoint when it had been damaged beyond the moderate stage. It seemsthat similar troubles such as tendon rupture during exercise may beobserved in upper extremities. In conclusion, it must be emphasizedthat both the execution of more prudent postoperative and preopera-tive exercise are very important even in the time of biologics mainlyused for the treatment of RA.

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Current SymposiumCS1-1The assessment of RA patients using FDG-PETKoichi Okamura1, Yukio Yonemoto1, Kimihiko Takeuchi1,2,Masatoshi Matsushita2, Tsuyoshi Ichinose1, Tetsuya Kaneko1,Tsutomu Kobayashi1, Kenji Takagishi11Department of Orthopaedic Surgery, Gunma University GraduateSchool of Medicine, Maebashi, Gunma, Japan, 2Department of Or-thopaedic Surgery, Isesaki Fukushima Hospital

Background Positron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) could possibly evaluatemetabolic activity of synovitis and measure disease activity in rheu-matoid arthritis (RA) by whole-body imaging. 18F-FDG-PET stud-ies are proposed to assess the metabolic activity measured quantita-tively by standardized uptake value (SUV). In this study, we evalu-ated if the FDG uptake of the affected joints correlated with the clin-ical assessment of RA patients and if there were correlations be-tween the difference of SUVs and improvement of clinical findingsin the patients undergoing anti-TNF therapies. In addition, we as-sessed RA synovitis of shoulder joints with FDG-PET in compari-son with MRI. Furthermore, we examined the relationship betweenFDG-PET findings and the progress of the later joint destructions. Methods Whole-body 18F-FDG-PET were performed. Patientswere scanned from the head to the toe in the arms-down position.The increased 18F-FDG uptakes in bilateral shoulder, elbow, wrist,hip, knee and ankle joints were recorded. For the semiquantitativeanalysis, functional images of the SUV were produced and the max-imal SUV (SUVmax) was used as a representative value for the as-sessment. For the assessment of joint destruction, we reviewed SUVand changes of Larsen grade in RA patients. Results The total SUVmax significantly correlated with DAS28,DAS28-CRP, ESR, CRP and RF. ΔSUV, the difference of SUV-max-sum between before and after treatment, significantly correla-ted with ΔDAS28, ΔDAS28-CRP, ΔESR, ΔCRP and ΔRF, respec-tively.　The total number of the synovitis in the shoulder jointswere significantly correlated with SUV of the joints. The progress ofthe joint destructions significantly related to SUV.Conclusions FDG-uptake represented by SUVs in the inflamed RAjoints may reflect disease activity. FDG-PET might play an impor-tant role in the evaluation of biological treatment and the predictionof the joint destruction progress for RA.

CS1-2MR imaging of cartilage in RAAtsuya WatanabeDepartment of orthopedic surgery, Teikyo University Chiba MedicalCenter, Chiba, Japan.

In recent years, treatment strategy in rheumatoid arthritis (RA)has been dramatically improved. Early initiation of disease modify-ing ant-rheumatic drugs (DMARDs) and biological drugs requiremethods for early diagnosis and sensitive monitoring of the diseaseprocess. Blood tests can help diagnose arthritis, monitor treatments,and track disease activity, however, it could not evaluate the specificjoint status in RA. magnetic resonance (MR) imaging may be im-portant in detecting early disease manifestations in joints such as in-flammatory changes in the soft tissues and bone. However, conven-tional MRI could not quantify the change in joints associated withRA. Several qualitative MR imaging techniques have been devel-oped to monitor the cartilage matrix status. Transverse relaxationtime (T2) mapping is sensitive to the integrity of the collagen net-work structure, collagen concentration, and water concentration in

cartilage. As collagen is one of the major solid constituents of artic-ular cartilage, monitoring collagen status with T2 mapping is usefulfor determining the quality and function of cartilage. T2 mappingwas used in numerous studies that involved mainly degenerativecartilage associated with osteoarthritis (OA), and they may also havethe potential to assess the cartilage matrix status in RA patients. Asdeterioration of cartilage is observed from the early stage of RA, andit affects prognosis of joints, T2 mapping can be an ideal marker formonitoring disease activity and joint damage in RA. In this presen-tation, the ability of T2 mapping to evaluate the cartilage damageand the characteristics of cartilage degeneration in RA are discussed.

CS1-3Evaluation of rheumatoid arthritis using musculoskeletal ultra-soundYoshiaki IshigatsuboDepartment of Internal Medicine and Clinical Immunology, Yoko-hama City University Graduate School of Medicine.

Musculoskeletal ultrasound (MSUS) has been demonstrated tobe more sensitive than clinical assessment in the detection of jointswelling, and more sensitive than conventional radiography in thedetection of bone erosions. According to our survey by questionnaire, rheumatologists have in-creasingly incorporated MSUS technology into their practices andresearch during the last few years in Japan. Grey scale ultrasound is more accurately and objectively in assess-ing synovial thickness, effusion and bone erosion than clinical as-sessment. Power Doppler ultrasound has proved to be a feasible toolfor evaluating the degree of inflammation of synovial tissues (activesynovitis). It is therefore useful to evaluate the disease state of RAby MSUS for making early diagnosis and understanding the courseof the disease correctly. It’s also useful for detection of ruptured ten-don, edematous nerve, and crystal deposits in the joint with gout andCPPD disease. Recently, the utility of a power Doppler has been focused for itsability to predict joint destruction. The above including our caseswill be discussed.

