ISSUE 4 YEAR 2 NOVEMBER 2011

ACR 2011: HIGHLIGHTSBasic ResearchRheumatoid ArthritisSpondyloarthritisConnective Tissue Diseases

VasculitisImagingOsteoarthritisFibromyalgiaMetabolic & Crystal ArthropathiesOsteoporosis & Metabolic Bone Disease

Dear young rheumatologists andresearchers in rheumatology,It is a real pleasure to be sharingwith you the “best of” the lastACR congress, prepared byEMEUNET members.EMEUNET continues to grow asa group of young Europeanrheumatologists and researchers,aimed at promoting educationand research, wideningcollaborations and integratingwith EULAR activities.New and exciting projects arecoming, namely a dedicatedEMEUNET website and aEULAR epidemiology course co­organized by EMEUNET in 2012.We want to keep you updatedwith our activities and will,therefore, start preparing moreregular newsletters (next issue tocome out during the firsttrimester of 2012). We hopeEMEUNET keeps beingembraced by the youngRheumatology community andmore of you become involved inrheumatology education,research and EULAR. Do nothesitate to sign up!We hope you enjoy reading thenewsletter,Best wishes,Sofia Ramiro & Pedro Machado(Portugal), newsletter editors

ACR 2011 Highlights!

emeuneWSemeunetTHE EMERGING EULAR NETWORK

THE NEWSLETTER OF

Hans Ulrich Scherer(The Netherlands)

BASIC RESEARCH II (Sofia Ramiro & Pedro Machado)

Sofia Ramiro, MD MSc, is aRheumatology fellow at HospitalGarcia de Orta (Portugal) andcurrently a PhD candidate (researchfocus on spondyloarthritis) at theAcademic Medical Center/Universityof Amsterdam (Prof. R. Landewé andProf. D. van der Heijde). Master’s inEpidemiology at MaastrichtUniversity.Pedro Machado, MD MSc, is arheumatology fellow at CoimbraUniversity Hospital (Portugal),currently doing research inspondyloarthritis as a doctoral fellowat the Department of Rheumatology,Leiden University Medical Center(Prof. D. van der Heijde and Prof. R.Landewé).

BASIC RESEARCH I (Caroline Ospelt & Mojca Frank)Sofia Ramiro, MD MSc, is a Rheumatology fellow at HospitalGarcia de Orta (Portugal) and currently a PhD candidate(research focus on spondyloarthritis) at the Academic MedicalCenter/University of Amsterdam (Prof. Landewé and Prof. vander Heijde). Master’s in Epidemiology at Maastricht University.

Caroline Ospelt started her medical studies at the Leopold­Franzens University of Innsbruck, Austria in 1995 andfinished in 2003 with her doctorate thesis. Since 2003 sheworks as a post­doctoral fellow in the Center of ExperimentalRheumatology, Zurich, Switzerland.

De Hair et al. (AB 770) from the Amsterdam Medical Center inthe Netherlands histologically analyzed synovial tissues fromseropositive, pre­clinical RA patients with arthralgia. At this timepoint of RA no signs of joint inflammation such as increasedlevels of macrophages or lymphocytes were found. Additionally,possible mediators of joint pain such as PGES­1, COX1/2 or 15­PGDA were found at normal levels in these patients. This studysuggests that serological changes seen in RA precede activejoint inflammation in RA patients.Pandis I. and co­workers (AB 832) from the Biomedical SciencesResearch Center Alexander Fleming, Vari, Greece have exploitedthe predictive value of the human TNF transgenic (TghuTNF,Tg197) mouse model in identifying novel microRNAs associatedwith RA pathogenesis. TghuTNF synovial fibroblasts exhibited asignificantly distinct microRNA expression profile with 12upregulated and 16 downregulated microRNAs, compared to wildtype synovial fibroblasts. The comparative analysis of theTghuTNF microRNA profile with human patient data identifiedthree novel microRNAs (miR­221, miR­222 and miR­323­3p) tobe associated with human RA. These microRNAs wereupregulated in TghuTNF vs. wild type and RA vs. OA synovialfibroblasts and were shown to act in part via direct targeting ofnegative regulators of Wnt/Cadherin pathways involved in RApathogenesis.Monica Guma and co­workers (AB 833) from the UCSD Schoolof Medicine, La Jolla, CA presented their work showing apossible explanation for the failure of p38α inhibitors in clinicaltrials. By using the K/BxN arthritis model in p38α ­/­ mice theycould show a worsened disease based on an increase in theproduction of proinflammatory pathways in macrophages.Furthermore, while in p38α inhibitor­treated macrophages IL­10levels decreased after LPS stimulation in vitro, IL­10 levels werenot affected in NKK3 ­/­ mice and NKK6 ­/­ macrophages.Accordingly, K/BxN arthritis was ameliorated in NKK3 ­/­ mice,suggesting NKK3 as a preferable therapeutic target.Connolly et al. (AB 1672) from the Center of ExperimentalRheumatology, Zurich, Switzerland presented microRNA­323 asa novel microRNA possibly involved in the pathogenesis of RA.This microRNA was significantly upregulated in RA synovialfibroblasts compared to OA. Furthermore, overexpression ofmicroRNA­323 resulted in significant increases in MMP­1,­3 andIL­8 and enhanced migration and proliferation of RA synovialfibroblasts. Finally they demonstrated that MMP­2 is activated bymiR­323 while TIMP­3 is a direct target of microRNA­323. Thismay provide a potential mechanism for invasion of RA synovialfibroblasts into cartilage.

