eular 2013 post digital · 11. treatment with tofacitinib can be considered after patients fail...

The eularReport

2013 An authorised publication of the

European League Against Rheumatism

Eular 2013 post digitalqxp 1042013 122 PM

2 14TH ANNUAL EUROPEAN CONGRESS OF RHEUMATOLOGY

Welcome to the EULARReport 2013

The Annual European Congress of Rheumatology hosted by the Eu-ropean League Against Rheumatism (EULAR) is recognized as the pri-mary platform for European rheumatology education and information

exchange in the world This yearrsquos EULAR Congress was no exception Over14000 attendees came to Madrid from 120 countries around the world (60from Europe) to hear the best in rheumatology research and clinical advancesThe scientific program contained presentations selected from 3889 abstractssubmitted

We hope that this report is of interest and value for those of you who wereunable to attend the EULAR Congress in Madrid and for those who did (sincenobody can expect to see all of the best of the Congress while there) TheEULAR Report brings you highlights of some of the best presentations fo-cusing on the sort of clinical and therapeutical findings that change the wayrheumatologists practice medicine

We hope that you will enjoy these accounts of the latest in rheumatologyclinical and translational research

Many of the research reports that you will find here also include accessto video interviews with the presenters

For details about the next EULAR Congress to be held 11-14 June 2014in Paris please visit wwweularorg

PROF MAXIME DOUGADOSPast President of EULARProfessor of Rheumatology at ReneacuteDescartes UniversityChief of the Department of Rheumatologyat Cochin Hospital Paris

The eular ReportAnalysis of Key Research Presented at the 14th Annual European Congress of Rheumatology

President IMNG Medical MediaAlan J ImhoffDirector IMNG Society PartnersMark BrancaEditorJeff EvansDesignerLisa MarforiProduction ManagerMaria Aquino

Copyright copy 2013 IMNG MedicalMedia All rights reserved Nopart of this publication may be reproduced or transmitted in anyform by any means without priorwritten permission of the Publisher IMNG Medical Mediawill not assume responsibility fordamages loss or claims of anykind arising from or related to theinformation contained in this publication including any claimsrelated to the products drugs orservices mentioned herein

Cover image Bernardo Diacuteaz

PROF MAURIZIO CUTOLOPresident of EULARProfessor of Rheumatology and InternalMedicineDirector of Research Laboratory andAcademic Unit of Clinical RheumatologyDepartment of Internal MedicineUniversity of Genova Italy

Eular 2013 post digitalqxp 1042013 123 PM Page 2



Revised EULAR Rheumatoid Arthritis Guidelines Keep Synthetic DMARDs First

B Y M I T C H E L L Z O L E R

In newly updated recommendationsfor managing rheumatoid arthritis aEULAR task force retained much

from its prior 2010 version but includedsome significant changes such as elevat-ing the biologic drugs tocilizumab andabatacept to the same status as tumornecrosis factor inhibitors

The 2013 draft revision may be mostnotable for what stayed the same from2010 such as keeping conventional syn-thetic disease-modifying antirheumaticdrugs (DMARDs) as the only first-lineinterventions for newly diagnosed pa-tients with rheumatoid arthritis (RA)This means the update keeps all biolog-ic DMARDs as secondary treatmentsreserved for patients who fail to respondadequately to or are intolerant ofmethotrexate or the other conventionalsynthetic DMARDs cited as first-lineoptions sulfasalazine hydrochloro-quine and leflunomide

By maintaining synthetic DMARDs ndasheither methotrexate monotherapy or incombined regimens ndash as its only first-line options for treating RA the Euro-pean League Against Rheumatism(EULAR) Task Force appointed to devel-op the new revision broke with the 2012RA management recommendations ofthe American College of Rheumatology(ACR) which cited treatment with a tu-mor necrosis factor (TNF) inhibitor as afirst-line option with or without com-bination with methotrexate for patientswith early RA high disease activity andpoor prognostic features (Arthritis CareRes 201264625-39)

The reason to keep all biologicDMARDs as second-line drugs was theevidence that supports the ldquoefficacy ofa treat-to-target strategy when addingbiologics after insufficient response tomethotrexaterdquo said Dr Josef S Smolenprofessor of rheumatology at the Med-ical University of Vienna who present-ed the draft update during a session atthe Congress Dr Smolen stressed thatalthough the EULAR-appointed 33-member update task force had complet-ed all their votes to approve the draft

recommendations the update was stillsubject to further review and change be-fore its eventual publication (See box toread all 14 recommendations)

The new draft ldquodoes not advocate useof biologics as first DMARD strategiesbecause the treat-to-target approach willlead to a similar overall outcome whileavoiding the overtreatment of 20-50of patients with early RArdquo Dr Smolen

explained The revision also does not en-dorse monotherapy with a TNF in-hibitor or any other type of biologicDMARD

Another major break from the past inthe new revision is its leveling of the rolefor tocilizumab and abatacept alongsidethe several TNF inhibitor DMARDs nowon the worldwide market Last yearrsquos

Continued on following page

The draft 2013 EULAR rheumatoidarthritis management recommenda-tions include three overarching princi-ples and 14 recommendations Here isa summary of the draft recommenda-tions

1 Therapy with DMARDs shouldstart as soon as rheumatoid arthritis isdiagnosed2 Treatment should aim to achieve re-mission or low disease activity3 Monitoring should be frequent andif there is no improvement after amaximum of 3 months or if the tar-get has not been reached by a maxi-mum of 6 months treatment shouldbe adjusted4 Methotrexate should be part of thefirst treatment strategy5 When methotrexate is contraindi-cated or not tolerated consider sul-fasalazine or leflunomide as part ofthe treatment regimen6 Early treatment with a combinationof conventional synthetic DMARDs isa reasonable alternative to initialmethotrexate monotherapy7 Consider adding a low-dose gluco-corticoid as part of initial treatmentfor up to 6 months taper down as rap-idly as clinically feasible 8 If the treatment target is notreached consider changing to anoth-er synthetic DMARD regimen if thepatient has poor prognostic featuresconsider adding a biological DMARD

9 If a patient does not respond ade-quately to treatment with convention-al synthetic DMARDs ndash with or with-out concurrent treatment with a glu-cocorticoid ndash a biological DMARDshould be started along with metho-trexate The biological DMARD couldbe a TNF inhibitor abatacept ortocilizumab10 Patients who fail to adequately re-spond to a biological DMARD shouldbe switched to another biologicalDMARD Patients who fail a first TNFinhibitor may be switched to a differ-ent TNF inhibitor11 Treatment with tofacitinib can beconsidered after patients fail treatmentwith biological DMARDs12 For patients in persistent remis-sion first taper down the corticos-teroid dosage If remission persistsconsider tapering down treatmentwith any biological DMARD espe-cially if the patient is also receivingone or more synthetic DMARDs13 In patients with sustained long-term remission consider taperingdown the dosage of conventional syn-thetic DMARDs as a shared decisionbetween the patient and physician14 When adjusting therapy take intoaccount progression of structuraldamage comorbidities and safety is-sues as well as disease activity

Source Dr Smolen

Summary of EULARrsquos 2013 RA Management Recommendations


THE EULAR REPORT 2013 5

ACR recommendations specified anti-TNF drugs as an option for initial thera-py of patients with high disease activityand poor prognostic features as well aslow disease activity patients who get in-adequate benefit from syntheticDMARDs In the ACR recommenda-tions abatacept as well as rituximab felllower in the management algorithmwhile tocilizumab was completely offthe page

Not only do the new EULAR recom-mendations place tocilizumab and abata-cept on the same level as the TNFinhibitors the EULAR draft further sin-gles out tocilizumab as the ldquopreferredagentrdquo for patients who must receive a bi-ologic DMARD as monotherapy ratherthan the preferred way in combinationwith methotrexate ldquoPreference is givento combining all biologicals withmethotrexaterdquo Dr Smolen said The re-vision also cites rituximab as another bi-ologic DMARD to consider but itrsquos notranked as high as the others

In another change from 2010 the taskforce specially noted the potential ben-efit from using multipleconventional syntheticDMARDs for initial treat-ment ldquoThe 2013 task forcereiterates the evidence-based view that conven-tional synthetic DMARDmonotherpy is effectivebut based on some newertrial data on conventionalsynthetic DMARD combi-nation therapy the taskforce more explicitly en-dorses combination ofconventional synthetic DMARDs earlyon Preference to combination is notgiven because of possible limitations inthe design of these trials and conflictingtrial datardquo

The 2013 recommendations also spec-ify a role for tofacitinib Dr Smolenhighlighted that the task force reacheda consensus on how to fit tofacitinib intothe treatment algorithm in early Aprilbefore the European Medicines Agency

denied the drug European marketing ap-proval in late April Despite the drug be-

ing turned down as atreatment option for Eu-ropean patients ldquothe taskforce was convinced ofthe clinical functionaland structural efficacy oftofacitinib based on avail-able evidencerdquo Howeverciting a possibly higherrisk for flare of herpeszoster compared with bi-ologic DMARDs the taskforce said that tofacitinibshould be used only in pa-

tients who had failed at least one biolog-ic drug and ldquopreferably twordquo until moreexperience and registry data becameavailable

Dr Smolen said he has been a consult-ant to a speaker for or has received grantsupport from 14 pharmaceutical compa-nies He also said he served as the princi-pal investigator for seven trials that assessedsix different biologic agents for the treat-ment of rheumatoid arthritis

Continued from previous page

DR JOSEF S SMOLEN

Abatacept Adalimumab Equivalent for RAin 2-Year Head-to-Head Trial

B Y B I A N C A N O G R A DY

A2-year head-to-head comparison ofabatacept and adalimumab in

rheumatoid arthritis patients who wereon background methotrexate has foundequal improvement with both biologicsaccording to results from a study present-ed at the Congress

The randomized investigator-blindedAMPLE trial is the first 2-year compara-tor study of biologics done in biologic-naive rheumatoid arthritis patients

ldquoThrough 2 years of treatment in thisfirst active comparator study between bi-ologic agents in rheumatoid arthritis pa-tients with an inadequate response tomethotrexate this robust data set demon-strates that subcutaneous abatacept andadalimumab were equally efficacious inclinical functional and radiographic out-comesrdquo said Dr Michael H Schiff a pro-fessor of medicine at the University ofColorado Denver

Click here to view a video interview with Dr Michael H Schiff

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Researchers recruited 646 patients withactive RA and an inadequate response tomethotrexate and randomized them to ei-ther 125 mg of abatacept weekly (withoutan IV load) or 40 mg of adalimumab bi-weekly with a stable dose of methotrexate

The data show that both agents have anexcellent retention rate with 79 of theabatacept and 65 of the adalimumabgroups completing the 2-year follow-up

The two medications showed similarefficacy for American College ofRheumatology (ACR) 20 50 70 and 90responses and rates of remission on theDisease Activity Score-28 (DAS28) DrSchiff said For ACR 20 the 2-year re-sponse rate was 60 in each group TheACR 50 response rate was 47 for theadalimumab group and 45 for theabatacept group For the ACR 70 therates were 29 for adalimumab and31 for abatacept and for the ACR 90the rates were 8 for adalimumab and15 for abatacept

The 2-year DAS28 rate was virtuallyidentical in each group with a mean de-crease of about 22 from baseline X-raynonprogression was seen in 84 of eachgroup at 2 years Dr Schiff said

The study found similar numbers of se-rious adverse events in both arms (14 of

the abatacept group and 17 of the adal-imumab group) However serious ad-verse events leading to discontinuation ofthe study medication occurred in 5 ofpatients taking adalimumab and 2 ofthose taking abatacept

There was one death in each group ndashneither of which was related to the studydrugs There were seven malignancies ineach group four patients in each groupdiscontinued their study medication be-cause of neoplasm

Infections were the most common se-rious side effects (31 total) occurring in4 of the abatacept and 6 of the adal-imumab groups) There were eight op-portunistic infections ndash four in eachgroup The adalimumab group had twocases of pulmonary tuberculosis onecase of disseminated tuberculosis andone case of disseminated histoplasmosisThere were three cases of pneumonia inthe abatacept group and four in theadalimumab group

Autoimmune events were also relative-ly common ndash 18 in all with 12 in the abat-acept group (4) and 6 in theadalimumab group (2) Dr Schiff saidnone of these were serious or clinicallyimportant

During the question-and-answer peri-od Dr Schiff said itrsquos not currently pos-sible to predict which patients would

respond to the drugs ldquoWe looked at re-sponders in both groups and were notable to differentiate them based on clini-cal characteristicsrdquo he said ldquoWe are nowanalyzing the biomarkers and hope tohave that information for EULAR 2014rdquo

ldquoEULARACR guidelines recommendstarting a patient on methotrexate andthen optimizing the dose over 3-6months and if a patient has an incom-plete response to methotrexate then toadd a biological agentrdquo said Dr Schiff inan interview

He noted that anti-tumor necrosis factor(anti-TNF) agents have been the first choiceof most rheumatologists and adalimum-ab is the most widely chosen anti-TNFagent worldwide which is why it was se-lected as one of the agents for the head-to-head trial Abatacept employs anothermethod of action T-cell inhibition

ldquoThis paper has important clinical sig-nificance because a patient and his orher rheumatologist want to have data tomake an informed choice of a biologicagent to add when an incomplete re-sponse to methotrexate occursrdquo he said

Dr Schiff disclosed that he is a consult-ant and speaker for Bristol-Myers Squibband AbbVie

Senior writer Michele G Sullivancontributed to this report




Synthetic Triple Therapy Matches Anti-TNFTherapy in Rheumatoid Arthritis


When rheumatoid arthritis pa-tients fail initial treatment withmethotrexate monotherapy

are they better served by a less expensivestep-up treatment or the one thatmay better slow their radiographic progression and pro-duce faster responses

That seems to be the choice be-tween step-up from methotrexatemonotherapy by adding syntheticdisease-modifying antirheumaticdrugs (DMARDs) such as sul-fasalazine and hydroxychloroquineor by adding a tumor necrosis factor(TNF) inhibitor such as etanercept

The RACAT (Rheumatoid Arthri-tis Comparison of Active Thera-pies) trial tested those two options in 353rheumatoid arthritis (RA) patients at 36US or Canadian sites between July 2007and December 2010 The studyrsquos primaryendpoint improvement in average diseaseactivity score in 28 joints (DAS28) frombaseline to 48 weeks of treatment wassimilar in both treatment arms provingthe noninferiority of the triple syntheticDMARD regimen against the etanerceptbiological arm Dr James R OrsquoDell re-ported in a poster at the Congress The re-sults also appeared online simultaneouslywith Dr OrsquoDellrsquos poster presentation (NEngl J Med 2013 June 11 [doi 101056NEJMoal1303006])

ldquoWe showed that starting first with aTNF inhibitor or first with triple therapy re-sulted in the same outcomes But costswere not the same We [successfully] treat-ed another 30 of patients who did notneed a biologicrdquo with the synthetic tripletherapy ldquoAnd in the patients where tripletherapy doesnrsquot work you can changethem to a biologic and they have identicaloutcomes clinically by DAS28 and ra- diographicallyrdquo compared with patientswho began on etanercept added tomethotrexate from the start he said DrOrsquoDell is chief of rheumatology at the VAMedical Center in Omaha Neb and pro-fessor of medicine at the University of Ne-braska

ldquoNothing is lost for the patient if they

donrsquot do well on triple therapy they canswitch to a biological The data are persua-sive and the economic case is easy to makeYou absolutely ought to go with triple ther-apyrdquo he concluded based on the study find-ings

But ldquoit is very difficult to get physiciansto buy into thisrdquo strategy he said in an in-terview TNF inhibitors such as etanerceptand other biological DMARDs are ldquoseduc-tiverdquo Dr OrsquoDell said because they are ef-fective work quickly and appear moreldquotargetedrdquo than synthetic DMARDs andthey are promoted by well-financed mar-keting campaigns

Dr OrsquoDell conceded that the study datashowed a signal of more radiographic pro-gression with triple synthetic DMARDtreatment that could potentially over timeaccrue to more substantial differences At48 weeks after the onset of treatment pa-tients on triple therapy had an average054-point increase (worsening) in their vander Heijde modified Sharp score com-pared with an average 029-point rise in thepatients who received etanercept a 025-point average difference in favor of etaner-cept that did not reach statisticalsignificance But this trend toward greaterradiographic progression in patients ontriple therapy was consistent with the sta-tistically significant roughly 1-point averageadditional increased radiographic progres-sion with triple therapy compared with pa-tients on methotrexate plus etanerceptthat was seen after 2 years of follow-up inthe TEAR (Treatment of Early AggressiveRheumatoid Arthritis) trial (ArthritisRheum 2012642824-35)