CS1-4Radiographic examination for diagnosis and evaluation of rheu-matoid arthritisIsao Matsushita, Hiraku Motomura, Eiko Seki, Tomoatsu KimuraDepartment of Orthopaedic Surgery, Faculty of Medicine, Universi-ty of Toyama

Radiographic examination is an important tool to perform diag-nosis and to assess therapeutic efficacy in rheumatoid arthritis (RA),and is a gold standard among various imaging modalities. Plain X-ray examination at early stage may show soft tissue swelling andbone atropy around joints. Pocket erosion in bear areas, joint spacenarrowing and roughness of subchondral bone are detected at pro-gressive stage in RA. At the end stage, joint deformity and ankylosismay be observed. It is now also known that radiographic repaircould be recognized under good therapeutic control. Critrias ofSteinbrocker and Larsen has been useful to evaluate radiographicprogression of joint damage in RA. Larsen method judges jointdamage by 6 grades (0-V) employing standard films and is appropri-ate to assess the damage of large joints. Modified total Shrap scoreis useful method for detecting a small structural change in joint.However, only small joints in hand and feet, not large joints, are as-sessed by this scoring system. We developed ARASHI scoring sys-tem for evaluation of large joint damage in RA. This scoring system

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has status and change scoreｓ. Status score shows condition of jointdamage, and is well-related to Larsen grade. Change score indicatesprogression or repair of joint damage. The detail of large joint de-struction can be evaluated using this scoring system. We hope thatthis scoring system will become a useful evaluation to prevent theprogression of joint damage in RA.

CS1-5Current and future role of computed tomography in rheumatoidarthritisHideharu Sugimoto, Waka NakataDepartment of Radiology, JIchi Medical University School of Medi-cine

Inflammation of articular and periarticular tissues is the hall-mark of RA. In the 2010 RA classification criteria, to classify as 'de-finite RA' is based on the confirmed presence of synovitis in at leastone joint, rather than the detection of bone erosion or cortical decal-cification in the former criteria. However, skeletal destructions arethe key to the diagnosis and assessment of long-term prognosis inRA. This presentation is aim to re-acknowledge the potential role ofCT scan in RA. In RA, not only may skeletal tissues be involved at juxtarticular andsubchondral sited as marginal erosion, but also there is an evidencethat RA effects on bone remodeling that affect the entire skeleton asgeneralized osteoporosis. Further, CT has been used to validate mar-ginal erosion detected by MR imaging and US. It has also been usedto investigate generalized axial osteoporosis by means of QCT.Although, marginal erosion is not a specific finding of RA, smallerosions could be observed in healthy individuals and RA patients,whereas lesions >1.9 mm in diameter were highly specific for RA.Marginal bone erosion is still recognized as an important finding inthe 2010 RA criteria, and is described as follows; those with ero-sions typical of RA are deemed to have prima facie evidence of RAand can be classified as such.MR imaging and US can detect erosion. However, sensitivity ofthese modalities is limited compared to CT. Actually, erosions de-tected by CT are considered to be reference standard to evaluate di-agnostic accuracy of erosion in these modalities. There are, howev-er, few study on coherence in between MR/US bone erosion and CTerosion. A variety of therapeutic agents are involved in the control of boneremodeling. They include osteoprotegerin, anti-LANKL ligand anti-body, and cathepsin K. To assess therapeutic effect of these agents,CT may be used to evaluate bone formation and improvement of os-teoporosis.

CS2-1The window of opportunity for drug therapy and surgical inter-vention for RADaisaku Tokunaga, Ryo Oda, Toshikazu KuboDepartment of Orthopaedics, Graduate School of Medical Science,Kyoto Prefectural University of Medicine

Recent developments in drug therapy with methotrexate and bi-ological agents have provided great benefit to patients with rheuma-toid arthritis (RA) by reducing joint inflammation and pain. In therecommendations for achieving optimal therapeutic outcomes in RApublished in 2010, it is stated that the primary target for treatment ofrheumatoid arthritis should be a state of clinical remission, in thestrategy of ten treat to target (T2T) activities. In order to alter thenatural history and accomplish remission of the disease, early diag-nosis and aggressive therapy during the ‘window of opportunity’ is

necessary. The surgical therapy for rheumatoid arthritis has there-fore been changed both quantitatively and qualitatively. The num-bers of the patients who require surgical therapy decreases with age.However, for the patients with established joint destruction and forthose who are not able to undergo radical drug therapy, surgicaltherapies should be recommended. In addition，biological agents donot necessarily induce remission of the disease. Despite the fact thatadequate disease control is often established by biological agents,some cases show rapid joint destruction of limited area of joints, es-pecially in the hands and weight bearing joints. In fact, the rapid im-provements in the quality of life and ability of daily living due to thepharmacotherapy may further increase the load on the already frag-ile joint, resulting in the aggressive joint destruction. Therefore,careful evaluation of not only parameters such as DAS28, CDAI andSDAI, but also close evaluation of each joint, should be performed.Currently, total hip arthroplasty is often performed for patients withRA. It is desirable to plan surgery before shortening of the lowerlimb by joint destruction and bone loss of the acetabular joint. It istherefore of high importance to determine individual articular prog-noses, and to implement an appropriate surgical plan for individualpatients.

CS2-2Significance of Hip Surgery for RA Patients in the Era of Bio-logics TherapyNaoto Mitsugi1, Kengo Harigane1, Katsushi Ishii1, Yuichi Mochida1,Naoya Taki1, Yuichiro Yamaguchi2, Tomoyuki Saito2, Izumi Saito3,Shigeki Momohara4, Kosei Kawakami4, Katsunori Ikari41Yokohama City University Medical Center, Yokohama, Japan,2Dept. of Orthpaedic Surg., Yokohama City University School ofMedicine, 3Yokohama Municipal Hospital, Yokohama, Japan, 4Insti-tute of Rheumatology, Tokyo Woman`s Medical Unversity, Tokyo,Japan