Mojca Frank, MD PhD, graduated at the Faculty of Medicine,University of Ljubljana (2005) and gained her PhD inBiomedicine, University of Ljubljana in 2010. Since 2011 sheworks as a postdoctoral research fellow in the Center forExperimental Rheumatology, Zurich, Switzerland.

Bonelli et al. (AB 817) aimed at further elucidating the mechanismof CTLA­4Ig and, therefore, performed phenotypic and functionalanalysis of antigen presenting cells in rheumatoid arthritis patientsbefore and after the initiation of CTLA­4Ig therapy (abatacept). Theauthors showed that CTLA­4Ig directly affects phenotypic andfunctional characteristics of monocytes, which might decreasemonocyte migration to the synovium. These findings represent anadditional mechanism of CTLA­4Ig therapy in RA.A study on the regulatory effect of B cells on the type I interferonresponse by plasmocytoid dentritic cells (PDC) by Rönnblom et a.l(AB 2496) identified an important interaction between the inate andadaptative immune system. B cells seemed to promote the PDCfunction and to increase the type I IFN response to several differentIFN­α inducers. B cells enhanced the IFN­α production by PDCboth via cell­cell contact and soluble factors depending on stimuli.This PDC­B­cell cross­talk may play a role in the ethiopathogenesisof SLE.Su et al. (AB 851) presented a study on the identification andcharacterization of fibrinogen­specific CD4+ T cells and found thatT cells that recognize citrullinated fibrinogen can be detected in theperipheral blood of healthy individuals. These specific populationscontain large numbers of antigen­experienced T cells, many ofwhich exhibit a Treg phenotype. The authors hypothesize that adeficiency in citrullinated fibrinogen specific Tregs may contribute toexaggerated effector activity against citrullinated fibrinogen in RApatients.In patients with ACPA positive RA, Scher et al. (AB 2518) showedthat new­onset, never­treated RA patients had a distinct oralmicrobiome (compared to chronic­established RA and healthyindividuals), characterized by the overabundance of a single andvirulent Porphyromonas species, suggesting that furtheridentification and characterization of this species may helpexplaining the reported link between RA and periodontal disease.In another interesting study, Quirke et al. (AB 2522) showed thatthe immune response to autocitrullinated Porphyromonas gingivalispeptidylarginine deiminase (PPAD) was significantly elevated in RApatients compared to periodontitis patients and controls,suggesting that a heightened immune response to autocitrulilinatedPPAD is a potential mechanism for breaching immunologictolerance in RA. Laplante et al. (AB 724) studied the interactiveeffects of anti­phospholipid antibodies (aPL) and toll­like receptor(TLR) ligand by two complementary approaches: in vitroendothelial cell studies and an in vivo model of thrombosis; thisstudy suggested that aPL and TLR4 activation interact to promotethrombogenesis, which may explain why only certain individualswith aPL develop thrombotic events.

In this edition of EMEUNEWS we would like to draw your attention towhat we believe were the most interesting presentations at this year's ACR

EDITORIAL

Original layout

Pedro Machado, MD MSc, is a rheumatology fellow at CoimbraUniversity Hospital (Portugal), currently doing research inspondyloarthritis as a doctoral fellow at the Department ofRheumatology, Leiden University Medical Center (Prof. D. vander Heijde and Prof. R. Landewé).

02 NOVEMBER 2011 EMEUNEWSRHEUMATOID ARTHRITIS I (Cécile Gaujoux­Viala) RHEUMATOID ARTHRITIS II (Jackie Nam)

Cécile Gaujoux­Viala, MD PhD fellow in the graduate school BioSE, occupies a half­time clinical and half­time research and teaching position at the Paris 6 Universityand Pitié­Salpêtrière Hospital in Paris. Her major research interest is outcomeassessment, in particular evaluation of the benefits in health in bone and jointdiseases, especially in rheumatoid arthritis.

Jackie Nam is a rheumatology clinical research fellow in Leeds, UK. Areas ofinterest include the diagnosis and management of early arthritis.

Cardio­vascular risk in RA :RA is associated with an increased cardiovascular risk, but mechanisms explainingthis increased risk have not been fully elucidated. Several hypotheses have beensuggested:

­ Vulnerable coronary plaques, in particular high risk mixed plaques (Karpouzas etal., AB 759)

­ Outward remodelling (van Sijl et al., AB 760)­ Abnormal concentric left ventricular remodelling (Davis III et al., AB 761)­ Disturbance of lipid metabolism