The TEAR study which enrolled pa-

tients with very early RA included a sub-group with an inadequate response tomethotrexate monotherapy and in thatsubgroup patients randomized to tripletherapy and those randomized to etaner-cept plus methotrexate had similar clinical

outcomes consistent with the newstudy findings

ldquoItrsquos hard to say that 1 or 2 units onthe Sharp score doesnrsquot matter mucheven if you donrsquot see the differencefor several yearsrdquo commented DrDaniel Furst professor of medicineand director of the RheumatologyClinical Research Center at the Uni-versity of California Los Angeles

ldquoTriple therapy is effective clini-cally but it doesnrsquot do so well for x-rays There are relationshipsbetween a 1 or 2 Sharp score differ-

ence and long-term outcomes Across theboard with biologics the difference is 1 or2 Sharp units If onersquos philosophy is to hitthe RA hard and stop it then perhaps a bi-ologic is betterrdquo Dr Furst commented inan interview

But another view was that triple therapycould play a useful and cost-effective roleThe new findings along with the TEAR re-sults make ldquoinitial treatment of early RAwith triple therapy a reasonable approachrdquosaid Dr Joel M Kremer a professor ofmedicine at Albany (NY) Medical Collegeand director of research at the Center forRheumatology in Albany The only cleardownside is that if triple therapy doesnrsquotwork the patient loses time but thatrsquos truefor every treatment option he noted

ldquoWe donrsquot usually have the opportunityto hear the data for generic drugsrdquo as muchas for brand-name formulations Dr Kre-mer said in an interview ldquoWill data like thissubstantially change prescribing patternsProbably not but what might happen isthat insurers may look at these data and saythat patients should fail triple therapy be-fore starting a biologic That would be a seachangerdquo for rheumatology he added

ldquoI have always used methotrexate firstusually in combination with hydroxy-chloroquinerdquo Dr Kremer said He hasnot usually also prescribed sulfasalazinebut said he would consider adding it

DR DANIEL FURST DR EDWARD C KEYSTONE




based on the new dataThe new study enrolled patients with

a DAS28 score of 44 or higher despite atleast 12 weeks of stable methotrexatetherapy with a weekly dosage of 15-25mg The patients averaged about 57 yearsold After the first 24 weeks on random-ized treatment patients who did not havea decrease in their DAS28 of at least 12units switched to the alternative regi-mens The primary outcome was changein DAS28 at week 48 according to initialtreatment assignment the researcherscollected 48-week DAS28 scores from 309enrolled patients The mean change inDAS28 from baseline at 48 weeks was a212-unit reduction in the triple-therapypatients and a 229-unit reduction in theetanercept patients an average 017-unitdifference between the two treatmentarms that was not statistically significantand that fell within the studyrsquos prespeci-fied range for noninferiority for tripletherapy

A similar percentage of patients 27 ineach of the treatment arms switched to thealternative therapy at 24 weeks because ofa lack of an adequate initial responseThere were also no statistically significant

differences between the treatment arms intheir rate of American College of Rheuma-tology (ACR) 20 and 50 responses at both24 and 48 weeks

The results showed significant differ-ences between the treatment arms after thefirst 24 weeks of treatment for higher-lev-el responses For example the percentageof patients achieving an ACR 70 responsewas 5 in the triple-therapy patients and16 in the etanercept patients a statistical-ly significant difference The rate of pa-tients with a DAS28 score of 26 points orless at 24 weeks was 13 in the triple-ther-

apy patients and 22 in those on etaner-cept a significant difference

Based on findings like these ldquoI wouldstart a biologic in a patient who failedhigh-dose methotrexate and had poorprognostic factors and highly active dis-ease because at 6 months etanercepthad the edgerdquo said Dr Edward C Key-stone director of the Centre for Arthri-tis and Autoimmune Disease at MountSinai Hospital in Toronto and a coinves-tigator on the new study But for all theother patients ldquowhy not start on tripletherapy first if you can switch them lat-er if needed and the patients do wellrdquohe asked ldquoThe important observation isthat the same percentage of patientsfailed in each arm That is a huge mes-sagerdquo

The RACAT study received no com-mercial support Dr OrsquoDell said that hehad no disclosures Dr Furst has been aconsultant to or received grant supportfrom Abbott Amgen Bristol-MyersSquibb and other companies Dr Kremerhas been a consultant to or received grantsupport from Pfizer Abbott Genentechand other companies Dr Keystone saidthat he has been a consultant to or has re-ceived research grants from Amgen Pfiz-er Merck and other companies


Dr James R OrsquoDell at the EULAR Congress

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Proposed ACR-EULAR SclerodermaClassification Criteria Are More Inclusive

B Y S A R A F R E E M A N

New classification criteria for sclero-derma presented at the Congresscorrectly identify more patients

who could potentially be included in epi-demiological studies and clinical trials thanis possible with existing classification sys-tems

The new system is still a proposal and isunder review by the European LeagueAgainst Rheumatism (EULAR) and theAmerican College of Rheumatology(ACR) according to Dr Frank van denHoogen who is the director of the rheuma-tology center at Sint Maartenskliniek inNijmegen and head of the department ofrheumatology at Radboud University inNijmegen both in the Netherlands

In a validation cohort the ACR-EULARcriteria had a sensitivity of 91 and a speci-ficity of 92 to correctly identify patientswith systemic sclerosis (SSc) By compari-son the 1980 Preliminary ARA Criteria hada sensitivity of 75 and a specificity of72

The whole process of developing theACR-EULAR criteria has taken about 5years Dr van den Hoogen explained in aninterview ldquoThe ARA criteria were not assensitive as we wanted because they exclud-ed some patients with limited disease andalso patients with newly diagnosed dis-easerdquo he added

ldquoThe purpose of classification criteria isto include similar patients in researchrdquo Drvan den Hoogen said ldquoClassification crite-ria are not synonymous with diagnostic cri-teriardquo he explained ldquo[they] are generallymore standardized and less inclusiverdquo Thisis because physicians will see patients withmultiple symptoms and it would not bepossible to include every symptom seen inroutine practice in a set of classification cri-teria Nevertheless diagnostic criteria dotend to mirror classification criteria

The process of determining which itemsto include was driven by both data and con-sensus Delphi exercises and a nominalgroup technique were used to create a setof potential items for SSc classification

Several patient cases were then reviewedby leading scleroderma experts based in Eu-rope and North America The cases repre-

sented the full spectrum of systemic scle-rosis including those with a low and thosewith a high probability of having the dis-ease Experts ranked the importance ofthe symptoms exhibited by each of thesecases and a whittled down list with a scor-ing system was obtained SSc was presentwith a score of 9 or more

Skin thickening of the fingers of bothhands extending past the metacarpopha-langeal (MCP) joints was considered to beindicative of scleroderma and was given ascore of 9 Conversely patients with skin in-

volvement likely to be due to another scle-roderma-like disorder or skin thickeningsparing the fingers were not likely to haveSSc

Other items included skin thickening ofthe fingers with subitems of puffy fingers(score = 2) and whole finger skin thicken-ing distal to the MCP (4) fingertip le-sions with subitems of digital tip ulcers(2) and pitting scars (3) telangiectasia (2)abnormal nailfold capillaries (2) pul-monary arterial hypertension interstitiallung disease or both (2) Raynaudrsquos phe-nomenon (3) and the presence of anyscleroderma-related autoantibodies (3)

The ability of these criteria to correctlyidentify patients with and without SSc wasthen prospectively tested in a random sam-

ple of 200 individuals and further validat-ed in a cohort of 405 individuals that includ-ed both early and prevalent cases ofscleroderma and its mimics

ldquoThe proposed ACR-EULAR criteria forthe classification of [SSc] should allowmore patients to be classified correctly as[SSc]rdquo including those with early (less than3 years) scleroderma and the 20 of pa-tients who have limited disease but who donot meet current classification criteria Drvan den Hoogen said

ldquoNew ACR [EULAR] criteria show in-

creased sensitivity in comparison to the old[ARA] criteriardquo concurred Dr Suzana Jor-dan of University Hospital Zurich Shepresented findings on the use of the pro-posed system in 317 patients mainly withearly or mild disease from the Zurich scle-roderma cohort

Applying the criteria to this Swiss patientpopulation Dr Jordan noted that ldquo75 of[SSc] patients were correctly identifiedcompared to just over half of all patients(51) using the ARA criteriardquo Further-more ldquo50 of early scleroderma patientswho did not fulfill the old criteria met thenewrdquo she concluded

Dr van den Hoogen said that he had nodisclosures except that this work was fund-ed jointly by EULAR and the ACR

Click here to view a video interview with Dr Frank van denHoogen

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427HQ13PR00381 Date of Preparation August 2013 EUOC-138524-01

ORENCIAreg (abatacept) PRESCRIBING INFORMATION See Summary of Product Characteristics

before prescribing PRESENTATION 250 mg powder for concentrate for solution for IV infusion

containing 250 mg abatacept per vial Each ml contains 25 mg of abatacept after reconstitution

125 mg pre-filled syringe for SC injection Each pre-filled syringe contains 125 mg of abatacept in

1 ml INDICATION Rheumatoid arthritis (IV infusion and SC pre-filled syringe) Treatment of

moderate to severe active rheumatoid arthritis (RA) in combination with methotrexate in adult

patients who have responded inadequately to previous therapy with one or more disease-modifying

anti-rheumatic drugs (DMARDs) including methotrexate (MTX) or a Tumour Necrosis Factor (TNF)

-alpha inhibitor A reduction in the progression of joint damage and improvement of physical function

have been demonstrated during combination treatment with abatacept and methotrexate See

SmPC Polyarticular Juvenile Idiopathic Arthritis (pJIA) IV infusion only Orencia 250 mg powder

for concentrate for solution for infusion is indicated for treatment of moderate to severe active pJIA in

paediatric patients 6 years of age and older who have had an insufficient response to other DMARDs

including at least one TNF inhibitor DOSAGE and ADMINISTRATION Treatment should be initiated

and supervised by specialist physicians experienced in the diagnosis and treatment of RA Orencia

250 mg powder for concentrate for solution for IV infusion Adults and elderly Patients weighing

lt 60 kg 500 mg (2 vials) Patients weighing ge 60 kg to le 100 kg 750 mg (3 vials) Patients weighing

gt 100 kg 1000 mg (4 vials) Treatment of pJIA Paediatric patients 6 to 17 years of age weighing

less than 75 kg 10 mgkg paediatric patients weighing 75 kg or more to be administered adult

dosage not exceeding a maximum dose of 1000 mg See SmPC for details of reconstitution and

administration as a 30 minute IV infusion After initial administration Orencia should be given at

2 and 4 weeks then every 4 weeks thereafter Children Use in children below 6 years of age is

not recommended Orencia 125 mg solution for injection (SC pre-filled syringe) Adults and elderly

Treatment should be initiated with a loading dose using an intravenous infusion Following this

loading dose the first 125 mg subcutaneous injection of Orencia should be given within a day then

125 mg subcutaneous injections once weekly Patients who are unable to receive an infusion may

initiate weekly injections of subcutaneous Orencia without an intravenous loading dose Patients

transitioning from Orencia IV therapy to SC administration should administer the first subcutaneous

dose instead of the next scheduled intravenous dose Children Administration in children below

18 years of age is not recommended The continuation of treatment with abatacept should be

re-assessed if patients do not respond within 6 months CONTRAINDICATIONS Hypersensitivity

to the active substance or excipients Severe and uncontrolled infections such as sepsis and

opportunistic infections WARNINGS AND PRECAUTIONS Allergic Reactions Caution in patients

with a history of allergic reactions Anaphylaxis or anaphylactoid reactions can occur and can

be life threatening Orencia should be discontinued permanently if a patient develops serious

allergic or anaphylactic reaction Infections Caution should be exercised when considering the

use in patients with a history of frequent infections or underlying conditions which may prompt to

infection Treatment with Orencia should not be initiated with patients with active infections until

infections are controlled Screening for tuberculosis and hepatitis B should be performed prior to

therapy Any patient who develops a new infection should be closely monitored and Orencia should

be discontinued if a patient develops a serious infection Monitor patients for signs of infection

when transitioning from TNF-antagonist to Orencia Co-administration of Orencia with biologic

immunosuppressive or immunomodulatory agents could potentiate the effects of abatacept on the

immune system Treatment with immunosuppressive therapy may be associated with progressive

multifocal leukoencephalopathy (PML) Orencia treatment should be discontinued if neurological

symptoms suggestive of PML occur and appropriate diagnostic measures initiated Malignancies

The potential role of Orencia in the development of malignancies is unknown see SmPC Elderly

Caution should be used when treating elderly patients due to a higher incidence of infections and

malignancies in this patient group Autoimmune processes Theoretical risk of deterioration in

autoimmune disease Immunisation Live vaccines should not be given simultaneously or within

3 months of discontinuation of Orencia See SmPC DRUG INTERACTIONS Concomitant therapy

of Orencia with a TNF-inhibitor is not recommended No major safety issues were identified

with the use of Orencia in combination with sulfasalazine hydroxychloroquine or leflunomide

PREGNANCY AND LACTATION Do not use in pregnancy unless clearly necessary Women should

use contraception and not breast-feed during treatment and for up to 14 weeks after last dose

treatment UNDESIRABLE EFFECTS In adult placebo-controlled trials the following adverse

drug reactions were reported Very Common (ge 110) upper respiratory tract infection including

tracheitis nasopharyngitis Common (ge 1100 to lt 110) Lower respiratory tract infection (including

bronchitis) urinary tract infection herpes infections (including herpes simplex oral herpes and

herpes zoster) rhinitis pneumonia influenza leukopenia headache dizziness paraesthesia

conjunctivitis hypertension flushing blood pressure increased cough abdominal pain diarrhoea

nausea dyspepsia mouth ulceration aphthous stomatitis vomiting liver function test abnormal

(including transaminases increased) rash (including dermatitis) alopecia pruritus pain in

extremity fatigue asthenia injection site reactions Uncommon (ge 11000 to lt 1100) Tooth

infection onychomycosis sepsis musculoskeletal infections skin abscess pyelonephritis pelvic

inflammatory disease basal cell and squamous cell carcinoma skin papilloma thrombocytopenia

hypersensitivity depression anxiety sleep disorder (including insomnia) migraine dry eye visual

acuity reduced vertigo palpitations tachycardia bradycardia hypotension hot flush vasculitis

blood pressure decreased bronchospasm wheezing dyspnea gastritis increased tendency to

bruise dry skin urticaria psoriasis erythema hyperhidosis arthralgia amenorrhea menorrhagia

influenza like illness weight increased Rare (ge 110000 to lt 11000) Tuberculosis bacteraemia

gastrointestinal infection lymphoma lung neoplasm malignant throat tightness See SmPC for

further details LEGAL CATEGORY POM MARKETING AUTHORISATION NUMBER AND BASICNHS PRICE Orencia 250 mg concentrate for solution for infusion - EU107389001 1 vial pack

pound30240 Orencia 125 mg solution for Injection - EU107389008 4 pre-filled syringes with needle

guard pound120960 MARKETING AUTHORISATION HOLDER Bristol-Myers Squibb Pharma EEIG

Uxbridge Business Park Sanderson Road Uxbridge Middlesex UB8 1DH Tel 0800-731-1736

DATE OF PREPARATION April 2013 Job No 427UK13PR03910

Adverse events should be reported Reporting forms and information can be found at wwwmhragovukyellowcard

Adverse events should also be reported to Bristol-Myers Squibb Pharmaceuticals Ltd

Medical Information on 0800 731 1736 or medicalinformationbmscom

Annual PAH Screening Recommended forSystemic Sclerosis Patients


Patients with systemic sclerosisshould undergo annual screeningfor pulmonary arterial hyperten-

sion using a combination of transtho-racic echocardiography and pulmonaryfunction tests an international expertpanel said

These are the first evidence- and consen-sus-based recommendations for pulmonaryarterial hypertension (PAH) screening in pa-tients with systemic sclerosis and the pan-el also called for screening patients withmixed or other connective tissue diseaseswith scleroderma features ldquoOur hope isthat these recommendations will lead toearlier detection of PAH in connective tis-sue diseases and improve patient out-comesrdquo Dr Dinesh Khanna said whilepresenting the screening recommendationsat the Congress

About 5-15 of patients with sys-temic sclerosis develop PAH and oncePAH occurs up to 30 of patients will

die within 3 years said Dr Khanna di-rector of the scleroderma program atthe University of Michi-gan Ann Arbor

ldquoDespite having ap-proved drugs availablerdquo totreat systemic sclerosis andother scleroderma-spec-trum disorder connectivetissue diseases these treat-ments ldquohave not had ahuge impact on survivalThe only thing we can of-fer patients is screeningfollowed by early diagnosisand treatmentrdquo Dr Khan-na said in an interview