(Backgrounds) Biological agents therapy provides great benefitto rheumatoid patients. In Europe and United States, there are sever-al reports of decreasing in rates of orthopedic joint surgery for rheu-matoid arthritis. Although, in Japan, decrease of some kind of sur-gery for example knee synovectomy was reported, it is uncertainwhether total numbers of orthopedic surgery for rheumatoid arthritisdecrease or not. In this study, it will be investigated for hip surgeryfor rheumatoid arthritis in the age of biologics therapy.(Material and Methods) Rheumatoid Patients who underwent THAin Yokohama City Universal Medical Center and Institute of Rheu-matology, Tokyo Woman`s Medical University were analyzed. Thepatients were classified into a biologics therapy group and non bio-logics group. Complication of surgery, periods of hospitalization,course after surgery were examined.(Results) The total numbers of yearly THA were stable from 2000to 2010. The numbers of the patients who underwent THA with bio-logics therapy was 17. In this group, there was no findings of surgi-cal site infection and delayed wound healing.(Discussion) There was no decrease in total numbers of rheumatoidhip surgery. In this study, There is no surgical complication in THAwith biologics therapy. Since the sample size was small, it is neces-sary that bigger sample study should be performed.

CS2-3Mid term results of total hip arthroplasty in patients with rheu-matoid arthritisShu Saito

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Department of Orthopedic Surgery, Nihon University School ofMedicine, Tokyo, Japan

We reviewed 58 cementless total hip arthroplasties (THAs) in39 patients with rheumatoid arthritis (RA) at an average follow-upof 9.6(5-18) years. Preoperatively, 19 joints had a protrusio acetabu-li of grade I or higher (Sotelo-Garza-Charnley classification). We re-constructed THA in cases with protrusio acetabuli with morsellizedand sliced autologous bone grafts from the femoral head. Postopera-tively, 29 joints were rated excellent; 23, good; 6, fair (Harris hipscore). There was no thigh pain and deep infection. There was an in-traoperative fracture of the femur in one joint. Radiography showedthat the acetabular component was stable in 56 joints, and possiblyunstable in 2 joints. The femoral component was bone-ingrown in54 joints, and stable fibrous in 4 joints. Postoperatively, we ob-served dislocation in 4 joints, and disuse atrophy of the femur in 4joints. There were no clear signs of loosening, migration or osteoly-sis at an average follow-up of 9.6 years and no patients required re-vision surgery. These results indicate that the cementless THA hadexcellent mid-term outcome and the current method with morsel-lized and sliced autologous bone grafts is extremely useful in caseswith protrusio acetabuli in hip joints for the treatment of RA.

CS2-4Selection of Components in Total Hip Arthroplasty for Rheu-matic PatientsHideo Okumura, Norikazu Takeda, Kenzou Fuse, Kenji MatsumotoOrthopaedic Surgery, Rakuyo Hospital, Kyoto, Japan

The treatments of rheumatic patients have been much improvedby development of biological drugs, and the destruction of the jointshas been prevented. However, total hip arthroplasties ( THA ) arenecessary in the patients with severely destructed hip joints. Theclinically affected factors of THA for rheumatic patients are infec-tion under immune abnormality, steroid administration, osteoporo-sis, muscle weakness and dislocation. Many components have beendeveloped and useful. Each component has each characteristic. Twopoints of view are there, quality of bone tissue and complications inthe selection of components.Selection of components according to quality of bone tissue : Com-mon THAs have been done in the almost normal and not destructedhips. The most important thing is initial fixation of the component inboth cement fixation and cementless fixation. In the case of cementfixation, the cement technique must be sufficiently practiced. Pres-surizing of cement is especially important. Flange socket in acetabu-lum and the stem with smooth surface in femur must be selected. Inthe case of severely destructed hip joints, some support rings or KT-plate must be used. In the case of very thin cortical femur, impactionbone grafting and the stem fixed with screws are useful.Selection of components according to complications : Antibiotic-contained cement is useful for the prevention of infection. To pre-vent the dislocation, the components with thin neck and the stemwith large offset must be used. Cross-linked polyethylene and largehead are useful in the prevention of dislocation. Summary : Detailed preoperative planning and careful selection ofcomponent are very important in total hip arthroplasty for rheumaticpatients. The components must be selected according to quality ofbone tissue and complications.

CS2-5Methods for reconstruction in THA revision using allograftbones on rheumatic jointsNaonobu Takahira1, Katsufumi Uchiyama2, Kensuke Fukushima2,Tadashi Kawamura2, Mitsutoshi Moriya2, Masashi Takaso2,Moritoshi Itoman31Department of Rehabilitation, Kitasato University School of AlliedHealth Sciences, Kanagawa, Japan, 2Department of OrthopaedicSurgery, Kitasato University School of Medicine, Kanagawa, Japan,3Kyushu Rosai Hospital, Fukuoka, Japan

【Acetabular side】 In THA revisions, restoring bone defects onthe damaged acetabulum is required to ensure strong primary fixa-tion to host bone. Itoman classification characterizes bone loss onthe acetabular side: Type A　(lateral defect) includes osteoarthritisof the hip secondary to dysplasia, rapidly destructive coxarthrosis(RDC) and loosening of the artificial joint. Type B (central defect)includes protrusio acetabuli in rheumatoid arthritis (RA) and centralmigration of hemiathroplasty. Type C (cranial defect) includesRDC. Type D (cranio-central defect) includes loosening of the ce-mented cup or high hip center cup, or progression of RA bone de-struction. It is important to determine the exact location and extentof bone loss prior to surgery and reconstruct the hip joint center po-sition at the original site. Type B and C allow reconstruction withallograft bone using a support ring. Type D utilizes the addition ofstrut screws.【Femoral side】 Reconstruction of the femur requires different allo-genic bone depending of the degree of bone loss. Gustilo classifica-tion is used to categorize bone loss into Types I-IV. Defects areclassified by degree of bone loss and loosening. Gustilo Types I, IIor unclassified cases allow the use of morselized allogenic grafts orchipped bone to fill defects. Type III allows cortical struts to be em-ployed at the site of calcar defect. Type IV also allows reconstruc-tion with a segmental cortical allograft.Drawbacks of allogenic grafting include a longer time comparedwith autologous bone for incorporation and firm initial fixation, theneed for bone banking, and transmissible disease risk. Benefits in-clude securing of bone stock　and a priori preparation of necessaryamounts of bone.