The results of 2 small studies suggest a potential mechanism by which activeinflammation from RA increases oxidized fatty acids in circulating lipoproteins,promoting LDL oxidation and HDL dysfunction, thereby increasing atherosclerotic risk(Charles­Schoeman et al., AB 763 & AB 764).In an inception RA cohort, the use of MTX or TNF­α inhibitors was independentlyassociated with a 46% reduction in incident cardio­vascular events compared to non­users (Bozaite­Gluosniene et al., AB 719).Pathophysiology of RA:P. gingivalis (Pg) leading to periodontal disease (PD) has emerged as a potentialenvironmental risk factor in RA. Immunity to Pg is significantly associated with thepresence of RA­related autoantibodies in first­degree relatives of RA probands,including those at highest risk for future RA. This association is independent of otherfactors associated with both RA and PD risk. These results support the hypothesisthat infection with Pg may play a central role in the early loss of tolerance to selfantigens and may explain prior reported associations of periodontitis with risk forestablished RA (Mikuls et al., AB 766).Airways abnormalities on high­resolution computed tomography are present in a highproportion of RA­specific autoantibodies+ cases without inflammatory arthritis, andthese lung abnormalities are similar to those in patients diagnosed with early RA(Demoruelle et al., AB 769). This suggests that there is a continuum of lung injuryduring the development of RA, and that lungs are either a site of RA­relatedautoimmune­mediated injury during the pre­symptomatic phase of disease, or morelikely a site of initiation of RA­related autoimmunity perhaps due to external factors(smoking…).Furthermore another study demonstrated that long­term exposures to ambient airpollution particularly SO2, were associated with risk of RA in 2 cohorts (Hart et al., AB2574).RA treatments:The TEAR trial, in early poor prognosis RA, randomized 755 patients to initial MTXversus immediate combination therapy (MTX/ etanercept orMTX/Sulfassalazine/Hydroxychloroquine). MTX only patients stepped­up tocombinations at 24 weeks if they failed to achieve low disease activity. The resultshave for the first time validated the recommended strategy of starting with MTXmono­therapy. If this is done, approximately 30% of patients will not needcombination therapy and the 70% who need add­on therapy will be clinicallyindistinguishable from those that received immediate combination therapy 3 monthsafter step­up and importantly radiographically indistinguishable at 2 year (O’Dell etal., AB 1696).

Anti­TNFMecer et al. (AB 2525) reported 5 year data from the British Society forRheumatology Biologics Register ­ no signal of increase risk of solid cancer wasseen in patients receiving anti­TNF therapy for RA (hazard ratio (HR) 0.88 (0.65,1.17)) compared to a group receiving DMARD therapy alone. The adjusted HR foretanercept was 0.94 (0.68, 1.29), infliximab 0.87 (0.61, 1.25) and adalimumab 0.81(0.57, 1.14). There was no significant difference in risk of colorectal, lung/ bronchusor female breast cancer. Anti­TNF therapy has been associated with increased riskof serious infections. Curtis et al. (AB 462) evaluated the association between anti­TNF therapy and serious infection in 7537 RA patients initiating infliximab (n=3036),etanercept (n=2253) and adalimumab (n=2248) to determine whether this risk wasincreased for patients of older age or comorbidities. The overall observed 1­yearrisk of infection was 15.3, 13.1, and 13.7 per 100 person years respectively. Ageand other comorbidities were not found to not confer an additional risk of infection.B­cell therapyKeystone et al. (AB 2208) reported the long­term radiographic efficacy of rituximab(RTX) in TNF­IR RA patients. Five­year analysis of the REFLEX study, showedinhibition of joint damage in patients originally randomized to (1) RTX and (2)placebo (PBO) + later rescue with RTX with the RTX group demonstrating greaterinhibition of joint damage at 5 years compared with patients originally randomized toPBO. Dougados et al. (AB 452) assessed the clinical efficacy and safety of 2 doseregimens of RTX (Arm A 1g single infusion vs. Arm B 2x1g) in patients who had aEULAR response (good or moderate) 6 months after a 1st cycle of RTX 2x1g andwho needed subsequent therapy. The DAS28­CRP AUC at week 104 (per­protocolpopulation) was 2761±508 in Arm A and 2666±490 in Arm B, adjusted inter­groupdifference of 51.4, [95% CI ­131.2; 233.9]. The non­inferiority of retreatment in ArmA vs. Arm B demonstrated, suggests that after initial response to RTX, treatmentwith a RTX 1g single infusion may provide similar clinical outcomes compared with2x1g infusions. Radiographic outcomes still need evaluation. Vital et al. (AB 1643)investigated predictors of sustained response to RTX at 12 months. In patients withdetectable B cells at 6 months, DAS28 worsened by mean (SD) 0.45 (1.06),whereas patients with undetectable B cells DAS28 improved by mean 0.44 (0.45)(p< 0.001). A combination of B cell repopulation and serum rheumatoid factor werefound to be useful to predict relapse after initial response at 6 months.