The new recommendations say thatpatients with a tricuspid regurgitant ve-locity measured by transthoracicechocardiography greater than 28 msrequire assessment for PAH by rightheart catheterization Right heartcatheterization is also needed for pa-tients with a tricuspid regurgitant veloc-

ity of 25-28 ms if they also have signsor symptoms of PAH such as dyspnea

fatigue chest pain dizzi-ness loud pulmonarysound or peripheral ede-ma Another echo findingthat should trigger rightheart catheterization re-gardless of signs or symp-toms or tricuspidregurgitation is right atrialor ventricular enlarge-ment

The key measures onpulmonary function teststhat trigger right heart

catheterization is a forced vital capacity(FVC) to diffusion capacity of lungs forcarbon monoxide (DLCO) ratio of morethan 16 or a DLCO of less than 60 ifeither appears in the setting of PAHsigns or symptoms Alternatively meet-ing either of these pulmonary criteriashould lead to right heart catheterization

DR HEATHER GLADUE

Continued on page 12


Early Effective Sustained12

EUOC

-K000

3A 0

413

427

HQ13

PR00

381

The first and onlyselective T-cellco-stimulationmodulatorapproved forthe treatmentof RA14-7

Now available inboth IV and SC formulations1

NEWSUBCUTANEOUS FORMULATION1

Prescribing Information can be found overleaf RA Rheumatoid arthritis References 1 Bristol-Myers Squibb ORENCIAreg (abatacept) SmPC 2012 2 Weinblatt ME Schiff M Valente R et al Arthritis Rheum 201365(1)28-38 3 Thaler KJ Gartlehner G Kien C et al

Drug Class Review Targeted Immune Modulators Final Update 3 Report [Internet] Portland (OR) Oregon Health amp Science University 2012 Mar 4 Choy EH Clin Exp Rheumatol 200927(3)510-518 5 Moreland LW Alten RVan den Bosch F et al Arthritis Rheum 200246(6)1470-1479 6 Emery P Expert Opin Investig Drugs 200312(4)673-681 7 Weisman MH Durez P Hallegua D et al J Rheumatol 200633(11)2162-2166



regardless of signs and symptoms if thepatientrsquos most recent blood level of N-terminal pro-brain natriuretic peptide(NT-ProBNP) was greater than twicethe upper limit of normal

The panel also said that patients shouldundergo right heart catheterization re-gardless of PAH signs and symptoms ifthey fulfill the screening algorithm devel-oped for the DETECT study (AnnRheum Dis 2013 May 18 [doi101036annrheumdis-2013-203301])

The panel recommended annualtransthoracic echo and pulmonary func-tion test screening or more frequentlyif a patient shows new signs or symp-toms Measurement of NT-ProBNPshould happen at baseline and then berepeated if new signs or symptoms ofPAH appear They also recommendedapplying the full DETECT screening al-gorithm in patients diagnosed with sys-temic sclerosis or other sclerodermaspectrum connective-tissue disease formore than 3 years and a DLCO that isless than 60 Right heart catheteriza-tion is mandatory to definitively diag-nose PAH Dr Khanna stressed Thepanel also said screening is not neededin patients with mixed- or other connec-tive tissue disorders who did not havescleroderma-like features

In a separate report at the meeting DrKhanna and his associates assessed theability of transthoracic echocardiogra-phy and pulmonary function tests toscreen patients with PAH They useddata from 69 patients with PAH in twoseparate reported series that togetherhad 347 patients with systemic sclerosis

who underwent assessment for suspect-ed PAH ( J Rheumatol 2011382172-9and J Rheumatol 2010372290-8)

The new retrospective analysis showedthat combining transthoracic echo andpulmonary function test screens can havea negative predictive accuracy of 98 forcorrectly ruling out PAH in patients withsystemic sclerosis reported Dr HeatherGladue a rheumatology fellow at theUniversity of Michigan

The recommendations panel cau-tioned that its proposals should not sub-stitute for individualized directassessment of each patient The panelalso noted that the cost-effectiveness ofits recommendations had not yet beenassessed In addition to representatives

from the University of Michigan thetask force included members from theUniversity of California Los AngelesMassachusetts General HospitalBoston Stanford (Calif) University theUniversity of Zurich University Hospi-tal in Lille France the University ofParis-South McGill University Montre-al Johns Hopkins University Baltimoreand St Joseph Hospital Phoenix

The task force was supported by the Scle-roderma Foundation and the PulmonaryHypertension Association Dr Khanna saidthat he has been a consultant to severaldrug companies including Actelion BayerGenentechRoche Gilead Merck andDIGNA Dr Gladue said that she had nodisclosures

Continued from page 10

Click here to view a video interview with Dr Dinesh Khannaabout the PAH screening recommendations

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More Evidence Shows That TNF InhibitorsAre Associated With Reduced Diabetes Risk

B Y J E N N I E S M I T H

Recent research has suggested thattumor necrosis factor inhibitorscan significantly reduce diabetes

risk in people with rheumatoid arthritis Dr Siri Lillegraven of Diakonhjem-

met Hospital in Oslo presented resultsfrom the CORRONA (Consortium ofRheumatology Researchers of NorthAmerica) study which Dr Lillegravenits lead author called ldquothe first largestudy to find the same associationrdquo atthe Congress The study used COR-RONA registry data from 22943 pa-tients and about 22000 RA treatmentregimens with a mean duration between15 and 24 years

Dr Lillegraven and her colleagues foundan adjusted hazard ratio for type 2 diabetesof 035 for TNF inhibitors (95 confidenceinterval 013-091) compared with a refer-ence group of nonmethotrexate nonhy-droxychloroquine nonbiologic disease-modifying antirheumatic drugs such as cy-closporine sulfasalazine and leflunomideThe disease-modifying antirheumatic drugs(DMARDs) hydroxychloroquine andmethotrexate were separately comparedwith this reference group

ldquoIt was a statistically significant find-ing and the model was adjusted for dif-

ferences between patients who receivedTNF inhibitors and the patients who re-ceived the comparator drugsrdquo Dr Lille-graven said in an interview

One of Dr Lillegravenrsquos coauthors onthe study Dr Daniel Solomon ofBrigham and Womenrsquos Hospital inBoston earlier reported a lower risk oftype 2 diabetes for individuals takingTNF inhibitors or hydroxychloroquinecompared with nonbiologic DMARDs( JAMA 20113052525-31)

In that study which enrolled about14000 patients and evaluated about22000 treatment episodes the multi-variate adjusted hazard ratio for dia-betes was 062 (95 confidence interval042-091) for TNF inhibitors comparedwith other nonbiologic DMARDs Theeffect was even greater for hydroxy-chloroquine compared with other non-biologics (HR 054 95 CI 036-080)

Dr Lillegraven and her colleagues sawa similar effect size for hydroxychloro-quine compared with the nonbiologicDMARDs but this did not reach statis-tical significance

As both studies were observational indesign Dr Lillegraven noted the resultsdo not carry the weight of randomizedcontrolled trial findings ldquoWe wouldhave loved to have a clinical trial that

confirmed the findingsrdquo she said addingthat designing such a trial would be dif-ficult ldquoThe outcome is relatively rareand you will not likely get enough dia-betes outcomes to be able to concludewhether an exposure had an effectrdquo InDr Lillegraven and her colleaguesrsquostudy for example only 84 incident cas-es of diabetes occurred

Last year investigators reported thatTNF inhibitors were associated with ahalving of diabetes risk compared withRA patients who had never used them(HR 049 95 CI 024-099) in a cohortof 1587 RA patients without diabetes atenrollment who were followed for 3-4years (Arthritis Care Res 201264215-21) and several studies have suggested arelationship between the biologic path-ways that TNF inhibitors affect and dia-betes

Dr Lillegraven also analyzed the im-pact of body-mass index and steroiddosage on diabetes incidence in these pa-tients Those with a BMI of more than30 kgm2 had a statistically significantsixfold increased rate of incident dia-betes compared with patients with aBMI of less than 25 kgm2 Patientswith a BMI of 25-30 kgm2 had a signif-icant nearly twofold increased rate Pa-tients who received a steroid dose of atleast 75 mgday had a statistically signif-icant twofold increased diabetes inci-dence compared with patients who didnot receive any steroid treatment

Dr Lillegraven said that her studyrsquosfindings added to the earlier findingssupport ldquoa potential for tailoring treat-ment in high-risk individualsrdquo But it isstill too early to draw any definite con-clusions regarding how this should becarried out in the clinic she cautioned

Dr Lillegraven declared no conflicts ofinterest relevant to her study DrSolomon declared unpaid consultanciesfor Pfizer and Novartis Three othercoauthors reported financial relation-ships with pharmaceutical firms andCORRONA a database registry forrheumatologic diseases one is an em-ployee of CORRONA

Click here to view a video interview with Dr Siri Lillegraven

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MRI Scoring System for Joint-Space Narrowing Has Research Promise in RA

B Y E L I Z A B E T H M E C H C AT I E

Amagnetic resonance imaging scor-ing system of joint-space narrow-ing in rheumatoid arthritis showed

ldquoa very highrdquo agreement with computedtomography scores and may become auseful tool in rheumatoid arthritis clinicaltrials after further validation judgingfrom data presented by Dr Uffe MoslashllerDoslashhn

In a small study which was conduct-ed to validate theOMERACT-RAMRISMRI JSN scoring systemin the wrists andmetacar pophalangeal(MCP) joints there wasa very high agreementbetween the joint-spacenarrowing scores onMRI and CT and moder-ate agreement betweenscores on MRI and x-raysaid Dr Moslashller Doslashhn ofCopenhagen UniversityHospital at Glostrup atthe Congress In addi-tion there was ldquohigh tovery highrdquo inter- and in-trareader reliability par-ticularly for the wristjoints

An OMERACT (Out-come Measures inRheumatology) initia-tive this scoring systemis being developed to provide a moreprecise and sensitive method of meas-uring joint space damage in patientswith rheumatoid arthritis (RA) but itneeds to be validated through compar-isons to other imaging methods

To evaluate the degree of agreementwith CT and x-ray scores this study as-sessed MRI and CT images of the wrist

and the second to fifth metacarpopha-langeal (MCP 2-5) joints of 14 peoplewith RA and one healthy control whowere from a clinical trial Three readersassessed the images twice and a singlereader scored x-rays using the Sharp-Vander Heidje method said Dr MoslashllerDoslashhn who is in the center for rheuma-tology and spine diseases at the hospital

The MRI scores of joint space narrow-ing ldquowere very highly correlatedrdquo withCT scores when comparing the wrist

and MCP scores both separately andcombined Using intraclass correlationcoefficients (ICCs) as a measure ofagreement between scores and scorersthe MRI and CT scores for joint spacenarrowing were 094 for the MCP joints092 for the wrist and 092 for the wristand MCP joints combined But the ICCsfor the x-ray joint space narrowing

scores were lower With MRI scoresthe ICCs were 049 for the MCP 2-5joints and 055 for the wrist With CTscores the ICCs were 056 for the MCP2-5 joints and 043 for the wrist

ldquoThe most important next step is totest the scoring system in a longitudi-nal setting in order to investigate thesensitivity to changerdquo Dr Moslashller Doslashhnsaid in an interview ldquoBefore the systemcan be implemented as an outcomemeasure in clinical trials we need to

know if it is more sensitive than othermethods that are already available If itturns out that [joint space narrowing]assessment of several joints on x-ray isjust as good as ndash or better than ndash MRIthen it does not add information towhat we already use todayrdquo

Dr Moslashller Doslashhn reported that he hadno relevant financial disclosures

The MRI scores of joint space narrowing ldquowere very highly correlatedrdquo with CT scores whencomparing the wrist and MCP scores both separately and combined

PH

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Algorithm Helps to DETECT PulmonaryArterial Hypertension in Systemic Sclerosis


The use of a two-step algorithm sig-nificantly increased the rate atwhich pulmonary arterial hyper-

tension was diagnosed in patients withsystemic sclerosis in aprospective observationalcross-sectional study

The results of the DE-TECT study presented atthe Congress showed thatthe two-step algorithm hada sensitivity of 96 for cor-rectly identifying the condi-tion which was higher thanthe 71 sensitivity obtainedusing methods recom-mended currently by theEuropean Society of Cardi-ologyEuropean Respiratory Society(ESCERS) guidelines The ESCERS rec-ommendations are mainly based on con-sensus rather than robust evidence andfocus on the use of transthoracic echocar-diography

ldquoDETECT is unique because it showsthat if you just do an echocardiogram thatyou miss 29 of people who subsequent-ly have pulmonary arterial hypertension[PAH] whereas if you apply the DE-TECT algorithm you miss only 4 of thepeoplerdquo Dr Dinesh Khanna director ofthe scleroderma program at the Univer-sity of Michigan Ann Arbor said in an in-terview

Dr Khanna who was a coinvestigator inthe study added ldquoPAH is a leading causeof mortality it has high prevalence [and]it has a median survival of 2-3 years hellip Youdonrsquot want to miss these patientsrdquo DrKhanna presented recommendations forannual screening of PAH in systemic scle-rosis patients at another session at themeeting (See article on page 8)

Although 4 of patients are still beingmissed this is a dramatic improvementover current clinical practice said DE-TECT investigator Dr Christopher Den-ton who presented the findings of theinternational multicenter trial The studywas also recently published online (AnnRheum Dis 2013 May 18 [doi101136annrheumdis-2013-203301])

ldquoThere is a general feeling that pa-tients need to be screened so that diag-noses can be made and licensedtherapies can be initiatedrdquo said Dr Den-ton of the Royal Free Hospital in Lon-don ldquoThe goal of the study was to

rationalize a large numberof potential variables intoa small number that couldbe developed into a riskscorerdquo he added and ldquoul-timately to ensure that themost appropriate patientsare referred for diagnosticright heart catheter stud-iesrdquo Right heart catheter-ization (RHC) remains theonly method for confirm-ing a diagnosis of PAH

A total of 646 adult pa-tients with established scleroderma(greater than 3 years) and reduced diffus-ing capacity of the lung for carbonmonoxide (DLCO less than 60 of pre-dicted) were screened and 466 enrolled inthe study All of them underwent RHCand 145 (31) were found to have PAHThis was defined as a mean pulmonaryarterial pressure of 25 mm Hg or high-er

Of the 145 patients with PAH 87 metWorld Health Organization (WHO)group 1 criteria for mild PAH and this wasthe group of interest as a diagnosis ofPAH ldquohad been robustly excludedrdquo bynormal methods Dr Denton said Thisgroup of patients was compared with thegroup that did not have PAH (n = 321)

Patients with WHO group 1 PAH wereslightly older than patients who did nothave PAH (mean ages 61 and 56 years)The PAH patients also tended to have alonger disease duration (163 vs 130months) and had slightly lower DLCO(43 vs 48 of predicted)

The DETECT investigators examined112 variables including demographic andclinical parameters serum tests and elec-tro- and echocardiogram results that theythought might be able to help differenti-ate patients with PAH from those withoutit After expert analysis and various typesof statistical modeling they ended upwith eight items that were used to devel-op the two-step algorithm

Step 1 of the algorithm involves testingfor lung function expressed as a ratio ofthe percentage predicted forced vital capac-ity and DLCO the presence of current or

DR CHRISTOPHER DENTON

Click here to view a video interview with Dr Dinesh Khannaabout the DETECT study

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MRI Detects High Level of SubclinicalSmall Joint Inflammation in Early Arthritis


Ahigh percentage of patients withearly arthritis have inflammation of

the small joints that can be detectedwith MRI but not by physical examina-tion

Results of a cross-sectional study pre-sented by Dr Annemarie Krabben at theCongress found that 66 of wrist 27of metacarpophalangeal (MCP) and13 of metatarsophalangeal (MTP)joints that were not clinically swollen

showed signs of inflammation on MRIHowever inflammation on MRI waspresent in 92 of wrists 86 of MCPand 29 of MTP joints that were clini-cally swollen

ldquoYou would expect that inflammationon MRI would be present in the clinical-ly swollen joints but we also saw inflam-mation in the nonswollen jointsrdquoexplained Dr Krabben of Leiden Univer-sity Medical Center in the Netherlands

Furthermore ldquowhen you look at thejoints with MRI-detected inflammation a

lot of thesedidnrsquot have clini-cal inflamma-tionrdquo she added

Clinical jointswelling was ab-sent but signs ofbone marrowedema was de-tected on MRIin 60 of wrist53 of MCPand 78 ofMTP joints Ifsevere MRI-de-tected edemawas consideredjoint swellingwas absent in35 39 and

58 of wrist MCP and MTP joints respec-tively Joints without clinical swellingshowed signs of inflammation on MRI in61 of wrist 64 of MCP and 77 ofMTP joints