CS2-6Hybrid THA after the operation to rheumatoid arthritisTamotsu Okuaki, Kazuaki Tsuchiya, Toshinao Fukuda, MasatoSonobe, Tatsuro Sakurai, Toru SuguroDepartment of Orthopaedic Surgery, Toho University School ofMedicine

Occasions to perform THA for hip disorder in RA are not infre-quent. We used hybrid THA to RA. In this study, we report our con-sideration of cases which were more than ten years post-operation.The subjects were 54 cases/79 joints who had hybrid THA for hipdisorder of RA since 1992, and the average age at operation was63.2 years.The average follow-up term was 17 years and 4 months.Clinical evaluation of these cases was made by JOA Score, and radi-ological evaluations were made, on the socket side by the change ofthe abduction angle with time with and without bone transplant andby the frequency of occurrence of clear zones by Delee’s method,and on the stem side by the relationship between the cementingtechnique and the grade and by the frequency of occurrence of clearzones by Gruen’s method. The JOA Score improved significantlycompared to the pre-operative score. On the socket side, no signifi-cant change with time of the abduction angle was seen with or with-out bone transplant. The greatest occurrences of clear zones were in

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zone II. On the stem side, there were more cases of cementing gradeA for the second compared to the first generation cementing techni-que. The greatest occurrences of clear zones were in zones I andVII, and on the central side, regardless of the grade. Also, occurren-ces in zones III and V for grade B or lower were greater comparedto grade A. Re-implantations were required in 8 joints. Causes forthis included loosening, and wear of polyethylene. The survivalcurve by the Kaplan-Meier method with the time of re-implantationas the end point indicated 89.9% at 18 years. The long-term post-op-erative outcome of hybrid THA for RA was considered. Stable out-comes were obtained and it was considered that hybrid THA for RAis a useful operative procedure.

CS3-1Prevention and control of infection under the treatment with bi-ologicsToshihiro MatsuiDepartment of Rheumatology, Sagamihara National Hospital, Na-tional Hospital Organization, Kanagawa, Japan

Infection is one of the frequent and important complications inpatients with rheumatoid arthritis (RA). Their risk of infection is in-creased twofold compared with non-RA subjects (Arthritis Rheum2002;46:2287-93), and increasing age, comorbidities and use of cor-ticosteroids are strong predictors of infection in RA (ArthritisRheum 2002;46:2294-300). Biologic therapy has led to remarkablepatient benefit in recent years; however, it also increased the risk ofinfection in patients with RA (JAMA 2006;295:2275-85, et al.). Forthe maintenance of efficient treatment with biologics, preventionand control of infection is essential.Prevention and control of infection under the treatment with biolog-ics in patients with RA are very important and sometimes difficult inthe conditions, such as 1)screening and prevention of infection be-fore starting treatment with biologics, 2)monitoring and preventionof infection during the treatment with biologics, 3)quick and ade-quate response against infection, 4)decision to resume biologics af-ter recovery from infection, and 5)decision to resume biologics ormonitoring of infection after surgical procedure. In this presentation,we summarize the data published so far and our efforts about pre-vention and control of infection.We have reported the utility of neutrophil CD64 in RA as an infec-tion marker which is less affected with the disease activity of RA it-self (J Rheumatol　2006;33:2416-24, J Orthop Sci 2010;15:547–552). Neutrophil CD64 is useful for screening, monitoring, and earlydetection of infection and can be effective even under the treatmentwith tocilizumab (Mod Rheumatol 2009;19:696-7). Of course, histo-ry taking, physical examination, and education of patients and theirfamily are more important for detection of infection; however, infec-tion markers, such as neutrophil CD64, should be more utilized as asupportive tool for monitoring and early detection of infection.

CS3-2Pneumocystis pneumoniaHideto KamedaSchool of Medicine, Keio University

Acute-onset diffuse interstitial lung diseases (AoDILD) in pa-tients with rheumatoid arthritis (RA) has been a serious concern, es-pecially for those under treatment with biological agents which mayaffect the presentation and outcome of AoDILD. A retrospective,multi-center study of AoDILD in RA patients receiving biologicalagents (infliximab, etanercept, adalimumab and tocilizumab) hasdemonstrated the importance of Pneumocystis pneumonia (PCP)

among AoDILD in those patients. In that study, definite PCP wasdefined as patients who showed either P. jirovecii organisms in theirrespiratory samples by microscopic examination, or positive testsfor both P. jirovicii DNA-PCR with respiratory samples and an ele-vated serum 1,3-β-D-glucan level above the cut-off value. Andprobable PCP was defined as either a positive test for P. jiroviciiPCR or an elevated serum β-D-glucan level. Chest HRCT findingswere evaluated and scored by two board-certified radiologists. Thefinal diagnoses for 26 patients examined were definite PCP for 13patients, probable PCP for 11, and methotrexate-associated pneumo-nitis in 2 patients. Definite and probable PCP cases were clinicallyindistinguishable. Generalized, diffuse ground-glass opacity (GGO)is the characteristic HRCT finding in patients with definite or proba-ble PCP, which was different from our previous findings in RA pa-tients, mostly without biologics, showing GGO distributed in a pan-lobular or multilobular manner. The clinical outcome was favorableby treatment with trimethoprim-sulfamethoxazole (TMP/SMX) andglucocorticoids. However, adverse events with TMP/SMX such asgastrointestinal and hematological disorders were commonly ob-served at an approximate rate of two-thirds in the patients. Conse-quently, more than one-third of the patients could not completeTMP/SMX treatment. Taking this fact and less organism burdenthan AIDS-PCP into consideration, a reduced dose of TMP/SMXmay be sufficient for RA-PCP patients with biologics.