The topic of new drugs beyond byologics was introduced by Prof. Iain B. McInnes(University of Glasgow, United Kingdom) in an immunology update for clinicians onSyk, Jaks and Btk: new targets in rheumatoid arthritis. Throughout the meetingmany posters and presentations described either safety data, tolerability, clinical ef­fects and radiological effects of tofacitinib (CP­690,550), an oral jak (janus kinase)­inhibitor. Treatment with tofacitinib at doses of 5 or 10 mg BID in patients with RAdemonstrated a well­tolerated safety profile (although infections and gastrointestinalcomplaints occurred more frequently in the tofacininib group) and sustained long­term efficacy over a 36­month period (ACR 20 72.7%, ACR50 52.3%, and ACR7035.2%). Combination with methotrexate significantly reduced the progression ofstructural damage compared to placebo in patients with active RA on methotrexate(AB 407 & 2592). Other potential new small molecule therapeutic compounds inclu­ded the oral S1P lyase inhibitor LX3305 that exhibited a favorable safety profile anda potential clinical benefit in patients with active RA despite stable­dose MTX the­rapy supporting further clinical development of LX3305 as a small molecule therapyfor RA (AB 2593). Furthermore, the effects of several new oral spleen tyrosine kina­se (syk) inhibitors have been presented (AB 437 & 2084). Also, promising pre­clini­cal data on Bruton’s tyrosine kinase (btk) inhibition were presented (AB 1757 &1758). Another interesting therapeutic target is TNF­like weak inducer of apoptosis(TWEAK). Both TWEAK and its sole signaling receptor FGF­inducible molecule 14(Fn14) are highly upregulated locally in the end organ targets of inflammatory andautoimmune diseases. Single dose administration of BIIB023 (Anti­TWEAK)showed a favourable safety and tolerability profile in subjects with RA and suppres­sed serum soluble TWEAK, a biomarker of target engagement, for up to 4 weeks.The pharmacokinetic profile of BIIB023 supports further development in inflamma­tory and autoimmune diseases (AB 2201). The effects of new drugs for earlier iden­tified targets have also been presented in this year’s meeting such as sirukumab, ahuman anti­IL­6 monoclonal antibody, for RA (AB 2632) and secukinumab, an anti­interleukin 17A monoclonal antibody, for psoriatic arthritis (AB 779), that both redu­ced signs and symptoms in multicenter, international, double­blind, randomized,placebo­controlled trials.

RHEUMATOID ARTHRITIS III (Sander Tas)Sander W. Tas, MD PhD, is an Internist­Rheumatologist at the Academic MedicalCenter (AMC)/University of Amsterdam. His research interests are rheumatoidarthritis, NF­kappaB signaling, dendritic cells, angiogenesis and gene therapy.

EMEUNET is co­organizing an EULAR­endorsed Epidemiology course.What: Epidemiology courseWhen: 6­7 July 2012 (1.5 days)Where: Berlin, Germany (German Rheumatism Research Center)Details: course targetting young researchers with an interest inepidemiology. The course will focus on the design, analysis andinterpreration of observational studies.Faculty: Daniel Aletaha, Loreto Carmona, William Dixon, Robert Landewé,Désirée van der Heijde, Angela ZinkCourse organizers: Daniel Aletaha, Loreto Carmona, Laure Gossec,Pedro Machado, Angela ZinkSave the dates. More information soon!

EULAR EPIDEMIOLOGY COURSE 2012

EMEUNEWSAXIAL SPONDYLOARTHRITIS (Isabel Castrejón)

SYSTEMIC LUPUS ERYTHEMATOSUS &ANTIPHOSPHOLIPID SYNDROME (Neil Basu)

Laure Gossec, the current lead of EMEUNET, is associate professor of rheumatologyin Cochin Hospital, Paris, France but is currently working in the ManchesterEpidemiology Unit (UK). Her main interests are outcomes research and patient­reported outcomes, in particular in rheumatoid arthritis and psoriatic arthritis.

Isabel Castrejon, MD, is a clinical research fellow working in a research programconcerning outcomes in rheumatic diseases in the Division of Rheumatology, Hos­pital for Joint Diseases, NY, under the supervision of Professor Theodore Pincus.She was trained in Rheumatology at the Hospital Universitario de La Princesa, Ma­drid (2007).

Neil Basu is a consultant rheumatologist currently completing a PhD inepidemiology at the University of Aberdeen, Scotland. His main research interestslie in the field of vasculitis and the investigation of rheumatic fatigue.

Predictors of PsA onsetWe know that in most cases, psoriasis precedes PsA – but which psoriasis patientswill develop PsA? Ogdie et al. (AB 782) reported that the extent of psoriasis washighly predictive of PsA. This was based on a survey of 4634 English patients withpsoriasis, of whom 1.9% developed PsA. In the same cohort, but using anothermethodology and a different definition of the cohort (in this case, 75,395 individualswith skin psoriasis, 976 of whom developed PsA), Zhu et al. (AB 2533) indicated thatbody mass index at diagnosis of psoriasis was predictive of the onset of PsA. Here isa first argument suggesting the usefulness of weight control in patients withpsoriasis. And weight control should be maintained in patients with PsA, given theirincreased cardiovascular risk (AB 500, 534, 547, 1332, 1868, 1871 & 2634).Some presented data were consistent with the Leeds hypothesis of a complexincorporating nail, enthesis, joint and bone in PsA. Tan et al. (AB 1702) presented anoriginal study by PET of the hands of 30 PsA subjects, which suggests that there isan increased bone metabolism in the fingers of PsA patients, particularly in theentheses around the nail matrix. The same Leeds team (Ash et al., AB 2486F)indicated ultrasonographic inflammation of the entheses, in psoriasis patients withjoint pain but without visible joint inflammation, in particular in cases of nailinvolvement.Prognostic factors in PsAWhat elements predict radiographic severity? At this congress, the role of synovitis(AB 1288 and 504) and of elevated acute phase reactants (AB 1288 and 1548) wasput forward. Gender may also play a role in severity. Eder et al. (AB 2486c) indicatedthat visible joint destruction and radiological joint destruction were more important formen, in the Canadian cohort of 635 PsA. The odds ratio was around 1.5. In addition,axial involvement was more common in men (odds ratio 2.1).‘Window of opportunity’ in PsA?Kavanaugh et al. (AB 1288) suggest there may be some added benefit to earlytreatment. This re­analysis of the PRESTA clinical trial indicates that patients treatedwithin the first 2 years of their disease showed greater clinical improvement withetanercept than those treated later. However, difference were only apparent for someof the clinical criteria, and importantly, radiographic progression was not addressed.

