w w w . r e u m a t o l o g i a . c o m . b r
REVISTA
BRASILEIRA
DE
REUMATOLOGIA
Original
article
Sarar
cohort:
disease
activity,
functional
capacity,
and
radiological
damage
in
rheumatoid
arthritis
patients
undergoing
total
hip
and
knee
arthroplasty
Bernardo
Matos
da
Cunha
a,∗,
Sandro
Barbosa
de
Oliveira
a,
Leopoldo
Luiz
dos
Santos-Neto
b aHospitalSARAH,Brasília,DF,BrazilbClínicaMédica,UniversidadedeBrasília,Brasília,DF,Brazil
a
r
t
i
c
l
e
i
n
f
o
Articlehistory:
Received10June2014
Accepted23December2014
Availableonline22July2015
Keywords:
Rheumatoidarthritis
Arthroplasty
Radiologicaldamage
Functionalcapacity
a
b
s
t
r
a
c
t
Objectives:TheSararcohortconsistsofpatientswithrheumatoidarthritisandjuvenile
idio-pathicarthritiswhounderwenthiporkneearthroplastiesathospitalSARAH-Brasília.The
objectiveofthisstudywastoevaluateclinicalandlaboratoryfactorsassociatedwith
dis-easeactivity,functionalcapacityandradiologicaldamageinrheumatoidarthritispatients,
participantsinthiscohort.
Methods:Cross-sectionalstudy,withdatacollectionachievedfrommedicalrecordsreview.
Results:Thirty-twopatientswereincluded,withameantimeofdiseaseonsetof240months.
Nineteenpatientsunderwenttotalkneeand17totalhiparthroplasty.Therewasa
pos-itivecorrelation betweenmaximumdoseofmethotrexateand ClinicalDiseaseActivity
Index(R=−0.46,p=0.011),andanegativeonewithSimplifiedErosionandNarrowingScore
(R=−0.58,p=0.004).SimplifiedErosionandNarrowingScorevalueswerehigherinpatients
withrheumatoidfactor(p=0.005)andanti-cycliccitrullinatedpeptideantibody3positivity
(p=0.044),inthosewithhigherrheumatoidfactor(p=0.037)andanti-cycliccitrullinated
peptideantibody3(p=0.025)titers,andlowerinpatientswithfamilyhistoryofrheumatoid
factor(p=0.009).HealthAssessmentQuestionnairevalueswerehigherinolderpatients
(p=0.031).Inmultiplelinearregression,only“maximumdoseofmethotrexate”and
“fam-ilyhistory”remainedwithsignificantassociationwithSimplifiedErosionandNarrowing
Score(r2=0.73,p<0.001forbothvariables).Inthemodelevaluating“ClinicalDiseaseActivity
Index”only“maximumdoseofmethotrexate”remainedsignificantlyassociated(r2=0.35,
p=0.016).
Conclusion:IntheSararcohort,clinicalandlaboratoryfactorswererelatedtodiseaseactivity,
functionalcapacityandradiologicaldamage,similartostudiesevaluatingpatientswith
lowerdiseaseduration.
©2015ElsevierEditoraLtda.Allrightsreserved.
∗ Correspondingauthor.
E-mail:[email protected](B.M.daCunha).
http://dx.doi.org/10.1016/j.rbre.2015.05.005
Coorte
Sarar:
atividade
de
doenc¸a,
capacidade
funcional
e
dano
radiológico
em
pacientes
com
artrite
reumatoide
submetidos
à
artroplastia
total
de
quadril
e
joelho
Palavras-chave:
Artritereumatoide
Artroplastia
Danoradiológico
Capacidadefuncional
r
e
s
u
m
o
Objetivos: AcoorteSararécompostaporpacientesportadoresdeartritereumatoide(AR)
eartriteidiopáticajuvenil(AIJ)submetidosaartroplastiasdequadrilejoelhonohospital
SARAH-Brasília.Oobjetivodesteestudofoiavaliarfatoresclínicoselaboratoriais
associa-dosàatividadededoenc¸a,capacidadefuncionaledanoradiológicoempacientescomAR,
participantesdessacoorte.
Métodos: Estudotransversal,comcoletadedadosemrevisãodeprontuário.