CS3-3Treatment of nontuberculous mycobacteriosisAtsuyuki KurashimaJapan Anti Tuberculosis Association Fukujuji Hospital

TNF is an essential cytokine that confine tuberculous lesion withgranuloma formation. Thus administration of TNF-blocker may leada danger of spreading mycobacteria through the disintegration ofgranuloma. In Japan, 15 TB cases out of 5000 Infliximab treated ca-ses were reported (about 15 times higher compared with generalpopulation). But attention related nontuberculous mycobacteriosis(NTM) has been focused in recent years. Okubo reported theworld’s first case of pulmonary mycobacterium avium disease withInfliximab treatment at Modern Rheumatology in 2005. Winthropcollected 105 NTM cases with TNF-blocker treatment includingJapanese 12 cases from all over the world. These data reveal 9 deathcases and 54% cases of extra pulmonary lesions. Today, NTM lungdisease in non-compromised host has been increased in many devel-oped countries. The estimated prevalence of this disease in Japansince 2007 is over 5.7 and it seems highest level internationally.Nowadays, more than 150 nomenclatures are registered as NTMspecies , but the distribution of them shows very differently bycountry. In Japan, mycobacterium avium complex dominate (about80%) over other species, and the upward trend of the nodular bron-chiectatic type lung disease in elderly woman has been noticeable.Most difficult problems are that there are no bactericidal drugs orcombination chemotherapies, and in vitro susceptibility dose notmatch the clinical efficacy, so the drug selection for the present spe-cies only depends on the clinical experiences accumulated for eachspecies. The appropriate chemotherapy may become a status of cer-tain improvement, but it needs a long period often exceed one ortwo years.IThis disease frequently overlap population group predi-lection of RA.From these issues, corresponding to NTM with TNF-blocker is much more difficult than that of tuberculosis.

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CS3-4Epidemiology and measures of surgical site infection followingarthroplastyToshinori Masaoka, Kosuke Kubo, Kengo YamamotoDept. of Orthopedic Surgery, Tokyo Medical University

Quality of life (QOL) of the patients suffering from joint diseasehas been remarkably improved with development of arthroplastyand its popularity. However, there is always a risk of surgical siteinfection which can be considered as one of the critical complica-tion. Because the large foreign object is inserted into the body in ar-throplasty, it is obvious the operation has a high risk of the seriousinfection. With this in mind, we consider extreme perioperative careshould be taken.The research by The Japanese Orthopaedic Associa-tion reported that operative infection rate following arthoplasty was1.3% and listed its risk factors as follows: Sexuality (male), weight,disease (tumor), complicating diseases (diabetes, osteoporosis, im-mune disorders), antibiotics use within 3 months preoperatively, his-tory of preoperative steroid injection, low in protein and/or in albu-min, years of operative experience of the surgeon, type of prosthe-sis, use of bone cement, allogeneic bone transplantation, operationtime, blood loss, allogeneic transfusion, the use of pulsing irrigation,use of double surgical suit, preoperative hospitalization period, andantibiotics infusion period after the operation.Rheumatoid arthritis isreportedly considered as one of the risk factor of arthroplasty, be-cause it causes skin fragility, and immunosuppressive drug is usedfor its treatment, though, JOA research found the infection rate inrheumatoid arthritis patients was 1.4%, which was not significantlydifferent compared to the rate in the patients with other diseases.Some studies showed TNF inhibitor raised postoperative infectionrate in rheumatic patients. Currently, there has been no reportreached a firm conclusion regarding TNF inhibitor effect on the in-fection. Since TNF-α plays an important role in infection defense,there is a concerns to the use of the inhibitor which may cause post-operative infection, and we consider further research on TNF inhibi-tor effect might be needed.

CS3-5Influence of biologics for spinal surgeryHiroshi Takahashi, Akihito Wada, Ayako Kubota, YuichiroYokoyama, Fumiaki Terajima, Keiji Hasegawa, Takashi Saito,Takashi Arai, Toru SuguroToho University School of Medicine, Department of OrthopaedicSurgery

ObjectiveIn recent years, biologics such as TNF-a inhibitors (infliximab andetanercept) and an IL-6 receptor antibody (tocilizumab) have beenused to treat rheumatoid arthritis(RA). However, the effects of thesebiologics on postoperative complications have not been studied.Therefore, we examined complications in a group of patients afterspinal surgery.Subjects and MethodsThe subjects were 59 patients with RA who underwent surgery after2001. Among the subjects, 48 did not take a biologics, while 1 re-ceived tocilizumab and 10 took etanercept. The patient who took to-cilizumab and those treated with etanercept underwent surgery onday 22 and from days 8 to 14, respectively, after the final drug ad-ministration. The same protective antimicrobial agent was adminis-tered postoperatively in all 59 patients, in accordance with ourstandard medication manual. Wound healing and surgical site infec-tion (SSI) were examined in all subjects.Results

Prolonged wound healing was observed only in the patient treatedwith tocilizumab. SSI was not detected in any of the 59 patients.DiscussionThe effects of biologics on postoperative complications are unclear.Prolonged wound healing observed in the patient who received toci-lizumab was induced by pressure exerted on the wound site due toan unfavorable body position; therefore, the wound site was suturedagain under local anesthetic and the body position was changed fre-quently, resulting in rapid recovery. Thus, we cannot be certain thatthis complication was associated with the biologics. However, thefindings of the study suggest that unexpectedly few complicationsdevelop when spinal surgery is performed within an appropriate pe-riod after final biologics administration. Evaluation of data for morecases is required to confirm these findings.