Two interesting abstracts highlighted the risk of cigarette smoking in the level ofinflammation and radiographic damage in patients with Axial Spondyloarthritis(SpA): Poddubnyy et al. (AB 777) and Machado et al. (AB 1650). In the first studyauthors concluded that smoking is associated with higher spinal radiographicprogression and in the second study authors confirm an association of smokingwith earlier onset of symptoms, higher disease activity, poorer functional status andaxial structural damage on MRI and radiographs. Another study by Yoon et al. (AB512), designed to determine predictors of radiographic severity of sacroileitis, foundthat smoking is the only modifiable risk factor for the development of severeradiographic damage (OR 1.13, 95% CI: 1.04­1.23), although other not modifiablerisk factors have higher OR as family history (OR 4.65, 95% CI: 1.44­15) and non­Caucasian ethnicity (3.3, 95% CI: 1.26­8.79).In a study based on the German Spondyloarthritis Cohort, Poddubnyy et al. (AB2486B) describe that a high NSAIDs intake over two years, defined by an indexrecommended by ASAS, is associated with a significantly lower rate of radiographicprogression. It was presented an exploratory study (n=30) by X. Baraliakos et al.(AB 2486D), on the efficacy of secukinumab, an inhibitor of IL­17A, suggesting areduction of spinal inflammation detected by MRI 6 weeks after start of treatment.Another interesting study about therapy by Nissen et al. (AB 2637) show that co­therapy of DMARDs on anti­TNF is prescribed by a 31% of physicians in patientswith SpA (axial SpA, psoriatic arthritis or undifferentiated arthritis) from the Swissregistry. Interestingly, co­therapy patients are older and less likely to be HLA­B27positive or to exhibit pure axial manifestations. No benefit of DMARDs co­therapyon anti­TNF was demonstrated (hazard ratio 1.06, 95% CI: 0.90­1.24) supportingcurrent recommendations.Three abstract address the impact of gender in severity and clinical presentation ofSpA using different strategies. Patel et al. (AB 505) explore the correlation betweenBASFI and AS­metrology showing a stronger correlation in men compared towomen. Paramarta et al. (AB 521) showed that psoriatic arthritis is significantlymore common in men (32% vs 18%) and BASDAI (5.3 vs 4.3) and ESR (14 vs 7)were significantly higher in women. Lastly, F. Pimentel­Santos et al (AB 1317) showthat BASDAI is higher in women (4.9 vs 3.7) as well as BASFI (4.5 vs 3.8) butopposed to BASMI that is higher in men (4.3 vs 3.5).

A number of ‘hot topic’ areas were advanced. As reported by observational studieselsewhere, the South American GLADEL cohort substantiated the protective effect ofanti­malarials in the development of cardiovascular disease in SLE (AB 783).Intriguingly and in contrast with previous data, the Johns Hopkins group identifiedmethotrexate to be associated with the development of non­calcified coronaryplaques, as measured by CTA. The authors stressed the exploratory nature of theseresults and the need for further investigation before questioning the role of thiscommonly used lupus agent (AB 784).Cohort studies reported some reassuring data regarding pregnancy outcomes. Alarge multi centre European study followed the outcomes of children born to 140 APSmothers and revealed no concerning developmental abnormalities or complications(e.g. SLE, thrombosis) after 5 years follow up (AB 728). Fischer­Betz and colleaguesexamination of 21 pregnant APS with a history of previous cerebral ischemia foundhigh rates of pre­eclampsia and premature birth but low risk of recurrent cerebralevents in the mother (6). The PROMISSE analysed 333 APS and SLE pregnanciesfor predictors of poor outcome. Patients with stable disease at conception did well,the main adverse predictors being gestational disease flares and high baseline urateand ApL levels (AB 1707).No ground breaking intervention studies were presented. Post­hoc analysis ofpreviously reported biological trials was popular. A phase III abatacept lupus nephritistrial failed to show overall superiority in primary endpoints compared to placebo, butfurther analysis suggested clinically significant benefit in a subset of nephritic disease(AB 2649). Pooled analysis of 2 recent belimumab RCTs also indicated benefit insome patients with lupus nephritis (AB 2472). Omega 3 fatty acids did not benefitlupus disease activity in a 12 week RCT. While Bello and colleagues suggests longertreatment and follow up may be required, an observed increase in cholesterol maydeter future investigators (2471). Finally, examination of a substantial SLE cohortrevealed no clinical benefit from vitamin D supplementation. While a RCT mayaddress the impact of vitamin D more definitively, the author’s still encouragesupplementation in those at risk of poor bone health (AB 786).