The study involved patients with earlyarthritis who were part of the Leiden Ear-ly Arthritis Clinic cohort Overall patientshad undifferentiated arthritis (37)rheumatoid arthritis meeting the 2010American College of Rheumatology-Euro-pean League Against Rheumatism criteria(36) or other diagnoses (27) This co-hort was established in 1993 to detect andtreat inflammatory disorders early in thedisease state (Rheumatology [Oxford]20115093-100)

Upon entry into the cohort patientsunderwent a physical examination that in-cluded 68 tender and 66 swollen jointcounts and 15-Tesla MRI of the wristMCP and MTP joints The latter wereused to determine the presence and ex-tent of synovitis bone marrow edemaand tenosynovitis

In total 1790 small joints were exam-ined in 179 patients who had a median du-ration of symptoms of 15 weeks Overall30 of wrist 15 of MCP and 11 ofMTP joints were swollen at physical ex-amination and the majority also showedinflammation on MRI

Click here to listen to an audio interviewwith Dr Annemarie Krabben

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past telangiectasia serum anticentromereantibody positivity serum levels of N-ter-minal prohormone brain natriuretic pep-tide (NT-proBNP) serum urate levels andright axis deviation on an electrocardio-gram Step 2 involves measurement oftwo echocardiographic parameters rightatrium area and tricuspid regurgitationvelocity

ldquoThe aim is to make this a computer-based systemrdquo Dr Denton explained Atrial electronic version of the tool is be-ing tested which involves the aforemen-tioned clinical variables being enteredfirst to determine if an echocardiogramis warranted and then determining if theresults of the echocardiogram warrant

further referral for RHC The rates of referral for RHC were high-

er if the two-step algorithm was usedcompared with the use of ESCERS guide-linendashrecommended methods (62 and40) The specificity of the algorithm was48 with positive and negative predictivevalues of 35 and 98 respectively Thevalues for guideline-recommended meth-ods were 69 40 and 89

The DETECT algorithm has the poten-tial to revise standards of care in patientswith systemic sclerosis Dr Denton not-ed that not only was it a sensitive nonin-vasive screening tool but that it also hadthe potential to reduce the number ofmissed diagnoses and to potentially iden-tify PAH earlier in mildly symptomaticpatients

ldquoThe reason to use a two-step ap-proach is that this potentially will im-prove the use of echocardiography aswell as the more invasive test of rightheart catheterizationrdquo he commentedldquoSo we hope that this sort of approachwill ultimately improve the approachand the standard of care for systemicsclerosisrdquo

DETECT was an academic-led studyfunded by Actelion Dr Denton has re-ceived consulting and speaker fees andorresearch funding from or has been a clin-ical trial investigator for several compa-nies including Actelion BoehringerIngelheim and CSL Behring Dr Khannadisclosed acting as a consultant for sever-al companies including Actelion Bayerand Celgene




Rheumatoid Arthritis Remission Similar forTocilizumab Alone or With Methotrexate

B Y M I C H E L E G S U L L I VA N

Patients with early active rheumatoidarthritis who took tocilizumab ndash ei-

ther alone or in combination withmethotrexate ndash continued to benefit fromit by the end of a 2-year study

About half of those on either treatmentstrategy in the study achieved remissionby the end of the first year and this did notchange appreciably by the end of the sec-ond year There was also a very low rateof radiographic progression Dr TomHuizinga said at the Congress

The results confirm and extend theearlier findings of ACT-RAY a 2-yearrandomized placebo-controlled studyof tocilizumab employed as a switch oradd-on therapy for patients with earlyactive rheumatoid arthritis (RA) The 24-week data published earlier this yearshowed that tocilizumab was just as ef-fective without methotrexate as with itsuggesting that it could be employed asmonotherapy (Ann Rheum Dis20137243-50)

All 553 patients in ACT-RAY receivedopen-label tocilizumab 8 mgkg intra-venously every 4 weeks They were ran-domized to the switch strategy(tocilizumab 8 mgkg IV every 4 weekswith oral placebo) or the add-on strate-gy (tocilizumab 8 mgkg IV every 4weeks plus 25 mg methotrexate) saidDr Huizinga head of the department ofrheumatology at Leiden (the Nether-lands) University Medical Center

Most of the patients (81) werewomen mean age was 53 years Patientshad a mean disease duration of 8 years

and a mean Disease Activity Scorendash28(DAS28) of 64

Most of the study group (433) com-pleted the second year of treatmentReasons for withdrawal included lack ofefficacy (2 in the add-on strategygroup and 5 in the switch strategygroup) and adverse events (10 of add-on patients and 11 of switch) Therewere three deaths in the add-on groupand six in the switch group

Sustained remission was defined as aDAS28 of less than 26 at two consecutivevisits separated by 12 weeks By week 52about 50 of the overall cohort (53 add-on strategy and 47 switch strategy) hadachieved remission and were able to dis-continue tocilizumab

By week 104 86 of the overall cohort

had experienced a flare in disease activitywith a median time of 90 days fromtocilizumab discontinuation Most ofthose patients restarted tocilizumab Themedication continued to be effective Themean DAS28 at flare was 446 droppingto a mean of 299 within 4 weeks ofrestarting treatment

The mean DAS28 score at week 104was unchanged from the score at week 52decreasing by 36 from baseline in bothgroups The large majority of each groupexperienced no radiographic progressionduring year 2 (94 of the add-on and 91of the switch groups)

By the end of the study at week 10423 of the add-on group and 18 of theswitch group were in remission as meas-ured by the Clinical Disease Activity In-dex ndash virtually identical to CDAIremission rates at week 52

The safety results were consistent withprevious findings Dr Huizinga said Se-rious adverse events and infections oc-curred in 15 of the add-on group and4 of the switch group

Liver enzyme elevations were morecommon among those in the add-ongroup Elevations of up to three times theupper limit of normal of alanine amino-transferase occurred in 58 of the add-on group and 40 of the switch groupElevations of up to five times the upperlimit occurred in 13 of the add-on groupand 5 of the switch group Aspartatetransaminase elevations of up to threetimes the upper limit of normal occurredin 51 of the add-on group and 30 ofthe switch group Elevations of up to five

Dr Tom Huizinga The issue of clinicalimpact has not yet been addressed

MIC

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ldquoThere was a lot of subclinicalinflammation especially bonemarrow edema in thenonswollen jointsrdquo Dr Krabbensaid Bone marrow edema islinked to erosive disease pro-gression she observed and sug-gested that the next step is to seewhat happens to patients withsubclinical inflammation at

baseline and whether this willeventually progress to erosivedisease

The study was supported bythe Dutch Arthritis Foundation(Reumafonds) the NetherlandsOrganization for Health Re-search and Development andthe Center for Translational Mol-ecular Medicine Dr Krabben hasreceived research funding fromReumafonds


This MRI of the wristshows subclinicalinflammation in apatient with earlyarthritis symptomscopy

LE

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New Scoring Method Assesses Large-JointDamage in Treated Rheumatoid Arthritis


Anew radiographic scoring methodsuccessfully assessed damage in the

large joints of patients with rheuma-toid arthritis who were being treatedwith biologic therapy according to re-search presented at the Congress

The ARASHI (Assessment ofRheumatoid Arthritis by Scoring ofLarge-Joint Destruction and Healing inRadiographic Imaging) method devel-oped by a team in Japan was testedover a period of 2 years in 51 patientswho were being newly treated with tu-mor necrosis factorndashalpha (TNF-alpha)inhibitors

ldquoEvaluation of radiographic damageof the small joints in the hands and feetusing the van der Heijde total Sharp scorein patients with early RA [rheumatoidarthritis] has been establishedrdquo said DrIsao Matsushita assistant professor in theorthopedic surgery department at theUniversity of Toyama Japan

While the Larsen grade is most oftenused to assess large joints this ra-diographic grading system has severallimitations including a ldquoceiling effectrdquo re-sulting from the substantial variationfound within each of the six Larsengrades (scored 0-5) he said in an inter-view at the meeting Dr Matsushita andhis colleagues developed the ARASHImethod to offer a more sensitive meansof determining radiographic progressionin the large joints

The ARASHI method is composed oftwo parts (Mod Rheumatol 2013 April27 [doi 101007s10165-012-0823-6]) DrMatsushita explained First there is a sta-tus score which takes four categoriesinto account joint space narrowing(scored 0-3) erosion (scored 0-3) jointsurface (0-6) and joint stability (0-4)

Second there is a change score whichassesses the same four categories plusthe porosity of the joint

A total of 57 patients with early RAwho were about to be treated with TNF-alpha inhibitors were included in thestudy and 51 completed 2 yearsrsquo treat-ment with theseagents Themost frequentlyprescribed TNF-alpha inhibitorswere infliximabin 24 patientsand etanerceptused in 14 an-other 7 patientsswitched frominfliximab toetanercept and6 patients weretreated witha d a l i mu m a bThe mean ageof the patientswas 60 yearswith a mean RAduration of 106years

The investiga-tors used theARASHI statusscore to assess 96 hip and 86 knee jointsat baseline (before TNF-alpha inhibitortreatment was started) They later com-puted the ARASHI change score for thejoints at both 1-year and 2-year follow-upvisits A 1-point or more increase in theARASHI change score constituted ra-diographic progression Higher scores in-dicated higher levels of joint damage

All of the hip and knee joints with astatus score of greater than 2 showedprogression of joint damage under TNF-blocking therapies Dr Matsushita said

He added that of the joints with a lowbaseline ARASHI status score (0-2) only65 showed progressive damage overthe course of the study Furthermorethe joint-space narrowing score wasmore closely related to the joint damagesubsequently seen than was the erosion

scoreTaken together these findings demon-

strate that the ldquoARASHI scoring methodis useful for the evaluation of radiograph-ic damage in large weight-bearing jointsand to predict the risk for progression inpatients with RArdquo said Dr Matsushitanoting that the next step is to look at theutility of the score in other large jointsperhaps the shoulder elbow and anklejoints

Dr Matsushita said that he had no dis-closures

The new system avoids the ldquoceiling effectrdquo of the Larsengrading system Dr Isao Matsushita said

SA

RA

FR

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times the upper limit of normal occurredin 5 of the add-on and 2 of the switchgroups

During a discussion period after hispresentation Dr Huizinga addressed the

issue of clinical impact saying all of theinformation isnrsquot in yet Patients will befollowed for an additional year for struc-tural or joint damage

ldquoClinical meaningfulness is an intensediscussion that we will have to conductrdquo hesaid ldquoIrsquom not quite sure of it myself yetrdquo

The study was funded by F Hoffmann-La Roche Dr Huizinga disclosed that heis a consultant for Abbott Axis Shield Di-agnostics Biotest AG Bristol-MyersSquibb Crescendo Bioscience RocheNovartis Schering-Plough UCB Wyethand Pfizer



ONE BIOLOGIC MONOTHERAPY STANDS OUT1 in 3 RA patients receive biologic monotherapy1ndash7

RoACTEMRA is the only biologic proven superior to a TNF inhibitor (adalimumab) in RA monotherapy8

PRESCRIBING INFORMATION RoACTEMRAreg (tocilizumab) in Rheumatoid Arthritis (RA) Please refer to RoACTEMRA SPC for full prescribing informationIndication RoACTEMRA in combination with methotrexate (MTX) is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have either responded inadequately to or who were intolerant to previous therapy with one or more disease-modifying anti-rheumatic drugs (DMARDs) or tumour necrosis factor (TNF) antagonists In these patients RoACTEMRA can be given as monotherapy in case of intolerance to MTX or where continued treatment with MTX is inappropriate RoACTEMRA has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function when given in combination with MTX Dosage and Administration Patients should be given the Patient Alert Card 8mgkg iv infusion given once every 4 weeks Doses exceeding 800mg per infusion are not recommended Dose adjustments Dose reduction to 4mgkg or interruptions are recommended in the event of raised liver enzymes low absolute neutrophil count (ANC) or low platelet count RoACTEMRA should not be initiated in patients with ANaC count below 2x109LContraindications Hypersensitivity to any component of the product active severe infectionsPrecautions Infections Cases of serious and sometimes fatal infections have been reported interrupt therapy until controlled Caution in patients with recurringchronic infections or other conditions which may predispose to infection Tuberculosis (TB) Screen for

and treat latent TB prior to starting therapy There is a risk of false negative tuberculin skin and interferon-gamma TB blood test results

especially in patients who are severely ill or immunocompromised Patients should be instructed to seek medical advice if signs

symptoms of a tuberculosis infection occur during or after therapy with RoACTEMRA Hypersensitivity reactions

Serious hypersensitivity reactions have been reported and may be more severe and

potentially fatal in patients who have experienced hypersensitivity

reactions with previous infusions even if they have received premedication with steroids and antihistamines Appropriate treatment should be available for immediate use if anaphylaxis occurs If an anaphylactic reaction or other serious hypersensitivityserious infusion related reaction occurs permanently discontinue RoACTEMRA Hepatic diseaseimpairment Use with caution in patients with active hepatic diseaseimpairment Transaminase elevations Not recommended in patients with ALT or AST gt5xULN caution in patients with ALT or AST gt15xULN Haematological abnormalities Caution in patients with platelet count lt100x103microL Continued treatment not recommended in patients with ANC lt05 x 109L or platelet count lt50 x 103microL Lipid parameters If elevated follow local guidelines for managing hyperlipidaemia Vaccinations Live and live attenuated vaccines should not be given concurrently Combined with other biologic treatments Not recommended Viral reactivation Has been reported with biologics Diverticulitis Caution in patients with a history of intestinal ulceration or diverticulitis Patients with symptoms of complicated diverticulitis should be evaluated promptly Interactions Patients taking other medicines which are metabolised via CYP450 3A4 1A2 or 2C9 should be monitored as doses may need to be adjusted Pregnancy and Lactation Women should use contraception during and for 3 months after treatment A decision on whether to continuediscontinue breastfeeding on RoACTEMRA therapy should take into account relative benefits to mother and child Undesirable effects Prescribers should consult SPC for full details of ADRs Very common ADRs (gt110) URTI hypercholesterolaemia Common ADRs (gt1100 to lt110) cellulitis pneumonia oral herpes simplex herpes zoster abdominal pain mouth ulceration gastritis rash pruritus urticaria headache dizziness increased hepatic transaminases increased weight and increased total bilirubin hypertension leukopenia neutropenia peripheral oedema hypersensitivity reactions conjunctivitis cough dyspnoea Medically significant events Infections Opportunistic and serious infections have been reported some serious infections had a fatal outcome Impaired lung function may increase the risk of developing infections There have been post-marketing reports of interstitial lung disease some of which had a fatal outcome GI perforations Primarily

reported as complications of diverticulitis Infusion reactions Clinically significant hypersensitivity reactions requiring treatment discontinuation were reported and were generally observed during the 2nd ndash 5th infusions Fatal anaphylaxis has been reported Other Decreased neutrophil count decreased platelet count hepatic transaminase elevations lipid parameter increases very rare cases of pancytopenia Legal Category POM Presentations and Basic NHS Costs 80mg of tocilizumab in 4mL (20mgmL) 1 vial pound10240 200mg of tocilizumab in 10mL (20mgmL) 1 vial pound25600 400mg of tocilizumab in 20mL (20mgmL) 1 vial pound51200 Marketing Authorisation Numbers EU10849201 (80mg) EU10849203 (200mg) EU10849205 (400mg) Marketing Authorisation Holder Roche Registration Limited 6 Falcon Way Welwyn Garden City Herts AL7 1TWRoACTEMRA is a registered trade markDate of preparation February 2013 RCUKMEDI00022

REFERENCES1 Lee SJ et al J Rheumatol 2009 36(8) 1611ndash16172 Yazici Y et al Bull NYU Hosp Jt Dis 2008 66 77ndash853 Soliman MM et al Ann Rheum Dis 2011 70 583ndash5894 Heiberg MS et al Arthritis Rheum 2008 58 234ndash2405 Askling J et al Ann Rheum Dis 2007 66 1339ndash13446 Listing J et al Arthritis Res Ther 2006 8 R667 Mariette X et al Rheumatology 2011 50 222ndash2298 Gabay C et al Lancet 2013 381 1541ndash1550

Date of preparation September 2013 ndash Zinc code GLACTE13090014

WHEN COMBINATION IS NOT AN OPTIONWHEN COMBINATION IS NOT AN OPTION

reactions with previous infusions even if they have received premedication with steroids and antihistamines Appropriate treatment should be available for immediate use if anaphylaxis occurs If an anaphylactic reaction or other serious hypersensitivityserious infusion related reaction occurs permanently discontinue RoACTEMRA Hepatic diseaseimpairment Use with caution in patients with active hepatic diseaseimpairment Transaminase elevations Not recommended in patients with ALT or AST gt5xULN caution in patients with ALT or AST gt15xULN Haematological abnormalities Caution in patients with platelet count lt100x103microL Continued treatment not recommended in patients with ANC lt05 x 109L