CS3-6Infection and Infecting Organisms associated with RheumatoidArthritis Patients-Effective Treatment and Infection ControlMeasures from Standpoints of Characteristics of Pathogens-Kazuhiro TatedaDepartment of Microbiology and Infectious Diseases, Toho Univer-sity School of Medicine, Tokyo

It is well known that rheumatoid arthritis (RA) patients are sus-ceptible to several infectious diseases. Particularly, RA patients re-ceiving biologic agents, such as infliximab and etanercept, weretend to be suffered from bacterial pneumonia. Those patients weresusceptible to a variety of respiratory pathogens including Legionel-la spp, Streptococcus pneumoniae and Staphylococcus aureus, inaddition to Mycobacterium tuberculosis and Pneumocystis jirovecii.In this presentation, the important pathogens for RA patients will bereviewed in their bacteriological characteristics, simultaneously witheffective treatment and infection control measures. Especially, top-ics and some pitfalls of above organisms will be briefly discussed.In addition, appearance and spreading of antibiotic resistant organ-isms, in particular community-acquired methicillin-resistant S. aur-eus (CA-MRSA), will be focused. CA-MRSA is known to be acause of necrotizing pneumonia and refractory soft-tissue infections,even in healthy individuals. Other important antibiotic-resistant or-ganisms include multiple-drug resistant Pseudomonas aeruginosaand Acinetobacter baumanii in patients with ventilator and post-op-erative situations. In particularly RA patients after operation for syn-thetic bones and joints, biofilm formation by bacteria is a criticalfactor for treatment failure and prognosis of patients. Bacterial willform microcolony on surfaces of artificial materials that frequentlydemonstrate tolerance to antibiotic killing effects and resistant tohost anti-bacterial defenses. Hot to cope with biofilm-forming bacte-ria and prevention of biofilm is the most crucial factor for those pa-tients with transplantation of synthetic medical devises in RA pa-tients. Recently, the new insight was reported in biofilm researchdemonstrating that bacteria are communicating each other by pro-duction of small molecules named autoinducers, which enabled bac-teria regulate and coordinate virulence factors expression and bio-film formation. This new critical mechanism was referred to quo-rum-sensing in bacteria. In this presentation, several topics of im-portant organisms for RA patients, especially bacteriological charac-teristics, pathogenesis of infection and biofilm formation, in additionto effective antibacterial chemotherapy and infection control meas-ures will be presented and happy to discuss with audiences.

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CS4-1Disease-specific iPS cells for modeling of autoinflammatory syn-dromesK Megumu SaitoCenter for iPS cell research and application (CiRA), Kyoto Univer-sity, Kyoto, Japan

Besides for regenerative medicine, human induced pluripotentstem (iPS) cells, developed by Dr. Shinya Yamanaka, et al., are alsoan attractive technology for accelerate disease understanding anddrug innovation. It has been difficult for investigators to perform ex-periments with patient-derived tissues or cells because of unavaila-bility or poor reproducibility. However, by using iPS cells, thisproblem can be overcome. Now you can obtain cells for iPS-cellgeneration from patients at the bedside, then differentiate them intocells of interest and perform investigation at the lab bench, and fi-nally bring the results back to the bedside. In this presentation, I willintroduce our current study on disease modeling by using patient-specific iPS cells, and discuss future perspectives.

CS4-2Rheumatoid arthritis and osteoimmunologyTomoki Nakashima1,2,3, Hiroshi Takayanagi1,2,31Department of Cell Signaling, Graduate School of Medical andDental Sciences, Tokyo Medical and Dental University, Tokyo, Ja-pan, 2Japan Science and Technology Agency (JST), Explorative Re-search for Advanced Technology (ERATO) Program, TakayanagiOsteonetwork Project, 3Global Center of Excellence (GCOE) Pro-gram, International Research Center for Molecular Science in Toothand Bone Diseases

The interaction between the immune and skeletal systems haslong been acknowledged, but investigation into rheumatoid arthritis(RA) as well as the various bone phenotypes found in mice deficientin immunomodulatory molecules has highlighted the importance ofthe dynamic interplay between the two systems. This has led to therecent emergence and subsequent rapid evolution of the field of os-teoimmunology. In the bone destruction associated with RA, IL-17-producing helper T cells (Th17) play a major role by inducing re-ceptor activator of nuclear factor-κB ligand (RANKL). RANKLstimulates osteoclastogenesis through nuclear factor of activated Tcells cytoplasmic 1 (NFATc1), which is well known as a crucial reg-ulator of immunity. In addition to cellular interactions via cytokines,the immune and skeletal systems share various molecules, includingtranscription factors, signaling molecules and membrane receptors.The scope of osteoimmunology has grown to encompass a widerange of molecular and cellular interactions, the elucidation ofwhich will provide a scientific basis for future therapeutic ap-proaches to diseases of both the immune and skeletal systems.

CS4-3Divergent Roles of Smads in Arthritogenic T Helper 17 CellsMizuko MamuraLee Gil Ya Cancer and Diabetes Institute, Gachon University ofMedicine and Science, Korea

Transforming growth factor-β (TGF-β) is a pivotal cytokine toinduce interleukin 17-producing T helper cells (Th17), which playpathogenic roles in murine collagen-induced arthritis (CIA). On theother hand, TGF-β is known to be the most potent immunosuppres-sive cytokine to inhibit the differentiation and functions of inflam-matory effector cells as well as to induce Foxp3+ regulatory T cells.