Resultados: 32pacientesforamincluídos,comtempomédiodeiníciodadoenc¸ade240
meses.DezenovepacientesforamsubmetidosaATJe17,aATQ.Foiencontradacorrelac¸ão
positivaentredosemáximade metotrexato(MTX)durantea evoluc¸ãoe ClinicalDisease
Activity Index (CDAI)(R=-0,46, p=0,011)enegativacomSimplified Erosionand Narrowing Score(SENS)(R=-0,58,p=0,004).ValoresdeSENSforammaioresnospacientescomfator
reumatoide(FR)(p=0,005)eanticorpoanti-peptídeocíclicocitrulinado3(anti-CCP3)
posi-tivo(p=0,044),noscommaiorestítulosdeFR(p=0,037)eAnti-CCP3(p=0,025)emenores
nospacientescomhistóriadefamiliardeAR(p=0,009).ValoresdeHAQforammaioresem
pacientesmaisidosos(p=0,031).Naregressãolinearmúltipla,somente“dosemáximade
MTX”e“históriafamiliar”permaneceramcomassociac¸ãosignificativacomSENS(r2=0,73,
p<0,001paraambasasvariáveis).Nomodeloqueavaliou“CDAI”,apenas“dosemáximade
MTX”permaneceucomassociac¸ãosignificativa(r2=0,35,p=0,016).
Conclusão: NacoorteSarar,fatoresclínicoselaboratoriaisestiveramrelacionadosà
ativi-dadededoenc¸a,capacidadefuncionaledanoradiológico,semelhantementeaestudosque
avaliarampacientescommenortempodedoenc¸a.
©2015ElsevierEditoraLtda.Todososdireitosreservados.
Introduction
Rheumatoid arthritis (RA) is a common disease in Brazil,
affecting0.2–1%oftheBrazilianpopulation.1Brazilian
guide-lines fortreating RArecommend early use of atleast one
disease-modifyinganti-rheumatic drugs(DMARDs),withor
without the use of corticosteroids, since the onset of the
disease.2Themainobjectiveistopreventoratleastslowthe
progressionofradiographicjointdamage,whichcanleadto
deformitiesandfunctionaldisability,withreducedqualityof
lifeandworkcapacity.However,thetreatmentofRAisoften
suboptimalinourenvironment3and,therefore,manypatients
developsecondaryosteoarthritis,requiringsurgicaltreatment
withtotalarthroplasties,significantlyincreasinghealthcare
costs.4
TheSARAHNetworkisareferencecenterforrehabilitation
inBrazil,withunitsinseveralBrazilianstates,includingthe
FederalDistrict.Inthiscontext,theinstitutionfocusesonthe
treatmentofpatientswithRAorjuvenileidiopathicarthritis
(JIA)atanadvancedstage,withpermanentsequelaeofthe
diseasebymeansoforthopedicsurgeriesandrehabilitation.
TheSararcohortconsistsofadultpatientsofallagegroups,
patientswithlong-standingRAorJIA,withgreatfunctional
disabilityandextensiveradiologicaldamage,participatingin
arehabilitationprogramandhavingorthopedictreatmentfor
sequelaeofthediseaseinthehospitalSARAH-Brasília.Itsgoal
istoevaluatethesepatients’long-termprogressafter
under-goingprimaryorreviewtotalhipand/orkneereplacement.
Patientsareusuallyreferredfrompublicorprivate
rheuma-tologyclinics,forrehabilitation.Theinclusionofpatientsin
thecohortbeganinOctober2008andendedinJanuary2013.
Aftertheinitialinclusion,patientswereevaluatedinsomeof
theirfollow-upvisitswiththeOrthopedicsteam.
Theclinical characteristics ofpatientswith RAwhoare
candidatesfororthopedicsurgerycaninfluencethedegreeof
disabilityandinstabilityatwork,5inflammatoryactivityand
radiologicaldamage.6Therefore,theobjectiveofthisstudyis
toevaluatetheclinical,radiologicalandlaboratoryprofileof
RApatientsfollowedbytheSararcohort,andevaluatewhich
factorsareassociatedwithdiseaseactivity,functional
capac-ityandradiologicaldamage.
Methods
Studydesign
Cross-sectionalanalysis ofdatafrom theSarar cohortwith
datacollectionachievedfrommedicalchartreview.
Inclusionandexclusioncriteria
Weincludedallpatientsaged≥18yearsadmittedattheAdult
OrthopedicsandNeurosurgeryDepartmenttoundergototal
hip(THA)orknee(TKA)arthroplastyatthehospital
Sarah-Brasilia, who had RAwith diagnosis established according
explainedabove,patientinclusionoccurredbetweenOctober
2008andJanuary2013.