EULAR 2012 abstract submission is open and the deadline is January31st. We hope that young rheumatologists and researchers can have anotable presence in the conference currently recognized as the primaryplatform for rheumatology education and information exchange. Submityour abstracts!EULAR AwardsEULAR offers three types of Awards for the EULAR 2012 Congress:EULAR Abstract AwardEULAR bestows awards to the first authors of the 6 highest scoredabstracts in Basic Science topics and of the 6 highest scored abstracts inClinical topics.EULAR Abstract Award for Undergraduates/StudentsThis award will be given to the highest scored abstract submitted by anUndergraduate/Student as the first author.Health Professional Abstract AwardThis award will be given to the highest scored abstract submitted in theHealth Professionals in Rheumatology category by a Health Professional.All awards consist of a free registration to the EULAR 2012 Congress andEUR 1000 prize money awarded to the first author of the abstract.

NOVEMBER 201103PSORIATIC ARTHRITIS (Laure Gossec)

EULAR ABSTRACT SUBMISSION AND AWARDS!

04 NOVEMBER 2011 EMEUNEWSOTHER CONNECTIVE TISSUE DISEASES & VASCULITIS(Gulen Hatemi)

OSTEOARTHRITIS & FIBROMYALGIA (Ladislav Senolt)Ladislav Senolt is a consultant rheumatologist, senior lecturer (Assoc. Prof.)and head of connective tissue research laboratory, Institute of Rheumatologyin Prague, Czech Republic.

Gulen Hatemi, MD is a rheumatologist in Istanbul University, Cerrahpasa MedicalSchool, Department of Internal Medicine, Division of Rheumatology. Her main areasof research interest are Behçet’s syndrome, familial Mediterranean fever andvasculitis.

IMAGING (Espen A. Haavardsholm)

Espen A. Haavardsholm, MD PhD, is leader for the clinical research section of theoutpatient clinic at the Dept. of Rheumatology, Diakonhjemmet Hospital, Norway.Main research interests: Imaging in inflammatory rheumatic diseases ­ especiallyMRI and US.

Stone et al. (AB 2432) reported the long term follow­up of ANCA associated vasculitis(AAV) patients who had been included in the RAVE trial comparing rituximab andcyclophosphamide. Rituximab (375 mg/m2 x 4) was as effective ascyclophosphamide followed by azathioprine for maintenance at the end of 18months, regarding complete remission rates and the number and severity of flares.However, whether there was a difference between the 2 treatment arms amongthose who had used cyclophosphamide before the RAVE trial and had entered thetrial with a relapse was not clear. Another study by the same group showed that theproportion of patients in the RAVE trial with low immunoglobulin levels increasedsimilarly in both treatment arms at month 6 and month 18, but the lowimmunoglobulin concentrations were not associated with an increased rate ofinfections (AB 789). Pagnoux et al. (AB 2368) analyzed the data of 423 patients withAAV who had entered observational cohorts and 220 such patients who had enteredtherapeutic clinical trials to determine whether patients included in clinical trials arerepresentative of patients routinely seen in vasculitis clinics. Patients included inclinical trials had significantly more lung, cardiovascular, gastrointestinal and renalinvolvement, higher disease activity at baseline and higher mortality rates,suggesting that caution is required when interpreting the results of clinical trials inAAV.A prospective observational study to examine the effects of mycophenolate mofetil(MMF) on skin and pulmonary involvement in 25 patients with recent onset systemicsclerosis (SSc) showed that modified Rodnan skin score and affected body surfacearea improved significantly over a mean of 18 ± 9 months, fibrotic tissueaccumulation was reduced and TLC and DLCO levels remained stable (AB848). Aplacebo­controlled RCT with trepostinil diethanolamine in SSc patients with digitalulcers failed to show an improvement in net ulcer burden at week 20 (AB 2483).Gordon et al. (AB 1716) evaluated SSc patients with pulmonary arterial hypertensionand pulmonary venous hypertension in the PHAROS database and showed thatpatients in the second group were more likely to be African American, male andyoung, to have diffuse cutaneous SSc and to be anti­Scl70 antibody positive. Thedifferences in prognosis of the 2 groups remains to be seen. Johnson et al. (AB2481) reviewed the charts of SSc­associated and idiopathic PAH patients to evaluatethe effect of warfarin on improving survival and concluded that this was probably notthe case in either group (HR 1.06 and 1.07 respectively). More information on SScresearch at ACR can be found on the young investigators’ page at www.eustar.org.