However, the molecular mechanisms of complex functions of TGF-β remain unknown. We found that TGF-β receptor-activated Smads (R-Smads), Smad2and Smad3 exerted the opposing effects on Th17 differentiation andthe pathogenesis of CIA. Smad2 deficiency attenuated CIA by sup-pressing Th17, whereas Smad3 deficiency exacerbated CIA by en-hancing Th17. Notably, Smad2 and Smad3 acted on Stat3 activationin Th17 development through distinct mechanisms despite their highhomology. Smad2 bound with Stat3 to enhance transcription ofIL-17A and RORγt, whereas Smad3 targets transcription of JAK/STAT inhibitors, such as SOCS3 and SHP1/2 to regulate phosphor-ylation of Stat3. Divergent functions of Smad2 and Smad3 in Th17 regulation implythat the functional complexity of TGF-β is intrinsic to its canonicalsignaling pathway and R-Smads could be possible therapeutic tar-gets for rheumatoid arthritis (RA).

CS4-4A "two-receptor" model: integrins and growth factor receptorsJun Saegusa1,21Department of Clinical Pathology and Immunology, Kobe Univer-sity School of Medicine, Kobe, Japan, 2Department of Evidence-based Laboratory Medicine, Kobe University School of Medicine,Kobe, Japan

Fibroblast growth factor (FGF) and insulin-like growth factor(IGF) play important roles in the pathogenesis of rheumatoid arthri-tis because they have growth-promoting and anti-apoptotic effectson synoviocytes, and are also involved in the angiogenesis in in-flamed synovial tissue.Integrins are a family of αβ heterodimeric transmembrane moleculesthat mediate cell-extracellular matrix and cell-cell adhesion. Grow-ing evidence suggests that integrins mediate signal transductionthrough interaction with multiple cellular or extracellular matrix li-gands. FGF and IGF act through binding to the FGF receptors (FGFR) andIGF receptors (IGFR), respectively. It had been proposed that cross-talk between “outside-in” integrin signaling and FGFR/IGFR signal-ing plays a critical role in FGF/IGF signaling, but the specifics ofthe cross-talk was unclear. By using docking simulation and muta-genesis, we found that both FGF-1 and IGF-1 directly and specifi-cally bind to integrin αvβ3. In both cases, the ternary complex of in-tegrin αvβ3−FGFR−FGF-1 or integrin αvβ3−IGFR−IGF-1 wasformed. Interestingly integrin-binding-defective mutants (FGFR50Eand IGFR36E/R37E) showed markedly reduced ability to induce cellproliferation and migration, whereas they bind to FGFR/IGFR. In-vestigations on cell signaling revealed that FGFR50E did not inducesustained ERK activation, and IGFR36E/R37E did not induce IGFRphosphorylation.Taken together, our results generated an alternative evidence of therole of integrin αvβ3 in FGF and IGF signaling, in which FGF-1 andIGF-1 directly bind to integrin αvβ3 in addition to FGFR/IGFR oncell surface. It has been traditionally believed that the binding ofFGF to FGFR or IGF to IGFR is sufficient to induce cell prolifera-tion. However we have demonstrated that the simultaneous bindingof FGFR/IGFR and integrin αvβ3 to FGF-1/IGF-1 occurs duringFGF/IGF signaling. We propose this novel concept as a “two-recep-tor” model.

CS4-5Synoviolin and Rheumatoid arthritisNaoko Yagishita1, Toshihiro Nakajima2

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1Institute of Medical Science, St. Marianna University School ofMedicine, 2Institute of Medical Science, Tokyo Medical University

The symptoms of rheumatoid arthritis (RA) are based on themany processes; chronic inflammation, overgrowth of synovialcells, bone and joint destruction and fibrosis. To clarify the mecha-nism of outgrowth of synovial cells, we carried out immunoscreen-ing using anti-rheumatoid synovial cell antibody, and cloned ‘Syno-violin’. Synoviolin was highly expressed in the rheumatoid synovi-um, and confirmed that this molecule is one of the causative factorsof arthropathy. Further analysis using gene targeting approachesshowed that in addition to its role in RA, Synoviolin is essential forembryogenesis. Synoviolin deficient mice (syno-/-) exhibited severeanemia caused by enhancement of apoptosis in fetal liver, and theresults suggested that the liver is sensitive organ for Synovio-lin.Next, to understand the role of Synoviolin in fibrosis, we ex-plored the involvement of Synoviolin in liver fibrosis because ofsimplicity of its development. We applied the CCl4-induced hepaticinjury model to synoviolin heterozygote (syno+/-) mice, and demon-strated that these mice are resistant to onset of liver fibrosis. This re-sult suggests that Synoviolin is involved in not only overgrowthprocess of synovial cells but also fibrosis process.

CS5-1Validation of 2010 ACR/EULAR classification criteria for RAusing five cohortsMasayoshi Harigai1,2,7, Yuko Kaneko3,7, Atsushi Kawakami4,7,Shigeto Tohma5,7, Ayako Nakajima6,71Department of Pharmacovigilance, Graduate School of Medical andDental Sciences, Tokyo Medical and Dental University, 2Depart-ment of Medicine and Rheumatology, Graduate School of Medicaland Dental Sciences, Tokyo Medical and Dental University, 3Divi-sion of Rheumatology, Department of Internal Medicine, Keio Uni-versity School of Medicine, 4Unit of Translational Medicine, De-partment of Immunology and Rheumatology, Nagasaki GraduateSchool of Biomedical Sciences, 5Sagamihara National Hospital, Na-tional Hospital Organization, 6Institute of Rheumatology, TokyoWomen’s Medical University, 7The committee on the evaluation ofnew diagnostic criteria for RA of Japan College of Rheumatology