If elevated follow local guidelines for managing hyperlipidaemia Vaccinations Live and live attenuated vaccines should not be given concurrently Combined with other biologic treatments Not recommended Viral reactivation Has been reported with biologics Diverticulitis Caution in patients with a history of intestinal ulceration or diverticulitis Patients with symptoms of complicated

Patients taking other medicines which are metabolised via CYP450 3A4 1A2 or 2C9

Pregnancy and Women should use contraception during and for 3 months after

treatment A decision on whether to continuediscontinue breastfeeding on RoACTEMRA therapy should take into account relative benefits to mother


REFERENCES1 Lee SJ et al J Rheumatol 2009 36(8) 1611ndash16172 Yazici Y et al Bull NYU Hosp Jt Dis 2008 66 77ndash853 Soliman MM et al Ann Rheum Dis 2011 70 583ndash5894 Heiberg MS et al Arthritis Rheum 2008 58 234ndash2405 Askling J et al Ann Rheum Dis 2007 66 1339ndash1344

20 14TH ANNUAL EUROPEAN CONGRESS OF RHEUMATOLOGY20 14TH ANNUAL EUROPEAN CONGRESS OF RHEUMATOLOGY

Ultrasound Speeds New RheumatoidArthritis Diagnoses and Treatment


Routine joint scans by ultrasound inpatients with suspected rheuma-toid arthritis led to faster diagnoses

and quicker initiation of disease-modify-ing treatment in a multicenter-study ofmore than 250 patients

But the results did not address whetherthis earlier diagnosis and treatment pro-duced better outcomes ldquoWhile earlier di-agnosis and treatment is known to lead tobetter outcomes a large prospectivestudy is required to explore the long-term clinical impact and cost-effectivenessof wider routine use of ultrasound byrheumatologistsrdquo Dr Stephen Kelly saidat the Congress

Despite this current limitation of theavailable evidence Dr Kelly is convincedof the value of routine ultrasound exam-inations for joint assessment in patientswith possible rheumatoid arthritis (RA)ldquoYou can see raging inflammation injoints that are not swollen or tenderrdquo hesaid in an interview The discrepancy be-tween clinical symptoms and the ultra-sound appearance can be ldquosurprisingrdquosaid Dr Kelly a rheumatologist at MileEnd Hospital in Barts Health NHS Trustin London

The current study involved observationof patients referred by primary care physi-cians to rheumatologists at four UK hos-pitals Each of the four sites selectedincluded some rheumatologists who rou-tinely used ultrasound and others whodid not

By the end of the study 134 patientshad been assessed with ultrasound jointexaminations and 124 had been assessedwithout ultrasound All patients were ini-tially seen in the referral rheumatologyclinics an average of 5 months after symp-tom onset They had a mean age of about53 years and about 70 were women

Among the 134 patients assessed initial-ly with ultrasound the average time to aformal RA diagnosis was 224 monthsand the median time was 089 monthsAmong the patients not examined withultrasound a formal RA diagnosis wasmade at a mean of 276 months and a me-dian of 2 months These differences werestatistically significant

The investigators eventually diag-nosed RA in 54 of the patients assessedwith ultrasound and in 58 patients as-sessed without ultrasound The mediantime to the start of treatment with a dis-

ease-modifying antirheumatic drug(DMARD) was 062 months among pa-tients routinely examined with ultra-sound and 141 months among those

V I E W O N T H E N E W S

Ultrasound Helps Early Diagnosis inChallenging Cases

The main issue when imaging joints inpatients with suspected rheumatoid

arthritis (RA) or early disease is Whatdoes imaging add to a standard clinical ex-amination Standard x-rays do not showmany erosions in patientswith early disease ultra-sound as well as MRI aremuch more sensitive Bothultrasound and MRI can bevery helpful for difficult-to-diagnose cases In my expe-rience about 5-10 ofearly-diagnosis cases bene-fit from using ultrasoundor MRI imaging of joints

Ultrasound is morewidely used than MRI is and also costsless You can examine multiple jointswith ultrasound you donrsquot need to injectcontrast and you can also use the ultra-sound to guide injections For all thesereasons ultrasound has rapidly becomewidely used to aid early diagnoses Butnot every clinician has the expertise toperform ultrasound examinations and ithas not yet been definitively proven thatusing ultrasound routinely for diagnosti-cally challenging cases is cost effective Isuspect it is cost effective to perform ul-trasound examinations fairly broadly onpatients suspected of having RA com-pared with the financial and social costsof delayed RA diagnosis in which the pa-tient goes untreated for an added periodof time but study results are still neededto prove this

In June I chaired a task force that is-sued the European League AgainstRheumatismrsquos first recommendations onusing joint imaging in the managementof RA (Ann Rheum Dis 201372804-

14) The 10 recommendations made bythe task force include several that supportand encourage the use of ultrasound orMRI for both the initial diagnosis of RAas well as subsequent management

However because evi-dence is currently lackingto fully document the fea-sibility cost and trainingrequired to use methodslike ultrasound in routinepractice our recommen-dations could not be un-qualified For example ourfirst recommendation saysldquoWhen there is diagnosticdoubt conventional radi-

ography ultrasound or MRI can be usedto improve the certainty of a diagnosisof RA above clinical criteria alonerdquo Thelevel of evidence for this recommenda-tion is level III which is not the highestlevel In addition note that the recom-mendation says ldquocan be usedrdquo ratherthan mandating the use of ultrasound oranother imaging method In the sameway our third recommendation saysldquoUltrasound and MRI are superior toclinical examination in the detection ofjoint inflammation these techniquesshould be considered for more accurateassessment of inflammationrdquo Again thelevel of evidence III precluded us fromsaying anything more definitive thanldquoshould be consideredrdquo

Philip G Conaghan MB PhD is aprofessor of musculoskeletal medicine atLeeds (England) University He said thathe is a speaker on behalf of or an advisorto Bristol-Myers Squibb Pfizer and RocheHe made these comments in an interview




examined without ultrasoundPut another way among the patients

eventually diagnosed with RA 67 werediagnosed within a month of initial refer-ral when their rheumatologists routine-ly used ultrasound compared with 37of the RA patients diagnosed within thefirst month when ultrasound wasnrsquotused

Initiation of DMARD treatment forthe subgroup eventually diagnosed withRA happened in the first month for 63of the patients routinely assessed by ul-trasound and in 32 of those worked-

up without ultrasoundIn a further analysis the rheumatolo-

gists who assessed 134 patients with ul-trasound were askedwhether their use of ultra-sound made a differenceFifty-three percent said thatthe first scan they obtainedwas instrumental in mak-ing their diagnosis and39 said that a subsequentultrasound exam was criti-cal in their diagnosticprocess

The researchers alsoasked the rheumatologists

who used ultrasound whether the ultra-sound results played an important rolein management decisions Thirty-eight

percent of the rheumatol-ogists said that the first ul-trasound scan theyobtained played an impor-tant role in their manage-ment decisions and 57said that a subsequent ul-trasound scan affectedmanagement

The study was sponsoredby AbbVie Dr Kelly saidthat he had no personal dis-closures


Biologics Reduced Sick Leave in RA PatientsB Y B I A N C A N O G R A DY

Biologics and improved strategies fortheir use have significantly reduced

the relatively high rate of sick leaveamong patients with rheumatoid arthri-tis but more efficient multiprofession-al intervention strategies are still neededto reduce its incidence Mathilda BjoumlrkPhD reported at the Congress

Dr Bjoumlrk of Joumlnkoumlping UniversitySweden conducted a subanalysis of theSwedish Early Rheumatoid Arthritis co-hort study (Swedish acronym ndash TIRA)The study included patients with earlyrheumatoid arthritis and was designedto calculate direct and indirect costs of

the disease over a 3-year period Therehave been two TIRA cohorts ndash one in1996-1998 and one in 2005-2008 All hadearly disease they were a mean of 62years at baseline

At all follow-up visits the patients metwith a multidisciplinary team including aphysician an occupational therapist anda physiotherapist and were given individ-ual treatment based on their needs

Those in the more recent cohort weretreated more aggressively with disease-modifying antirheumatic drugs(DMARDs) mainly methotrexate start-ing at their first visit They also receivedbiologics when required

Dr Bjoumlrkrsquos study examined sick leave

rates between the two TIRA cohorts1996-1998 and 2005-2008 The compari-son found that sick leave rates in the new-er cohort declined about 50 comparedto those in the older cohort

In the early cohort sick leave rateswere stable over the 3-year study periodAt baseline 60 of the patients weretaking sick leave due to their RA thatnumber was unchanged at 3 years

In the newer cohort the baseline sickleave rate was similar with 55 takingleave due to their disease But at the 3-year follow-up only 30 were on sickleave

ldquoI think itrsquos good newsrdquo Dr Bjoumlrk saidin an interview Since both groups weremaking use of the multidisciplinary teamtreatment DMARD treatment appearedto be the main driver behind the differ-ence ldquoThey are being used more fre-quently and in higher doses and itrsquosworkingrdquo

Dr Bjoumlrk said the study came about notonly because RA is associated with suchhigh indirect costs for sick leave but alsobecause of the direct treatment costs ofnew medications such as biologicalagents

ldquoThe rationale behind the study wasto explore whether more effective dis-ease control reduces sick leave in a post-biologic cohort compared to aprebiologic cohort with the potentialfor compensating some of the increasedtreatment costrdquo

The researchers suggested that changesin political policies and the sickness insur-

Click here to view video interview with Mathilda Bjoumlrk PhD

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DR STEPHEN KELLY




Earlier Biologic Use Is on the Rise in PatientsWith Juvenile Idiopathic Arthritis


Biologic agents are increasingly beingused in the treatment of juvenile id-

iopathic arthritis earlier in the course ofthe disease and in less severe cases accord-ing to longitudinal data from the DutchNational Arthritis and Biologicals in Chil-dren Register

Etanercept was the most commonlyused biologic in nonsystemic cases of JIAwhile anakinra was the most commonlyprescribed biologic agent for systemic dis-ease over a 12-year evaluation period

ldquoTreatment strategies in JIA havechanged over the past decade especiallysince the introduction of biologicsrdquo saidJanneke Anink a third-year postgraduatestudent at Erasmus MC-Sophia ChildrenrsquosHospital in Rotterdam the NetherlandsThis has been possible because of a bet-ter understanding of the immunologicand biologic mechanisms underlying theinflammatory joint disease

Etanercept which blocks tumornecrosis factor (TNF) was the first bio-logic agent to be registered in Hollandin 1999 Ms Anink noted Additionalanti-TNF therapies such as infliximaband adalimumab became available in2007-2008 followed by the interleukin(IL-1) blockers canakinumab and anakin-ra in 2009-2010 and more recently theIL-6 blocker tocilizumab in 2011

Alongside the availability of these nov-el drugs treatment goals have changedfrom the prevention of long-term jointdamage and disability to achieving inac-tive disease through more aggressiveand earlier therapy Ms Anink said at theCongress (Ann Rheum Dis201372154) Itrsquos not known howeverwhether the use of these drugs actually

leads to better patient outcomesMs Anink and her associates therefore

set out to determine how prescriptiontrends had changed in Holland since bi-ologic agents became available and howsuch trends might have influenced pa-tient outcomes The team used datafrom the Dutch National Arthritis andBiologicals in Children (ABC) Registerwhich is an ongoing multicenterprospective observational initiative thatbegan in 1999 with the aim of includingall patients with JIA who are treatedwith a biologic agent for their condition

Upon inclusion in the ABC Registerkey patient characteristics are collectedincluding age gender JIA category age atdiagnosis disease duration and priormedication use Patients are also assessedfor current medication use adverse eventsof treatment and a host of laboratory anddisease activity parameters which are as-sessed again 3 and 6 months after inclu-sion and then annually

A total of 429 cases were included in thecurrent analysis of which 343 patientshad nonsystemic and 86 had systemic dis-ease Patients had started treatment withat least one biologic agent between 1999and 2010 There were 82 prescriptions forbiologic agents in 2010 for both systemicand nonsystemic JIA compared with only12 during 1999-2000

Biologic agents were prescribed aftershorter disease durations in 2008-2010compared with 1999-2001 droppingfrom 53 years to 30 years respectivelyin nonsystemic JIA and from 35 years to04 years respectively for systemic dis-ease Ms Anink reported

Nonsystemic JIA patients with lowerdisease activity at baseline were also be-ing treated with these drugs Indeed

the median number of active joints atbaseline fell from 18 before biologictherapy was given to 5 The mediannumber of joints with limited motiondecreased from 12 to 3 and ChildhoodHealth Assessment Questionnaire(CHAQ) scores fell from 18 to 11 overthe same time periods

Importantly the proportion of pa-tients with inactive disease after 3months of therapy increased dramatical-ly from 0 in 1999-2001 to 34 during2008-2010 for nonsystemic disease andfrom 0 to 64 for systemic disease

ldquoWe saw the threshold for prescriptiondecreased which was earlier in the dis-ease course and in patients with lowerdisease activityrdquo Ms Anink summarizedldquoWith these trends we say the short-term treatment outcomes improved inall JIA categoriesrdquo

Similar findings were presented sepa-rately at the meeting by a German teamDr Kirsten Minden of the GermanRheumatism Research Centre Berlin andher associates reported that the use of tra-ditional and biologic disease-modifyingagents for the treatment of polyarticularJIA rose and occurred earlier over a 12-year period (Ann Rheum Dis201372731) Improved patient health sta-tus including functional capacity meas-ured by the CHAQ score disease activitymeasured by the 10-joint Juvenile Arthri-tis Disease Activity Score and pain andoverall well-being coincided with treat-ment changes

The ABC Register was financially sup-ported by the Dutch Board of Health In-surances (from 2003 to 2006) Pfizer(formerly Wyeth International since2007) and Abbott (since 2010) MsAnink had no disclosures to report

ance system may also have had some im-pact on the differences in sick leave be-tween the two cohorts

Despite the significant reductions insick leave she suggested that more couldbe done to address the persistently high

rate of sick leave among individuals withRA

ldquoThe impact of rheumatoid arthritison an individualrsquos ability to work is acomplex interaction of biological psy-chological social and occupational fac-torsrdquo she said ldquoThe interventions needto have a wider perspective than the

rheumatoid arthritis per se and [shouldbe] done in a close interaction betweenthe patient clinicians employers andpolicy makers early in the diseaseprocessrdquo

Dr Bjoumlrk had no conflicts of interestrelevant to the study




Coping Strategies Put OA Pain in CHECKB Y M I C H E L E G S U L L I VA N

Patients with knee osteoarthritis wholdquoretreatedrdquo into a passive copingstrategy and engaged in an unhealthy

lifestyle were likely to develop more long-term pain than were patients who stayedphysically healthy and emotionally strongin a large Dutch cohort study

ldquoTo diminish pain in patients with earlysymptomatic OA [osteoarthritis] attentionshould be given not only to pain com-plaints but also to effective use of copingstrategies and unhealthy lifestyle factorsrdquosaid the lead author of the study Janet Wes-seling PhD of University Medical CenterUtrecht the Netherlands ldquoThis is a furtherargument to take coping and lifestyle fac-tors into account in the management ofearly OArdquo

Her findings were extracted from data inthe CHECK (Cohort Hip and CohortKnee) study a 10-year prospective cohortstudy with a mirror cohort in the UnitedStates Itrsquos following 1002 patients with ear-ly OA-related complaints of hip andorknee pain (Ann Rheum Dis 201372[Sup-pl 3]152)

The studyrsquos pain trajectory subanalysisincluded 5-year data on 705 patients withsymptomatic knee OA Dr Wesselingidentified three trajectories in these pa-tients good moderate and poor painoutcomes

Patients with a good outcome trajecto-ry (n = 222) had over time a slight decreasein pain severity and ended up with a lowpain severity Those with a moderate out-come trajectory (n = 294) had a stablecourse of moderate pain over time Thepoor outcome trajectory group (n = 189)had an increase in pain severity over time

and ended up with severe pain Compared with the good-outcome

group participants in the other groupswere significantly more likely to have ahigher body mass index (odds ratio = 11)Patients in the moderate- and poor-out-come groups were significantly more like-ly to smoke than were those in thegood-outcome group(moderate outcomeOR = 18 poor out-come OR = 23) DrWesseling reported atthe Congress

There were signifi-cant differences in cop-ing strategies as wellThe poorer-outcomegroups were morelikely to have a passivecoping style Theywere significantlymore likely to worryabout their conditionthan was the good-out-come group (moder-ate outcome OR =23 poor outcome OR = 35) and morelikely to rest often (moderate outcome OR= 16 poor outcome OR = 24)