RApatientshavebeenexcludedif:theindicationof
arthro-plasty was due to avascular necrosis, other inflammatory
diseases justified the articular condition better than RA,
and patients who underwent previous arthroplasty during
theinclusionperiod.Specificallyinthisstudy,weexcluded
patientswithJIA.
Datacollection
Thestandardized assessmentwas performed by means of
theelectronicmedicalrecorddatareview,supplementedby
patient interview when needed, one day before the date
ofthe proposedsurgery. Thefollowingdatawere recorded:
duration of disease; time interval between the onset of
symptoms and the correct diagnosis; date of initiation
of treatment with DMARDs with description of
medica-tions on prior and current use, including the dose; time
of follow-up with a rheumatologist; preoperative
orthope-dic diagnosis; associated autoimmune conditions; history
of smoking; family history ofRA; presenceof rheumatoid
factor (RF) and anti-cyclic citrullinated peptide antibody 3
(anti-CCP3), both byELISA, when available,with the most
recent date of examination in the medical record being
considered.
InflammatoryactivitywasassessedwiththeClinical
Dis-easeActivityIndex(CDAI),8whichtakesthecountoftender
andswollenjoints,togetherwiththeoverallhealth
assess-mentscorebythepatientandthephysician,byvisualanalog
scale,intoaccountforitscalculation.
Preoperative functional capacity was assessed with the
Health Assessment Questionnaire-Disability Index (HAQ)
translatedandvalidatedforthePortugueselanguage,and
self-administered.9,10
Theestablishedjoint damagewasassessedwithsimple
digitalradiographsofhandsandfeetusingtheSimplified
Ero-sionNarrowingScore(SENS),11whichcountsthenumberof
jointsinwhichthereisthepresenceofjointspace
narrow-ingand/orerosions.Forthisassessment,weusedtheEfilm
Workstationsoftwareversion2.1.2,whichallowedtheuseof
imagemagnificationfeatures.Arheumatologistexaminedall
radiographs(BMC).
ThestudywasapprovedbytheResearchEthicsCommittee
oftheSARAHNetwork,registered atPlataformaBrasilwith
thenumber07477412.2.0000.0022.
Statisticalanalysis
Descriptive analysis was performed. RF values and
anti-CCP3 were divided into four categories, with the former
accordingtothequartiles,andthelattertonegative,weakly
positive, moderatelypositive and stronglypositive,
accord-ingtothe manufacturer’s references.Spearmancorrelation
testswereperformedbetweencontinuousindependent
vari-ables and the dependent variables (CDAI, HAQand SENS).
Mann–Whitney U test was performed for comparison of
meansincludingindependentvariableswithtwocategories,
and the Kruskal–Wallis H test for comparison of means
including independent variables with morethan two
cate-goriesbeingconducted.
Subgroupanalysiswasperformedamongpatients
under-goingTHAandTKA.
Multiple linearregression modelwas developed,
includ-ing the independent variables with significant association,
assuminganormaldistributionofdata.
To verify the intra-examinervariability of evaluationof
radiographs, wecalculatedthe intraclasscorrelation
coeffi-cient,model3.112and performedpairedt-testincluding 10
patientswhowererandomlyselectedbyacomputerprogram
amongthestudysample.
ThesoftwareusedwastheSOFAversion 1.4.0and SPSS
version21.
Results
Thirty-twopatientswereincluded,with28femalepatients.
Themeanagewas59yearsold(40–84).Mostpatientslived
in theFederal District(24 individuals), but 5patients from
thestateofMinasGerais,onefromthestateofParaíba,one
fromTocantinsand1fromSaoPaulowereincluded.Patients
referredbytheBrazilianNationalHealthService(SUS)totaled
44%ofcases;withinpatientsfromplacesotherthanthe
Fed-eralDistrict,onlyonewasfollowedinapublichealthcenter.
Seventeenpatientswereretired.Nineteenpatientsunderwent
TKAand17,THA.
Five patients were not regularlyfollowed bya
rheuma-tologist.Forty-eightpercentofpatientshadmissed
rheuma-tologist follow-up foraperiod, sincethe first contactwith
the specialist.Amongthepatientswho hadintervals
with-outrheumatologymonitoring,unaccompaniedaveragetime
was45months(0–432).
Theaveragetimebetweentheonsetofthediseaseandthe
surgerywas240months(47–506)andthemeantimebetween
onsetofsymptomsandthediagnosisofRAwas27months
(1–369).Thirteenpatientswere currentorprevioussmokers
and16patientshadfamilyhistoryofRAinfirst-degree
rela-tives.