In a sub­analysis of the OPTIMA trial in 70 patients with MRIs of the mostclinically severe hand, Peterfy et al. (AB 1612) showed that treatment withadalimumab and methotrexate (MTX) resulted in greater reductions insynovitis, osteitis, and bone erosion MRI scores compared withplacebo (PBO) and MTX at 26 weeks in patients with early RA. The authorsconclude that the strong correlation between change in osteitis and changein erosion corroborates the current view that osteitis is a precursor oferosion. Smolen et al. (AB 1614) presented data evaluating if IL­6inhibition with tocilizumab (TCZ) interferes with joint destruction beyondits effects on disease activity (DA) in RA patients. In this analysis theyshowed that progression of the Genant modified total Sharp score (TGSS)was similar between treatment groups when remission or low DA was reached,and that in contrast, when only moderate or high DA was reached after1year, placebo treated patients had significantly higher TGSS change thanthose treated with TCZ. Thus, IL­6 receptor inhibition appears to inhibitjoint damage progression independent of its impact on disease activity.Bongartz et al. (AB 1617) assessed the accuracy of dual energy CT scanning(DECT) to detect monosodium urate (MSU) deposits to diagnose gout, andfound a sensitivity and specificity of DECT of 0.93 and 0.95,respectively, concluding that DECT is a high­yield test with significantimpact on clinical decision making when gout is suspected, but polarizingmicroscopy of synovial fluid fails to demonstrate MSU crystals. O’Dell etal. (AB 1696) reported data from the investigator initiated TEAR trial,examining the strategy of using MTX monotherapy as the first interventionin RA. They showed that the MTX group had less radiographic progressioncompared to immediate combination therapy. These data have for the firsttime validated the recommended strategy of starting with MTX monotherapy,showing that approximately 30% of patients will not need combinationtherapy and the 70% who need add­on therapy will be clinicallyindistinguishable from those that received immediate combination therapy 3months after step­up, and radiographically indistinguishable at 2 years.Van der Heijde et al. (AB 2592) reported data from a 24 month phase 3double­blind RCT of tofacitinib in combination with MTX in 797 patientswith active RA with inadequate response to MTX, evaluating the efficacy,including reduction of structural damage progression of tofacitinib vsplacebo, showing that tofacitinib significantly reduced progression ofstructural damage vs PBO.

Several papers studied obesity­related factors and anti­aging proteins inosteoarthritis (OA). De Boer et al. (AB 1080) showed that circulating adipokines areincreased in patients with end­stage knee OA. Koskinen et al. (AB 1776)demonstrated that adiponectin correlates with OA biomarkers, radiographic severityof OA as well as with production of catabolic and inflammatory factors produced bycartilage. Furthermore, Junker et al. (AB 1825) found visfatin, resistin andadiponectin as potential factors involved in osteophyte formation. Histonedeacetylase Sirt 1, an anti­aging protein, has been demonstrated to play a protectiverole in cartilage homeostasis. Gabay Engel et al. (AB 1795) showed that Sirt1 knock­out mice exhibit low levels of extracellular matrix proteins, high levels of matrixdegrading enzymes and apoptotic features leading to an increase of cartilagebreakdown.In a prospective, multinational, observational cohort study, Daniel Prieto­Alhambra etal. (AB 829) demonstrated on 51,386 postmenopausal women that patients reportingOA have a 20% higher risk of fracture and experience almost 30% more falls thanthose without OA. They suggested that fall prevention strategies may form part of thewhole person management of OA patients. Yusuf Yaziciet al. (AB 828) presentedresults from a phase III study evaluating efficacy and safety of intravenoustanezumab, a monoclonal antibody that inhibits nerve growth factor, in patients withmoderate to severe knee or hip OA. The authors concluded that tanezumabmonotherapy resulted in superior analgesic efficacy and improvements in pain andfunction compared with naproxen and celecoxib. However, an increased risk ofrapidly progressive OA, particularly for tanezumab combined with NSAIDs wasnoted. Interesting study performed by Wiegant et al. (AB 827) showed that knee jointdistraction resulted in significant clinical benefit accompanied by cartilage repair inend­stage knee OA.

Wolfe et al. (AB 1610) assessed drug use and outcome variables on 2,870 patientswith fibromyalgia. Opioid use remained high in fibromyalgia and switching frominexpensive generic trycyclics to newer and expensive serotonin­norepinephrinereuptake inhibitors and anticonvulsant agents was common. Although, drug costsincreased substantially (from $459 to $1,345), no clinically significant changes inpain, fatigue and function were noted during 11 years of follow­up. Interestingly,Ogino et al. (AB 1606) investigated 5­hydroxytryptamine (5­HT2) C receptoragonists in animal models of fibromyalgia and found that 5­HT2C receptors play acritical role in pain transmission in the reserpine­induced muscle hyperalgesia. Theysuggest the therapeutic potential of 5­HT2C receptor agonists in treatingfibromyalgia.

EMEUNET is preparing a new website. The working group membershave designed the website and are now at the stage of gathering thecontents, before an IT company can proceed with its development.Usefulness of the website for young rheumatologists and researchershas been the central issue. We want to create a website which youngrheumatologists and clinicians want to visit due to gathering usefulinformation that usually can only be found in several different sources.The website will have many important links ­ information about courses,grants, fellowships, clinical links by disease, among others and will alsoserve as a platform to find the contacts of other young rheumatologistsand researchers across Europe.It is expected to be launched before EULAR 2012 and we will give moreupdates on its progress.