Over the long run there were also dis-ease-related physical differences Dr Wes-seling noted

After 5 years patients in the poor-out-come group experienced more joint de-struction and changes in osteophyte sizeshe said By that time 13 of patients inthe poor-outcome group had at least twograde changes on the Kellgren-LawrenceGrading Scale indicating more joint spacenarrowing osteophyte formation scle-rosis and bony contour deformity

Over time these patients also experi-enced significantly more osteophyte en-largement than did patients in themoderate- and good-outcome groups witha mean growth of 52 mm compared with34 mm and 29 mm respectively

Surgical outcomes were significantly dif-ferent in the poor-outcome group Dr Wes-

seling said Therewere 12 total knee re-placements in thepoor-outcome groupcompared with 4 inthe moderate-out-come group and just 1in the good-outcomegroup

Distinguishing dif-ferent trajectoriescould have implica-tions for treatmentDr Wesseling notedin an interview Clin-icians can suggest im-provements in theway patients chooseto deal with their con-

dition ndash beginning with an up-front con-versation

ldquoAt the very least the topic should bediscussed during counseling on OA Physi-cians should be alert to increasing stresslevels in their patients Sometimes physi-cians can help counsel patients aboutmanaging stress but a psychological con-sult might also be useful And self-man-agement programs can help patientsmanage and tolerate their painrdquo

The CHECK study is supported by theDutch Arthritis Association Dr Wessel-ing and her colleagues had no disclosuresto report

Janet Wesseling PhD Have an up-front talk about coping with pain



Symptomatic Hand Osteoarthritis Linkedto Increased Heart Disease Risk


Symptomatic hand osteoarthritis is as-sociated with a significant increase inthe risk of coronary heart disease

events although the association was notsignificant for asymptomatic hand os-teoarthritis according to results from astudy presented at the Congress

A population-based cohort study of 1348participants from the Framingham HeartStudy found more than double the inci-dence of coronary heart disease among in-dividuals with symptomatic hand OAcompared with those without hand OA(hazard ratio 226 95 confidence interval122-418) Dr Ida K Haugen reported

The study defined symptomatic handOA as one or more hand joints with Kell-gren-Lawrence grade of 2 or above andpain in the same joint The definition ex-cluded individuals with rheumatoid arthri-tis (RA)

The association persisted even after ad-justment for lower limb pain (HR 20095 CI 096-415) to account for the phys-ical inactivity potentially associated withOA in lower limb joints according to DrHaugen from Diakonhjemmet Hospital inOslo and her associates

However individuals with radiographicbut not symptomatic hand OA showed anonsignificant increase in the risk of coro-nary heart disease (HR 160 95 CI 096-266)

The study set out to examine a possibleassociation between hand OA and cardio-vascular disease based on the premisethat hand OA is especially likely to be re-lated to metabolic rather than mechanicalcauses

ldquoWe hypothesized that the associationbetween hand OA and coronary heart dis-ease could be mediated through metabol-

ic factors such as hyperlipidemia and dia-betes or a more sedate lifestyle due to gen-eralized OArdquo Dr Haugen said in aninterview

ldquoRadiographic hand OA is very prevalentin the general population and only a pro-portion of those with radiographic handOA may experience symptomsrdquo she saidldquoWe believe that symptomatic hand OArepresents more severe hand OA and fur-ther the association between hand OA andcoronary heart disease may be mediatedthrough factors associated with pain suchas synovitisrdquo

Synovitis has been shown in other dis-eases such as RA to increase the risk ofcardiovascular disease due to the develop-ment of atherosclerosis Dr Haugen said

The study failed to find any significant as-sociations between hand OA ndash either symp-

tomatic or radiographic only ndash and cardio-vascular events overall mortality heart fail-ure and atherothrombotic stroke

ldquo[W]e hypothesize that the varying asso-ciations may be due to different risk factorsfor coronary heart disease versus cere-brovascular disease and congestive heartfailure for example hypertension seems tobe more important for cerebrovascular dis-ease than for coronary heart diseaserdquo DrHaugen said

While further research is needed to ex-plore the mechanisms of the associationDr Haugen suggested that clinicians notethat patients with hand OA may be atgreater risk of coronary heart disease andpreventive strategies may therefore be ofgreater importance in this group

Dr Haugen reported having no relevantfinancial disclosures

Click here to view a video interview with Dr Ida K Haugen

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Ustekinumab Benefits in Psoriatic ArthritisPreserved Through 1 Year


The lessening of the signs andsymptoms of psoriatic arthritisthat occurs during the first 6

months of ustekinumab treatment per-sisted and improved further at the end of1 year with a favorable safety profile ac-cording to 52-week data from the PSUM-MIT II trial

The sustained benefits in AmericanCollege of Rheumatology (ACR) 20 re-sponses and other efficacy endpointswere evident even in patients who hadbeen treated previously with antindashtumornecrosis factor (anti-TNF) agents andamong those who were anti-TNF naivealthough the benefits were greater in thelatter group patients according to DrChristopher T Ritchlin a professor in thedepartment of medicine allergyim-munology and rheumatology at the Uni-versity of Rochester (NY) This includesbeneficial effects on skin and enthesitisDr Ritchlin said at the Congress

The PSUMMIT II study is a follow-up tothe PSUMMIT I study the findings ofwhich showed that ustekinumab a humaninterleukin (IL)-12 and IL-23 antagonistshowed significant effectiveness in patientswith psoriatic arthritis (PsA) who had notbeen exposed to anti-TNF drugs

Ustekinumab is currently approved for

treating moderate to severe plaque pso-riasis in adults who are candidates forphototherapy or systemic therapy in theUnited States or those who have failed torespond to have a contraindication to orare intolerant of other systemic therapiesin Europe In December 2012 the man-ufacturer Janssen announced that it hadfiled for further approval for ustekinum-ab in both the United States and Europefor the treatment of active disease

The PSUMMIT II study enrolled 312patients with active PsA who had five ormore tender and five or more swollenjoints and a C-reactive protein level of 03mgdL or higher Patients who had beentreated previously with anti-TNF therapy(n = 180) and those naive to anti-TNFtherapy (n = 132) were included and ran-domized to one of two doses of ustek-inumab (45 mg or 90 mg) or placeboadministered at week 0 4 and 12 At 16weeks patients with less than a 5 im-provement in tender and swollen jointcounts on placebo were switched to activetreatment those on 45 mg ustekinumabhad their dose upped to 90 mg and thoseon 90 mg remained on that dose

At 6 months significantly more pa-tients treated with ustekinumab thanplacebo achieved the primary endpointof an ACR 20 and more patients on ac-tive treatment had an ACR 50 and at

least a 75 improvement in the Psoria-sis Area and Severity Index (PASI 75)

These results were sustained at 1 yearwith 47-48 of those on 45 mg and 90mg and 56 of those who switched fromplacebo to the 45-mg dose achieving anACR 20 In addition 26-29 achievedan ACR 50 (29 for those switched fromplacebo) and 13-18 achieved an ACR

70 (15 for placebo)There were also improvements associ-

ated with treatment in HAQ-DI (HealthAssessment Questionnaire-Disability In-dex) scores at week 52 according to DrRitchlin The mean change in HAQ-DIscores from baseline to week 52 werendash021 for placebo ndash020 for the 45-mgdose of ustekinumab and ndash028 for the90-mg dose

Among those who had not been treat-ed before with an anti-TNF agent 59-60 of those on ustekinumab (73 forthose switched from placebo) achievedan ACR 20 at week 52 compared with37-41 of those who had taken ananti-TNF agent previously before beingtreated with ustekinumab (30 forplacebo) Although responses amonganti-TNF naive patients were superiorthe responses among those who hadbeen treated with these agents previous-ly were still significantly improved an in-dication that ustekinumab ldquooffers analternative for patients who cannot take


Dr Christopher T Ritchlin

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Click here to view a video interview with Dr Arthur Kavanaughabout the PSUMMIT II trial

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or fail anti-TNF agentsrdquo Dr Ritchlinsaid in an interview

Treatment was ldquovery effectiverdquo forskin symptoms and for enthesitis henoted Compared with baseline dactyli-tis was improved by a median of 95among those on the 45-mg dose 91among those on the 90-mg dose and100 in those who switched from place-bo to the 45-mg dose of ustekinumabSimilar improvements in enthesitis wereseen with the highest improvement(60) seen with the highest dose ofustekinumab PASI scores at baselineranged from 11 to 13 and improved by

56-64 by follow-up at week 52In general ustekinumab was well tol-

erated with no deaths or cases of tuber-culosis reported and with similar rates ofadverse events and serious adverseevents between the two doses ( just un-der 6) There were two malignanciesone breast cancer and one squamous cellcarcinoma in two patients taking the 90-mg dose of ustekinumab who had bothbeen treated with anti-TNFs previouslyThe rate of serious infections was lessthan 1 among those treated withustekinumab Through 60 weeks oftreatment there were three major ad-verse cardiovascular events all myocar-dial infarctions in patients treated with

ustekinumab These patients all hadmultiple cardiovascular risk factors DrRitchlin said They had also been ex-posed previously to anti-TNF treatment

Radiographic data from the trial are ex-pected and likely to be available by theend of the year for presentation at the an-nual American College of Rheumatologymeeting

Dr Ritchlin disclosed having receivedgrant and research support fromJanssen Four of the nine remaining au-thors are Janssen employees and share-holders of Johnson amp Johnson Janssenrsquosparent company

Sara Freeman contributed to this report


Effects of Apremilast Sustained at 1 Year inPsoriatic Arthritis Patients


Apremilast improves the signs andsymptoms of psoriatic arthritis in

about 60 of patients at 1 year accord-ing to long-term data from the PALACE1 trial

At week 52 a 20 improvement in dis-ease symptoms according to AmericanCollege of Rheumatology (ACR 20) re-sponse criteria was achieved by 57-63of patients treated with apremilast pro-viding evidence of sustained treatment ef-fects

The PALACE 1 trialrsquos primary end-point of an ACR 20 at 16 weeks alreadyreported last year was achieved by 31of patients treated with apremilast 20mg and 40 of those given apremilast30 mg compared with 19 of those giv-en placebo

ldquoOral apremilast demonstrated long-term efficacy including improvement insigns and symptoms and physical func-tion and skin manifestationsrdquo Dr ArthurKavanaugh professor of medicine at theUniversity of California San Diego saidat the Congress

Apremilast is an oral phosphodiesterase4 inhibitor under investigation as a treat-ment for active psoriatic arthritis (PsA) Itis being evaluated as a possible treatmentfor skin psoriasis ankylosing spondylitisrheumatoid arthritis and Behccediletrsquos dis-ease

PALACE 1 was a phase III multicenterdouble-blind placebo-controlled study ofapremilast for the treatment of activePsA A total of 504 patients with a docu-mented diagnosis of PsA for at least 6months were recruited into the study(Ann Rheum Dis 201372[Suppl 3]163)

Functional outcomes improvedPhysical function improved according to

measurements on the Health AssessmentQuestionnairendashDisability Index (HAQ-DI)

At baseline HAQ-DI scores were 121and ldquowe saw that patients improved byndash035 which is certainly the level that pa-tients can say lsquoI feel better and I can do mydaily activities betterrsquo rdquo Dr Kavanaughsaid

Click here to view a video interview with Dr Arthur Kavanaughabout the PALACE 1 and 3 trials

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Additionally 25 and 37 of patientstreated with apremilast 20 mg and 30mg respectively achieved a 75 improve-ment in the Psoriasis Area and Severity In-dex at 52 weeks which is a ldquovery highbarrdquo to achieve he noted

The main side effect seen was diar-rhea affecting 11-19 of patients giv-en apremilast and 24 given placeboHowever diarrhea occurred mainly inthe first 6 months of therapy and couldbe managed by taking appropriate meas-ures on an individual patient basis DrKavanaugh said This might include pre-scription of an antidiarrheal agent

ldquoProlonged exposure to apremilast didnot result in any unexpected increased in-cidence of adverse events or laboratoryabnormalitiesrdquo he noted The latter couldmean that if approved apremilast mightnot need routine laboratory monitoring

The PALACE development programPALACE 1 is one of several clinical trialsthat have investigated the efficacy andsafety of apremilast in active PsA Inthese studies 24 weeksrsquo treatment withone of two oral doses (20 mg or 30 mgtwice daily) of apremilast was comparedto placebo The primary endpoint of thestudies was the percentage of patientsachieving ACR 20 at 16 weeks

The trialrsquos inclusion criteria required pa-tients to have active disease despite priortherapy with disease-modifying an-tirheumatic drugs (DMARDs) biologic

agents or both Dr Kavanaugh notedthat the majority of patients had failedDMARD therapy in PALACE 1 with al-most one-quarter receiving prior biolog-ic therapy

Patients who had a less than 20 reduc-tion from baseline in swollentender jointcounts at 16 weeks were re-randomizedto receive apremilast 20 mg or 30 mg ifthey had originally been treated withplacebo while patients originally ran-domized to active treatment stayed ontheir initial dose if they failed to respondsignificantly At the end of the planned 24-week treatment period all remaining pa-tients on placebo were re-randomized toapremilast 20 mg or 30 mg until 1 year offollow-up

PALACE 3 data also reportedThe results of PALACE 3 and combined6-month safety data from the PALACE 1PALACE 2 and PALACE 3 trials were alsoreported at the Congress

In PALACE 3 (Ann Rheum Dis201372[Suppl 3]685) significantlymore patients achieved the primary end-point of an ACR 20 at 16 weeks if theywere treated with either the 20-mg dose(294 P = 02) or 30-mg dose (428P less than 0001) of apremilast com-pared with those given placebo (189)There was also statistically significantand ldquoclinically meaningfulrdquo improve-ment in physical function and pain ldquoTheresults of PALACE 3 support the effica-cy and safety findings of the PALACE 1study and help establish the profile of

apremilast in PsArdquo the PALACE 3 inves-tigators concluded

The pooled safety findings revealed nonew safety concerns and showed apremi-last was generally well tolerated (AnnRheum Dis 201372[Suppl 3]85) Ratesof diarrhea at 24 weeks were 126 and165 for the 20-mg and 30-mg doses ofapremilast and 28 for placebo respec-tively Other side effects of note includednausea (10 and 161 vs 46)headache (84 and 115 vs 46) andupper respiratory tract infection (7 and6 vs 3)

Time for regulatory approvalBased on the positive findings of thePALACE 1 2 and 3 studies apremilastrsquosdeveloper Celgene is expected to filefor regulatory approval in the treatmentof active PsA In doing so apremilastwill join another novel agent ustek-inumab in the queue for approval forthis indication

Ustekinumab is a human interleukin-12 and -23 antagonist produced byJanssen that is already approved in Eu-rope and in the United States for skinpsoriasis One-year data also show thatit is effective and well tolerated for PsAIt is given subcutaneously whereasapremilast is an oral agent

Dr Kavanaugh has provided expert ad-vice to andor received research grantsfrom the following companies Astra- Zeneca Bristol-Myers Squibb CelgeneCentocor-Janssen Pfizer Roche andUCB


New Spondyloarthritis Index Measures Patient-Relevant Outcomes


An international team has developed anew composite health index specifical-

ly for use in patients with ankylosingspondylitis

The Assessment of SpondyloArthritisInternational Society Health Index(ASAS HI) is based on the ICF (Interna-tional Classification of Functioning Dis-ability and Health) and includes 17dichotomous items that ask about pa-tientsrsquo levels of pain emotional func-tioning sleep habits sexual function

mobility self-care life in the communi-ty and employment The ICF is a com-prehensive and already well-recognizedand validated means of classifying anddescribing functioning disability andhealth in a systematic way

The tool has yet to be ldquofield testedrdquo tosee if it can measure changes in healthstatus in response to treatment Dr UtaKiltz said at the Congress where shewon a clinical science abstract award forher research

Dr Kiltz of Rheumazentrum Ruhrge-biet Herne Germany noted that the de-

velopment of the tool involved five keystages These have been outlined previ-ously (Rheumatology 201150894-8)and included a preparatory stage inwhich potential items for inclusion wereidentified Dr Kiltz and her colleaguesconsidered a total of 251 items obtainedfrom more than 60 existing question-naires such as the Bath AnkylosingSpondylitis Functional Index theDougados Functional Index and the ASQuality of Life Questionnaire

The investigators then conducted anContinued on following page



Exercise Program Improved Strength andWalking for Ankylosing Spondylitis Patients


Patients with ankylosing spondylitiswho participated in a progressive

muscle strengthening program gainedsignificant improvements in musclestrength and walking performance after4 months compared with those who didnot participate Dr Fabio Jennings re-ported at the Congress