Advances in the treatment of rheumatoid arthritis (RA) compel-led the European League Against Rheumatism (EULAR) and theAmerican College of Rheumatology (ACR) to develop new, recent-ly published, classification criteria for RA. The aim of the new clas-sification criteria is to identify patients with newly developed arthri-tis for whom the risk of symptom persistence or structural damage issufficient to be considered for intervention with disease-modifyinganti-rheumatic drugs (DMARDs). In addition to those newly pre-senting patients, the application of the criteria to patients with ero-sions typical for RA or with longstanding disease was also consid-ered and defined. The JCR committee for evaluation of the 2010ACR/EULAR classification criteria installed a working group forcohort analysis and ordered the validation of the new criteriathrough an analysis of five cohorts in Japan; the SAKURA cohortfrom Keio University (analyzed by Y. Kaneko), the Nagasaki earlyarthritis cohort from Nagasaki University (analyzed by A. Kawaka-mi), the IORRA cohort from Tokyo Medical and Dental University(analyzed by A. Nakajima), the SACRA cohort from SagamiharaNational Hospital, National Hospital Organization (analyzed by S.Tohma), and the REAL cohort from Tokyo Medical and Dental Uni-versity (analyzed by M. Harigai). Thus far, findings of these analy-ses have revealed that sensitivities of the new criteria were distrib-uted from ~60 to ~80%, and specificities were ~60 to ~70%. Classi-

fication values of the new criteria are strongly affected by the inclu-sion and exclusion criteria, the definition of the gold standard forRA, and percentages of patients with erosions typical for RA orlong-standing diseases. We have to take these conditions into ac-count to fully evaluate the results of the validation and to apply thecriteria to the clinical diagnosis of RA.

CS5-2From expert validation group perspective - analysis summaryHisashi YamanakaInstitute of Rheumatology, Tokyo Women's Medical University

【Purpose】To validate the new RA classification criteria byACR/EULAR.【Methods】JCR committee for validation of the newcriteria by experts was organized by 10 rheumatologists in universi-ty hospitals (4), general hospitals (4) and private clinics (2), inclu-ded equal numbers of internists and orthopedists. Committee mem-bers evaluated independently the 56 case scenarios established bycohort analysis group, and recorded the likelihood for RA from 1(the least likely) to 10 (the most likely) together with the occasion toprescribe methotrexate.【Results】Among 56 case scenarios, 45 caseswho are available to score by new/old criteria were analyzed. Thosecases included 26 cases with RA as the final diagnosis, and 19 withnon-RA (SLE 4, UA 4, PsA 2, RS3PE 2, SjS 2, gout, OA, PM, sar-coidosis and PR 1). 28 females and 10 males, average age 51.1 +15.4 years old, (21−80), disease duration was 12.4 + 19.4 months(0.1−63 months). Sensitivity and specificity of the new criteria bythe final diagnosis were 53.8% and 63.1%, whereas those of 1987criteria were 23.1% and 63.1%, respectively. False positive cases bythe new criteria were 2 SLE, one each with SjS, RS3PE, PsA andPR. Correlations between scores of the new criteria and the likeli-hood for RA were R2=0.3027 in RA and R2=0.03 in non-RA. Like-lihood distributed widely among committee members, but no rela-tionship was found between subspecialty or the hospital they be-longs. Methotrexate was recommended in 48 occasions (13.8%),and the sensitivity and the specificity of this criteria for MTX usewere 72.9% and 61.8%.【Discussion】This study was conducted us-ing case scenario documents, thus, we should consider whether thismight be relevant to the real world events or not, nonetheless, ourfindings indicated the new criteria are valid to apply in daily clinicalsettings.【Conclusion】New criteria can be used in daily practice inJapan, however, we should be careful that this will not certificate thediagnosis of RA.

CS6-1Influence of organ comorbidities on therapeutic course in pa-tients with RA.Yoshie Kusunoki, Hirahito Endo, Shinichi KawaiToho University Omori Medical Center

Recently therapeutic goal of rheumatoid arthritis (RA) is a re-mission by useful therapeutic tools, biologics such as anti TNF ther-apy. But in RA patients with functional impairments needs surgeryfor functional recovery. Recently rheumatic medical care was donein the Rheumatic Center. We also do rheumatic medical care in thecollaborative relationship that orthopedics, internal medicine aremutual as rheumatic collagen disease center in this hospital. Becausesome therapeutic stances for RA being different in each specialists,it is difficult to decide allotment of a role in rheumatic medical care.RA patients usually had multiple organ complications as well as or-thopedic disorders. Several organ complications might influencemethods and how to lead orthopedics therapy. To evaluate the com-plications to influence RA therapy, we analyzed the frequency of

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other complications, cardiovascular disorders, respiratory disorders ,and metabolic disorders using Charlson Comorbidity Index(CCI) inour hospital. Previous report show that RA having a complicationoccupies higher than half in the RA patient in the department con-cerned, a complication need for therapy of internal medicine wasfound in 54% of patients with RA. It was hypertension 27.9%, dia-betes mellitus 12.3%, hyperlipemia 11.7%, respiratory tract disease7.5%, cardiovascular disease 6.6%, and malignant tumor 6.6%. Or-gan involvements have an influence on a function of the patient re-gardless of disease activity of RA by a case. We report cooperationto aim at thought patient QOL amelioration on collaborative rela-tionship of internal medicine and orthopedics in a RA medical caresystem.

CS6-2Joint replacement when using biologic agents in the patientswith rheumatoid arthritisAyako Kubota1, Toru Suguro1, Masayuki Sekiguchi11Department of Orthopaedic Surgery, Toho University School ofMedicine, 2Tsuchida clinic

The drug therapy for rheumatoid arthritis (RA) has dramaticallyimproved the outcomes with the advent of methotrexate and biolog-ics. In our hospital, the drug therapy for RA is performed in bothDepartments of Rheumatology Center and Orthopedic Surgery.Some reports have indicated a decrease in the number of orthopedicoperations due to biologics; however, the operations which use bio-logics have increased at our department since 2006. RA patients on whom the Department of Internal Medicine requestsus to perform operations account for many cases of advanced bone destruc