EMEUNET WEBSITE

emeunetTHE EMERGING EULAR NETWORK

METABOLIC & CRYSTAL ARTHROPATHIES (Francisca Sivera) OSTEOPOROSIS & METABOLIC BONE DISEASE(Peter Mandl)Francisca Sivera is a rheumatologist in Hospital de Elda, Alicante (Spain) and has

a well known interest in crystal arthritis having published several papers and hasrecently been involved in the development of the EULAR recommendations on thediagnosis and management of CPPD.

Peter Mandl is a Consultant Rheumatologist, currently doing research inosteoimmunology and musculoskeletal ultrasonography as a Post­Doctoral Fellowat the Division of Rheumatology, Medical University of Vienna. Peter will serve asChairperson of EMEUNET in 2012.

This year the ACR was full of abstracts and posters on crystal arthritis, especiallygout. Data keep on accumulating on the effects of IL­1 blocking therapies on gout­related inflammation. The short­term safety of Rilonacept in patients initiating orcontinuing on urate­lowering therapy has been shown in an analysis integrating fourplacebo­controlled RCTs; the overall rate of serious infections was low and the mostcommon adverse event leading to discontinuation was injection site reactions(Terkeltaub et al. AB1015). Of note, no clear warning signal on infections emerged.After the FDA voiced concerns regarding Canakinumab, long­term data of repeateddoses will probably be forthcoming.Given current concerns over the costs of these (and other) new therapies, severalabstracts address the costs related to gout (Chenghui et al., AB 896). Resourceutilization and costs have been linked to frequency of gout flares, comorbidities andserum urate levels (Rascati et al., AB 889; Saseen et al., AB 893; Navaratnam et al.,AB 897).For allopurinol therapy, allopurinol­associated hypersensitivity syndrome (AHS)continues to be the most feared complication, as it is still unclear which patients aremore prone to develop it. A retrospective case­control study including 54 goutpatients who developed AHS and 157 controls shows an association between thestarting allopurinol dose and the risk of AHS but not for the maximum allopurinoldose (Stamp et al., AB 2579). This highlights the need to ‘start low, go slow’ inallopurinol dosing.Data also keeps accumulating regarding the link between gout and cardio­vascularevents. A systematic review of population­based observational studies showed thatgout was associated with an increased risk of incident acute myocardial infarction(RR 1.11­1.50). (Schieir et al., AB 114) Also, the relationship between renal outcomesand serum uric acid has been explored in a post­hoc analysis of patients enrolledinto the febuxostat trials, a decrease in serum uric acid levels correlated with reduceddeterioration of renal function, especially in patients with baseline filtration rates<60mL/min. (Whelton et al., AB 1031).

High HAQ, old age, history of total knee replacement, and low BMI wereassociated with incident hip fractures in a study conducted on 9,720 Japanese RApatients (Furuya et al., AB 1629). An incident vertebral fracture (VF) rate of 6%was shown in children with rheumatic diseases at 12 months following GCinitiation. Children with incident VF received more GC, had greater increases inBMI and greater declines in spine BMD Z­scores in the first 6 months of GCtreatment (Lang BI et al. 1633). The Lancaster Osteoporosis Predictor, a novel toolto identify individuals with osteoporosis (OP), developed on a very large UK cohortwas shown to reduce the number of DEXA scans by 51% in females and 32% inmales; 8.6% of females and 16% of males not scanned will be osteoporotic(Oldroyd et al., AB 1105). A retrospective evaluation of 130 OP patients treated forthe first time with i.v. zoledronate confirmed the association between low serum25(OH) levels and the development of acute phase response (APR) and showedthat previous amino­bisphosphonate treatment could reduce APR incidence afterthe first infusion (Massarotti et al., AB 1120). In the FREEDOM trial denosumab(DMAb) showed significant increases at month 18 in both trabecular andperipheral volumetric densities for the spine, and a significant increase intrabecular density for the hip, as well as P1NP and CTX levels at months 3 and 6.Yearly incidences of serious adverse events of infection and adverse events ofmalignancy did not increase over 5 years of continuous DMAb treatment ofpostmenopausal women with OP. Imbalances regarding skin infections reported inthe original study were not observed in the extension study (Brown et al., AB 1098,1103) In a 4­year, phase 2 parent study on postmenopausal women continuousDMAb treatment for 8 years was associated with continued gains in BMD andpersistent reduction in bone turnover markers, and was well tolerated (McClung etal., AB 1107). Two p38 MAP­kinases MKK3 and MKK6 were identified as negativeregulators of bone homeostasis, as shown also by a pronounced increase in bonemass as well as partial protection against OVX­induced bone loss seen in MKK6­deficient mice (David et al., AB 1630). Bach1, a repressor of heme oxygenase­1was found to regulate osteoclastogenesis via both HO­1 dependent andindependent mechanisms, with Bach1 knockout mice being partially resistant toRANKL­dependent HO­1 reduction and showing impaired osteoclastogenesis(Hama et al., AB 1115).

EMEUNEWS NOVEMBER 201105

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