The exercise program which involvedresistance training with the Swiss ballwas also well tolerated and was not as-sociated with negative effects on diseaseactivity said Dr Jennings of the rheuma-tology division at the Federal Universi-ty of Sao Paulo Brazil

Dr Jennings and his colleagues per-formed a randomized controlled single-blind prospective trial of 60 patientswith ankylosing spondylitis (AS)

Exercise is recommended for peoplewith AS but the benefits of a specific ex-ercise program have not been well de-fined Dr Jennings noted

In the study 30 patients were ran-domized to the supervised exercise pro-gram which entailed eight resistanceexercises using free weights on a Swissball twice a week for 16 weeks with in-creases in load every 4 weeks The 30 pa-tients in the control group continuedregular treatment with medicationswith no exercise Demographics clinicalfeatures and medications were similar inthe two groups at baseline

The impact of the exercise on func-

tional capacity quality oflife muscle strength andmobility was evaluated us-ing the BASFI (Bath Anky-losing SpondylitisFunctional Index) HAQ-S(Health Assessment Ques-tionnaire for Spondy-loarthropathies) the6-minute walk test andother assessment toolsevery 4 weeks Disease ac-tivity was measured withthe BASDAI (Bath Anky-losing Spondylitis DiseaseActivity Index) erythro-cyte sedimentation rate(ESR) and C-reactive pro-tein levels

After 4 months therewere statistically signifi-cant differences betweenthe two groups in thestrengths of the musclesused in performing the ex-ercises (abdominal squattriceps reverse fly androwing exercises) favoringthe intervention groupThese patients also hadsignificant improvementsin the 6-minute walk testand they were satisfiedwith the treatment as re-flected by significant differences be-tween the two groups in the Likert scaleused to assess patient satisfaction at all

time points measured In addition disease activity ndash as meas-

Use of a Swiss ball to perform the exercise program wasldquobeneficial and saferdquo Marcelo Cardoso de Souza said

CO

UR

TS

EY

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international cross-sec-tional study involving1915 patients with AS(mean age 51 years) Inthis second phase theysent a postal survey to pa-tients to ask about variousparameters An expertcommittee then assessedthe results in the thirdphase and selected 50items for possible inclusionin the final model The

penultimate stage in the developmentprocess involved sending a second postal

survey to 628 patientswith AS (mean age 485years)

In the final stage an ex-pert consensus meeting washeld where the final 17-itemtool was agreed upon (AnnRheum Dis 201372124)

ldquoASAS HI is a new com-posite index that capturesrelevant information onthe health status of pa-tients with ASrdquo Dr Kiltz

said ldquoIt is the first disease-specific indexwhich is based on the ICF and the itemsrepresent a whole range of abilities asdefined by the ICFrdquo

ASAS HI could eventually be used inclinical trials and clinical practice as anew composite index that captures rel-evant information on the health status ofpatients Dr Kiltz suggested

ldquoWe are now doing a field test to testthe 17 items in a wider range of pa-tientsrdquo she said After this is completedthe specifics of the tool will be pub-lished

Dr Kiltz had no conflicts of interest DR UTA KILTZ




ured by BASDAI ESR and C-reactiveprotein ndash did not worsen among thosewho participated in the exercise pro-gram

The study showed that this type of ex-ercise program using a Swiss ball to im-prove muscle strength ldquois a beneficial andsafe interventionrdquo in people with AS leadauthor Marcelo Cardoso de Souza a phys-iotherapist and member of a multidiscipli-nary rehabilitation team at the universitysaid in an interview

For these patients improvement inmuscular performance and functional ca-pacity is important Mr de Souza saidnoting that before clinicians refer patientsto such a program patients should under-go a medical evaluation and the programshould be provided by an experiencedprofessional

None of the investigators had relevantfinancial conflicts of interest

Evidence Grows for Use of TNF Inhibitorsin Axial Spondyloarthritis


Tumor necrosis factor inhibitors arefurther solidifying their position as

the go-to drug class for patients withspondyloarthritis who fail to adequatelyrespond to treatment with nonsteroidalanti-inflammatory drugs

Results from a series of reportsat the Congress gave further sup-port for the safety and efficacy oftumor necrosis factor (TNF) in-hibitors for treating axial spondy-loarthritis (SpA) and anotherreport at the meeting providedsome of the first evidence for effi-cacy of the TNF inhibitor class inpatients with the less-studied vari-ant peripheral SpA

TNF inhibitors ldquowork well forsymptoms and are the gold stan-dard for treating active axial SpArdquo said DrPhilip J Mease a rheumatologist atSwedish Medical Center in Seattle He re-ported evidence for the efficacy of a TNFinhibitor in patients with peripheral SpAwithout psoriatic involvement a form ofSpA that he said is increasingly being di-agnosed after it was first defined a fewyears ago The study that Dr Mease re-

ported on was the first to use the diagnos-tic criteria for peripheral SpA published bythe Assessment of Spondyloarthritis(ASAS) in 2011 (Ann Rheum Dis 20117025-31)

The ABILITY-2 (Study of Adalimumabin Subjects With Peripheral Spondy-

loarthritis) study enrolled patients in theUnited States Canada and several Euro-pean countries Patients either had an in-adequate response to at least two differentnonsteroidal anti-inflammatory drugs(NSAIDs) or were intolerant of or hadcontraindications for these drugs Studyparticipants received either 40 mg of adal-imumab (Humira) subcutaneously every

other week or placebo for 12 weeksThe studyrsquos primary endpoint was the

percentage of patients achieving the pe-ripheral SpA response criteria 40 at 12weeks a composite endpoint that requiresat least a 40 improvement on each ofthree measures patient global assessment

of disease activity patient global as-sessment of disease pain andswollen and tender joint count en-thesitis count or dactylitis count

The rate of patients fulfilling theprimary endpoint was 39 in 84 pa-tients treated with adalimumab and20 in 81 patients on placebo a sig-nificant difference Treatment withadalimumab also was linked to ldquosub-stantialrdquo and statistically significantimprovements after 12 weeks inphysical function health-relatedquality of life and work productiv-

ity Dr Mease reportedReports on using TNF inhibitors to

treat axial SpA at the congress includedresults from the first randomized con-trolled phase III trial of a TNF inhibitorto enroll patients from the full range ofaxial SpA including roughly equal num-bers of patients with ankylosing

DR PHILIP J MEASE DR JOACHIM SIEPER


Click here to view a video interview with Dr Fabio Jennings

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spondylitis and patients diagnosed withaxial SpA but without radiographicchanges The phase III RAPID-axSpA(Multicenter Randomized Double-Blind Placebo-Controlled Study to Eval-uate Efficacy and Safety of CertolizumabPegol in Subjects with Active AxialSpondyloarthritis) trial included 325 pa-tients enrolled at 104 sites in the UnitedStates and several other countries Thestudy enrolled patients who had an ele-vated blood level of C-reactive proteinevidence of sacroiliitis on an MRI scanor both and had failed to adequately re-spond to treatment with at least oneNSAID

Researchers randomized patients toreceive either 200 mg of certolizumabpegol subcutaneously every 2 weeks400 mg of certolizumab pegol subcuta-neously every 4 weeks or placebo Allpatients randomized to receive cer-tolizumab pegol began with three sub-cutaneous loading doses of 400 mgadministered at the studyrsquos start and af-ter 2 and 4 weeks Currently certolizum-ab pegol has no labeling for treatingpatients with axial SpA unlike severalother TNF inhibitors such as adalimum-ab and etanercept

The studyrsquos primary endpoint was thepercentage of patients achieving anASAS 20 response after 12 weeks oftreatment which requires at least a 20improvement in at least three of thesefour criteria patient global assessmentspinal pain assessment function and in-flammation This endpoint was reachedby 38 of the 107 placebo patients 58of the 111 patients who received cer-tolizumab pegol every 2 weeks and 64of those who received certolizumab pe-gol every 4 weeks showing statisticallysignificant differences in favor of the ac-tive treatment reported Dr Robert BM

Landeweacute at the CongressResponse rates were similar among

the patients with ankylosing spondylitisand those with no radiographic pathol-ogy After 24 weeks of treatment therate of ASAS 20 responders fell to 29of the placebo patients compared withincreases to 67 of patients receivingcertolizumab pegol every 2 weeks and to70 in those getting the drug every 4weeks

Dr Landeweacute who is a professor ofrheumatology at the Academic MedicalCenter in Amsterdam also presented re-sults for several other secondary meas-ures of response One of these theAnkylosing Spondylitis Disease ActivityScore (ASDAS) showed that inactivedisease developed after 24 weeks oftreatment in 4 of the placebo-treatedpatients 30 of the patients who re-ceived certolizumab pegol every 2weeks and 31 of patients who re-ceived the drug every 4 weeks The re-sults also showed no new signals ofadverse effects compared with severalprior pivotal trials of certolizumab pe-gol

Another set of measures in the samestudy focused on the impact of 24 weeksof treatment on work and householdproductivity and participation in socialactivities Among the 69 of patients inthe study who were employed treat-ment with either dosage of certolizum-ab pegol was associated with an averageof 10 more productive days of paid workper patient compared with placebo re-ported Dr Deacutesireacutee van der Heijde pro-fessor of rheumatology at LeidenUniversity in the Netherlands Duringthe 24 weeks of treatment the activeregimens also resulted in an added 13-17days of productive household work andan average of about 10 added days of so-cial or leisure activities compared withplacebo-treated patients

Results from a third study reported atthe meeting included outcomes from pa-tients with axial SpA and objective evi-dence of inflammation at entry whoremained on treatment with adalimum-ab during 2 years of follow-up in theABILITY-1 study This trialrsquos primary-endpoint results which were recentlypublished (Ann Rheum Dis 201372815-22) showed that 40 mg of adali-mumab administered every other weekwas significantly better than placebo forreducing disease activity after 12 weeksof treatment The new results camefrom 107 patients who remained in thestudy and received 104 weeks of adali-mumab treatment

After 2 years 66 of patients showedASAS 40 responses and 44 had inac-tive disease based on their ASDAS re-ported Dr Joachim Sieper professor andchief of rheumatology at Chariteacute Uni-versity Hospital in Berlin Most of thepatients in remission at 104 weeks hadalso been in remission after 52 and 80weeks of treatment In addition the 2-year data showed no new safety con-cerns compared with several other priorreports of long-term treatment withadalimumab he said

The ABILITY-1 and ABILITY-2 trialswere sponsored by AbbVie which mar-kets adalimumab Dr Mease has been aconsultant to and has received researchsupport from AbbVie and other compa-nies Dr Sieper has been a consultant toand has received research support fromAbbott (from which AbbVie was created)as well as Merck Pfizer and UCB TheRAPID axSpA trial was sponsored byUCB which markets certolizumab DrLandeweacute has been a consultant to and hasreceived research support from UCB andother companies Dr van der Heijde hasbeen a consultant to and has receivedgrant support from UCB and other com-panies


Panel Sets Broad SpA Treat-to-Target GoalsB Y M I T C H E L L Z O L E R

Apanel of clinicians with expertise inthe management of patients with

spondyloarthritis took another step to-ward better defining this disease catego-ry and the goals of its treatment byproducing the first ldquotreat-to-targetrdquo rec-

ommendations for spondyloarthritisThe new recommendations will

ldquoguide physicians patients and otherstakeholders on how to optimize reduc-tion of signs and symptoms and ideal-ly outcomes and will driverdquo the currentresearch agenda Dr Josef S Smolensaid while presenting the panelrsquos recom-

mendations at the CongressldquoTreat to target proposes a stepwise ap-

proach to achieving optimal outcomesbased on available evidence and expertopinion Treat to target has been success-fully applied to management of diabeteshypertension hyperlipidemia and




rheumatoid arthritisrdquo and the new taskforce set out to address whether it couldbe used when treating patients withspondyloarthritis (SpA) a question thatrequired the expert task force to reviewthe evidence for setting specific treat-ment goals for patients with SpA saidDr Smolen professor of medicine at theMedical University of Vienna

The task force eventually decided thatthe treat-to-target concept was applica-ble to SpA but that the data available sofar prevented the task force from settingspecific treatment goals While the rec-ommendations underscore the impor-tance of treating SpA patients with agoal of remission or inactive disease andfailing that at least low disease activitythey fall short of giving clinicians guid-ance on how to best measure and defineremission or low disease activity or howto achieve these goals

For example for axial SpA ndash the sub-type that received the most specific rec-ommendations ndash the panel advisedclinicians to guide treatment decisionsby using a ldquovalidated composite meas-ure of disease activityrdquo such as the BathAnkylosing Spondylitis Disease ActivityIndex (BASDAI) plus acute phase reac-tants or the Ankylosing Spondylitis Dis-ease Activity Score (ASDAS) with orwithout functional measures such asthe Bath Ankylosing Spondylitis Func-tional Index (BASFI) But the recom-mendations say nothing about whatscores by these measures would defineremission or low disease activity Therecommendations also talk about usingother factors to further gauge axial SpAdisease activity such as MRI analysis ofinflammation and radiographic progres-sion but again Dr Smolen provided nospecific targets when using these meas-ures

For other less well studied types ofSpA the new recommendations wereeven more nebulous For psoriatic arthri-tis the panel indicated that ldquovalidatedmeasures of musculoskeletal disease ac-tivityrdquo should be ldquoperformed and docu-mented regularlyrdquo as should otherfactors such as spinal and extraarticularmanifestations imaging findings andcomorbidities but the recommenda-tions gave no specifics on what any ofthese measures might be or what levelmight equal remission or low disease

The same held true for peripheral SpAOther factors touched on by the new

recommendations include the need forindividualized and shared decision mak-ing between physicians and patients theneed for coordination of care amongrheumatologists and other medical spe-cialists who treat SpA patients (derma-tologists gastroenterologists andophthalmologists) and the need to takeinto account extraarticular manifesta-tions of SpA diseases comorbiditiesand treat-ment risksalong withthe goal oflow diseaseactivity

ldquoI think itwas impor-tant to doc-ument thatthere is apaucity oftrials thathave lookedat strategies to treatrdquo SpA ldquoFor rheuma-toid arthritis we have strategies but notin spondyloarthritis and I think it is im-portant to say thatrdquo said Dr JuumlrgenBraun medical director of Rheumazen-trum Ruhrgebiet in Herne Germany

SpA also lags behind rheumatoidarthritis by not having any treatmentsproven to slow radiographic progres-sion ldquoAlthough we say that it is presum-ably important to treat inflammation[in patients with SpA] we are not surerdquosaid Dr Braun who served as a memberof the treat-to-target task force

Even though the task forcersquos reporthighlights the absence of evidence formost facets of SpA management ldquoin theabsence of evidence you need eminenceand thatrsquos what was producedrdquo DrBraun predicted that rheumatologistsand other clinicians who care for pa-tients with SpA would welcome thesenew recommendations despite theirshortcomings ldquoWhat we say is whatclinicians feel If a patientrsquos CRP is ele-vated we must do something about itbut the evidence supporting this is lim-ited Presumably it is important to treatinflammation but we are not yet surerdquohe said in an interview

ldquoWe donrsquot have trial results yet whereyou set up a quantifiable endpoint asyour target but that is comingrdquo said DrPhilip J Mease director of the rheuma-

tology clinical research division atSwedish Medical Center in Seattle and amember of the task force For examplethe results from the Tight Control ofPsoriatic Arthritis (TICOPA) trial ldquowilltell us whether more aggressive treat-ment to a quantifiable target is appropri-ate and makes a difference Weanticipate that it will but evidence iscurrently lackingrdquo The primary end-point of the TICOPA trial is change inthe ACR20 response but the trial in-

cludes sever-al otherc l i n i c a lmeasures ass e c o n d a r yendpoints i n c l u d i n gthe Assess-ment inAnkylosingSpondylitis(ASAS) theB A S D A I and the pso-

riasis area severity index (PASI) ldquoThe rheumatoid model is prompting

us to develop quantifiable measures likethe ASDAS and the new PsoriaticArthritis Disease Activity Score (PAS-DAS) that wersquoll start to see used I justspoke with a colleague about the needto also develop a similar measure for pe-ripheral SpArdquo Dr Mease said in an in-terview

The task force that developed thetreat-to-target recommendations includ-ed 16 physicians and patients on its steer-ing committee and 16 on an advisorycommittee The majority came fromvarious European locations but about aquarter of the task force members werefrom the United States To arrive at itsrecommendations the task force used acomprehensive literature review thatidentified 22 published reports that ad-dressed treatment targets for SpA (AnnRheum Dis 2013 June 10 [doi101136annrheumdis-2013-203860])The treat-to-target recommendationswere published online a few days beforeDr Smolenrsquos presentation at the meet-ing (Ann Rheum Dis 2013 June 8[do i 10 1136annrheumdis -2013 -203419])

Dr Smolen Dr Braun and Dr Measesaid that they had no disclosures relevantto the topic

DR JOSEF S SMOLEN DR JUumlRGEN BRAUN




Serum Biomarker Predicts RadiographicProgression in Spondyloarthritis


Elevated serum levels of vascularendothelial growth factor may bepredictive of radiographic pro-

gression in the spine according to datafrom a German study of patients withspondyloarthritis

The cutoff point appears to be at 600pgmL with the effects particularlystrong in patients who also develop syn-desmophytes which are bony growthsthat develop within ligaments

ldquoIn patients with syndesmophytesVEGF [vascular endothelial growth fac-tor] as a predictor of radiographic pro-gression performed better than CRP

[C-reactive protein]rdquo reported Dr DenisPoddubnyy at the Congress (AnnRheum Dis 201372125)

ldquoWe all know that radiographic pro-gression varies substantially among pa-tients with spondyloarthritisrdquo DrPoddubnyy observed ldquoUntil recentlythere was only one strong predictor ofradiographic progression the presenceof syndesmophytes at baselinerdquo headded

Last year however Dr Poddubnyy ofChariteacute Universitaumltsmedizin Berlin andhis associates published the findings of astudy involving 210 patients with earlyaxial spondyloarthritis (ax- SpA) who were recruited from the Ger-man Spondyloarthritis Inception Cohort(GESPIC) This study looked at baselinepredictors of spinal radiographic pro-

gression over 2 years and found that inaddition to radiographic damage elevat-ed CRP levels and cigarette smokingwere independently predictive (ArthritisRheum 2012641388-98)

The teamrsquos research also suggestedthat there could be a few serum bio-markers including VEGFthat could be predictiveso the investigators con-ducted a larger study in172 patients with definite(n = 95) or nonradi-ographic (n = 77) axSpA tolook specifically at the pos-sible association

Radiographs of thespine taken at baseline andat 2 yearsrsquo follow-up werereviewed independently bytwo readers who used themodified Stoke Ankylosing SpondylitisSpinal Score (mSASSS) to record the ex-tent of radiographic progression Ifthere was a worsening of 2 units ormore in mSASSS and the formation ofnew or increased growth of syndesmo-phytes radiographic progression hadoccurred

In total 22 patients had radiographicprogression including 18 with new for-mation or growth of syndesmophytes

Baseline VEGF was measured in theserum at baseline and was significantlyhigher in patients who developed radiographic progression at 2 years than inthose who did not (562 plus or minus357 pgmL vs 402 plus or minus 309pgmL P = 027)

Serum VEGF levels were also signifi-cantly higher in the patients who had de-veloped new syndesmophytes at 2 yearswhen compared with those who had not(579 plus or minus 386 pgmL vs 404 plusor minus 307 pgmL P = 041)

ldquoPatients with elevated VEGF had anodds ratio of 29 for [radiographic] pro-gression and 31 for syndesmophyte for-

mationrdquo Dr Poddubnyy reported Thiswas a little disappointing he noted asCRP and the erythrocyte sedimentationrate had similar predictive power

However in patients at high risk ofprogression namely those with syn-desmophytes already present at base-

line VEGF wassignificantly better thanCRP at predicting both ra-diographic progressionand new syndesmophyteformation or growth

Patients with elevatedVEGF at baseline were366 times more likely tohave radiographic pro-gression and 136 timesmore likely to have newsyndesmophyte formationor growth at 2 years than

were those with levels below 600pgmL In comparison elevated CRPlevels increased the risks by only 24 and25 times respectively

VEGF is an essential mediator of angio-genesis and endochondral ossification DrPoddubnyy observed Itrsquos been shown tohave ldquoa chemoattractive effect on os-teoblasts and mesenchymal progenitorcellsrdquo he added and also stimulate os-teoblast differentiation and bone turnover

While the results are very promisingfurther research is of course requiredThe possible predictive value of VEGF inrelation to spinal radiographic progres-sion in patients treated with tumor necro-sis factorndashalpha inhibitors remains to beseen for example and future studiesshould perhaps look at this question

ldquoWith VEGF we are probably able toimprove our prediction of spinal pro-gression in patients with axSpArdquo DrPoddubnyy said in an interview This isaddition to assessing ldquoclassical factorsrdquosuch as syndesmophytes CRP andsmoking status

Dr Poddubnyy had no disclosures

DR DENIS PODDUBNYYIn patients at high risk ofprogression VEGF wassignificantly better than CRP atpredicting both radiographicprogression and new syndesmo-phyte formation or growth



Spinal MRI Adds Little Value in Diagnosisof Spondyloarthropathy


There is no added benefit of per-forming spinal MRI in the diagnosisof spondyloarthritis the results of

an international multicenter study sug-gest

Around one-quarter of patients withnonradiographic axial spondyloarthritis (nr-axSpA) who had a negative MRI scan of thesacroiliac joints (SIJs) were reclassified as be-ing positive for SpA by a combined evalu-ation of SIJ MRI and spinal MRI scans

However 175 of healthy volunteersand up to 268 of patients with mechan-ical back pain who had a negative SIJ MRIwere also reclassified as having SpA Thisfalse-positive result balances out the valueof combined spinal and SIJ MRI

ldquoCombined MRI added little incremen-tal value compared to SIJ MRI alone for di-agnosis of nr-axSpArdquo said Dr UlrichWeber who presented the findings at theCongress (Ann Rheum Dis 201372145)

ldquoAlthough you get about 20 more pa-tients ndash which is the good news ndash we foundabout the same magnitude of false-positivecontrolsrdquo he said in an interview He addedthat he ldquowas very disappointed with this re-sult and these data need confirmingrdquo DrWeber collected data for the study while atthe Balgrist University Clinic in Zurich andalso as a visiting professor in the rheuma-tology department at the University of Al-

berta EdmontonSIJ MRI is a major criterion of the Assess-

ment of SpondyloArthritis classificationcriteria for ankylosing spondylitis (AS) If apatient is strongly suspected of having ear-ly SpA but this is not yet visible on radiographs then an SIJ MRI is often the nextstep If this is negative however it may beunclear what to do next

ldquoOur question was lsquoWould it help to or-der an additional spinal MRI in this situa-tionrsquo rdquo Dr Weber explained These datasuggest that it is not

The collaborative study included 130 in-dividuals with newly diagnosed back painand aged 50 years or younger who were re-cruited from clinics based in Canada Chi-na Denmark and Switzerland as well as 20healthy control individuals in whom MRIscans of the SIJ and spine were available

The investigators used a clinical exami-nation and pelvic radiography to stratify pa-tients into groups with 50 found to havenr-axSpA 33 with AS and 47 with mechan-ical back pain

Three separate researchers blinded tothe initial stratification read the MRI ofthe SIJ An MRI of the spine was then per-formed 6 months later with a combinedSIJspinal scan done 1-12 months laterThe presence or absence of SpA was de-termined in these scans and comparisonswere made between the results for MRIof the SIJ alone versus spinal MRI alone

as well as for the SIJ alone versus a com-bined read of both the spinal and SIJ MRIscans

Dr Weber noted that he would not rec-ommend changing current practice as a re-sult of this study Further data are eagerlyawaited from an ongoing Danish initiativethat hopes to scan and assess around 2000whole-body MRIs in patients with suspect-ed spondyloarthropathy by the end of theyear ldquoThis study will be very informativeand very important for us because this is alarge sample size Preliminary data onabout 1000 MRIs point in the same direc-tionrdquo he observed

Other data from the study which Dr We-ber presented separately at the meetinglooked at the frequency and possible rea-sons for false-positive results with spinalMRI in the control groups (Ann RheumDis 201372125)

ldquoPatients with mechanical back pain andhealthy volunteers may show spinal MRI le-sions suggestive of spondyloarthritis suchas corner inflammatory lesions or cornerfat lesionsrdquo he explained ldquoWe found thatabout 30 of those controls were misclas-sified as having spondyloarthritis by evalu-ation of the spinal MRI alone so withoutSIJ MRIrdquo said Dr Weber Bone marrowedema and fat infiltration were the MRI le-sions largely responsible for this misclassi-fication

Dr Weber had no disclosures

Arimoclomol Eased Inclusion Body MyositisIn Small Trial of Older Adults


Arimoclomol showed promise as atreatment for the most common type

of inflammatory myopathy in adults overage 50 in a 1-year phase IIa ldquoproof-of-con-ceptrdquo study

Not only was the novel oral agent ldquowelltoleratedrdquo which was the studyrsquos main ob-jective to assess but it also showed earlysigns that it could be effective in the treat-ment of patients with sporadic inclusion

body myositis (IBM) Indeed there was atrend toward slower deterioration in phys-ical function muscle strength and right-hand grip muscle strength for arimoclomolwhen compared against placebo at 8monthsrsquo follow-up

ldquoIBM is an enigmatic diseaserdquo study in-vestigator Dr Pedro Machado said at theCongress ldquoIBM muscle tissue displays[both] inflammatory and degenerativefeaturesrdquo

Dr Machado a senior clinical research

associate at the MRC Centre for Neuro-muscular Diseases at University CollegeLondon (UCL) explained that arimoclo-mol targets the heat shock responseamplifying the expression of heat shockprotein As such it potentially targetsboth the degenerative and inflammato-ry components of the disease ldquoPreviousstudies have only involved agents direct-ly purely at the inflammatory compo-nent of IBM pathology and all were




ineffectiverdquo the researcher observedFor the double-blind study teams based

at UCL and the University of KansasKansas City collaborated to recruit 17men and 7 women (mean age 67 years)who had had IBM for an average of about8 years These patients were randomizedin a 21 ratio to receive active therapy witharimoclomol 100 mg three times daily ormatching placebo for 4 months with fol-low-up lasting for 12 months (AnnRheum Dis 201372164)

The investigators assessed patients forthe development of adverse eventsphysical function using the IBM func-tional rating scale (IBMFRS) and mus-cle strength via manual muscle testingand maximum voluntary isometric con-traction testing (MVICT) at 4 8 and 12months They also measured the pa-tientsrsquo fat-free mass percentage withdual-energy x-ray absorptiometry at 4and 12 months and took muscle biop-sies to assess the levels of heat shockprotein 70 in muscle tissue before and af-ter 4 months of treatment

Fourteen of the 16 patients randomizedto arimoclomol completed 4 months oftreatment 1 patient returned for final as-sessment at 12 monthsrsquo follow-up All

eight placebo patients completed 12months of follow-up

ldquoThe drug was very safe and well toler-ated Compliance was on average 99and we also performed ophthalmologicalassessment and there wereno ophthalmological prob-lemsrdquo Dr Machado said

The most common ad-verse events were gastroin-testinal problems infec-tions and falls althoughthere was no difference be-tween the arimoclomoland placebo groups interms of the frequencytype or severity of theseor other adverse eventsldquoWe have to remind our-selves that this is an elderly populationrdquoDr Machado said noting that the infec-tions seen all responded to standard an-tibiotic therapy

There was one case of hypertension re-quiring prolonged hospitalization in a pa-tient given arimoclomol ldquoThere werealso two cases of hyponatremia in the ari-moclomol group but this was mild tran-sient and asymptomatic and it resolvedwithout treatmentrdquo

At 4 8 and 12 months after baselinescores on the IBMFRS in the arimoclo-

mol versus the placebo arm changed bya respective ndash034 vs ndash088 (P = 239)ndash068 vs ndash250 (P = 055) and ndash203 vsndash350 (P = 538) These data suggest thatless deterioration in physical function oc-

curred with arimoclomolthan with placebo DrMachado said

Muscle strength appearedto improve with active treat-ment as did right-hand gripstrength based on MVICTresults at 8 months that ap-proached significance (126vs ndash054 P = 064)

ldquoA trend towards a slow-er deterioration was ob-served in the arimoclomolgroup for the IBMFRS for

the [muscle] strength score and for thequantitative muscle assessment only forthe right-hand grip assessment at 8monthsrdquo Dr Machado said

ldquoWe believe that these data supportfurther research of arimoclomol in inclu-sion body myositisrdquo he concluded

The study was funded by ArthritisResearch UK a University of KansasNeurology Ziegler Grant and a Univer-sity of Kansas General Clinical ResearchCenter CReFF Grant Dr Machado hadno disclosures

DR PEDRO MACHADO



Medical news tailored exclusively for

rheumatologists

Look for your monthly newsletter edition of

Rheumatology News International


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ltFEFF00560065007200770065006e00640065006e0020005300690065002000640069006500730065002000450069006e007300740065006c006c0075006e00670065006e0020007a0075006d002000450072007300740065006c006c0065006e00200076006f006e002000410064006f006200650020005000440046002d0044006f006b0075006d0065006e00740065006e002c00200075006d002000650069006e00650020007a0075007600650072006c00e40073007300690067006500200041006e007a006500690067006500200075006e00640020004100750073006700610062006500200076006f006e00200047006500730063006800e40066007400730064006f006b0075006d0065006e00740065006e0020007a0075002000650072007a00690065006c0065006e002e00200044006900650020005000440046002d0044006f006b0075006d0065006e007400650020006b00f6006e006e0065006e0020006d006900740020004100630072006f00620061007400200075006e0064002000520065006100640065007200200035002e003000200075006e00640020006800f600680065007200200067006500f600660066006e00650074002000770065007200640065006e002egt ESP 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 ITA (Utilizzare queste impostazioni per creare documenti Adobe PDF 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SUO 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 SVE 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 ENU (Use these settings to create Adobe PDF documents suitable for reliable viewing and printing of business documents Created PDF documents can be opened with Acrobat and Adobe Reader 50 and later) gtgtgtgt setdistillerparamsltlt HWResolution [2400 2400] PageSize [612000 792000]gtgt setpagedevice


Welcome to the EULARReport 2013

The Annual European Congress of Rheumatology hosted by the Eu-ropean League Against Rheumatism (EULAR) is recognized as the pri-mary platform for European rheumatology education and information

exchange in the world This yearrsquos EULAR Congress was no exception Over14000 attendees came to Madrid from 120 countries around the world (60from Europe) to hear the best in rheumatology research and clinical advancesThe scientific program contained presentations selected from 3889 abstractssubmitted

We hope that this report is of interest and value for those of you who wereunable to attend the EULAR Congress in Madrid and for those who did (sincenobody can expect to see all of the best of the Congress while there) TheEULAR Report brings you highlights of some of the best presentations fo-cusing on the sort of clinical and therapeutical findings that change the wayrheumatologists practice medicine

We hope that you will enjoy these accounts of the latest in rheumatologyclinical and translational research

Many of the research reports that you will find here also include accessto video interviews with the presenters

For details about the next EULAR Congress to be held 11-14 June 2014in Paris please visit wwweularorg

PROF MAXIME DOUGADOSPast President of EULARProfessor of Rheumatology at ReneacuteDescartes UniversityChief of the Department of Rheumatologyat Cochin Hospital Paris

The eular ReportAnalysis of Key Research Presented at the 14th Annual European Congress of Rheumatology

President IMNG Medical MediaAlan J ImhoffDirector IMNG Society PartnersMark BrancaEditorJeff EvansDesignerLisa MarforiProduction ManagerMaria Aquino

Copyright copy 2013 IMNG MedicalMedia All rights reserved Nopart of this publication may be reproduced or transmitted in anyform by any means without priorwritten permission of the Publisher IMNG Medical Mediawill not assume responsibility fordamages loss or claims of anykind arising from or related to theinformation contained in this publication including any claimsrelated to the products drugs orservices mentioned herein

Cover image Bernardo Diacuteaz

PROF MAURIZIO CUTOLOPresident of EULARProfessor of Rheumatology and InternalMedicineDirector of Research Laboratory andAcademic Unit of Clinical RheumatologyDepartment of Internal MedicineUniversity of Genova Italy



















Source Dr Smolen













DR JOSEF S SMOLEN








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DR HEATHER GLADUE




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SIT

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DR STEPHEN KELLY









































































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DR PEDRO MACHADO




rheumatologists






















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DR PEDRO MACHADO




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DIC

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DR STEPHEN KELLY









































































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DR PEDRO MACHADO




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KP

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ME

DIC

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ME

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SA

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ME

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DR PEDRO MACHADO




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SA

RA

FR

EE

MA

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ME

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NIC

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DR PEDRO MACHADO




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FR

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ME

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ME

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CO

UR

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NIC

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DR PEDRO MACHADO




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NIC

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DR PEDRO MACHADO




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NIC

KP

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AR

IIM

NG

ME

DIC

AL

ME

DIA























































































































DR PEDRO MACHADO




rheumatologists


























































































































DR PEDRO MACHADO




rheumatologists






rheumatologists





eular 2013 post digital · 11. treatment with tofacitinib can be considered after patients fail...

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