Eighty-seven percent ofthe patients had active disease
(39% mild activity, 23% moderate and 26% severe), with a
meanCDAIof14.7(0.5–56.4).Theaveragedurationof
morn-ing stiffness was 25min(0–240). The averageHAQ was1.8
(0.25–2.875).
Twenty-seven patients were taking DMARDs (Table 1),
although3ofthesepatientshadreportedhavingused<80%of
doses.Consideringthepreviousandcurrentuse,
methotrex-ate(MTX)wastakenby84%ofthepatientsduringfollow-up,
butonly41%wereoncurrenttreatment.Themaximumdose
prescribed byrheumatologists inthe courseofthe disease
wasonaverage15.1mg(2.5–20).Fivepatientshaveneverbeen
treated with MTX, including one with 115 months of
dis-easeduration.Onlytwopatientsdidnotreceiveantimalarial
drugsduringfollow-up.Leflunomidewastakenby66%ofthe
patients,sulfasalazineby31%andgoldsaltsby22%.Among
thebiologicaldrugs(receivedby31%ofthepatients),themost
frequentwereetanerceptandadalimumab,withfourcases
Table1–Currentuseofdisease-modifyingdrugs(DMARDs).
DMARD n Dose
Mean SD min–max
Methotrexate(mg/week) 13 14.4 2.9 2.5–20
Leflunomide(mg/day) 15 20 0 20
Sulfasalazine(mg/day) 2 750 350 500–1000
Chloroquine(mg/day) 5 250 0 250
Hydroxychloroquine(mg/day) 3 333.3 115.5 200–400
Infliximab(mg/dose) 1 200 0 200
Etanercept(mg/week) 2 50 0 50
Adalimumab(mg/dose) 3 40 0 40
Rituximab(mg/dose) 2 2000 0 2000
Abatacept(mg/dose) 1 500 0 500
Complications directly related to surgery occurred in sevencases, with three being dislocationsof prosthesis, a periprostheticfracture,asurgicalsiteinfection,agraft infec-tionandaheterotopicossification.
Amongthe associatedautoimmune conditions,the only onepresentwasthyroidautoimmunedisease(hypo-or hyper-thyroidism)in34%ofthepatients.
RFwaspositivein51%ofthepatients,withameanvalueof 371U/ml(29–3140).Theanti-CCP3waspositivein62%ofcases, beingweakly positive in3%,moderate in9%, and strongly positivein50%.TheaverageSENSwas34.8(1–75).
Whenthedependentvariable“CDAI”wasanalyzed,a neg-ativecorrelationwasfoundwithtimeofdiseaseonset,anda positiveonewiththemaximumdoseofMTX.Moreover,a posi-tivecorrelationwasfoundbetweenHAQandage,andbetween SENSandthemaximumdoseofMTX(Table2).
Oncomparisonofmeans,whenthedependentvariables
“CDAI”and“HAQ”wereassessed,nosignificantassociations
Table2–SpearmanCorrelationTestsamongcontinuous independentvariables,HealthAssessment
Questionnaire(HAQ),ClinicalDiseaseActivityIndex (CDAI)andSimplifiedErosionNarrowingScore(SENS).
R CI p
CDAI
Age −0.04 −0.39;0.32 0.816
Timeonset −0.46 −0.70;−0.12 0.011 time-diag 0.17 −0.20;0.50 0.365 MTXMaxDose 0.55 0.22;0.77 0.003
HAQ
Age 0.39 0.04;0.65 0.031
Timeonset 0.07 −0.3;0.42 0.704 time-diag 0.08 −0.29;0.43 0.676
MTXMaxDose 0.01 −0.37;−0.39 0.957
SENS
Age −0.09 −0.45;0.29 0.653
Timeonset 0.32 −0.07;0.62 0.101 time-diag 0.16 −0.23;0.51 0.431 MTXMaxDose −0.58 −0.80;−0.22 0.004
tonset-diag,timespanbetweensymptomsappearanceand diag-nosis;MTX,methotrexate.
werefound.Intheanalysisofthedependentvariable“SENS”, apositiveassociationwasfoundwiththepresenceofRFand Anti-CCP3,andanegativeonewithsmokingandfamily his-toryofRA.Patientswerestratifiedintocategories,according tothetitersofRFandAnti-CCP3,withthehighesttitersbeing associatedwithhigherSENSvalues(Table3).
Themultiplelinearregression modelincludedthe
clini-calandlaboratoryvariableswithsignificantassociationwith
SENS and CDAI. Regarding the dependent variable “SENS”,
twomodelswereconstructed,oneincludingtheRFand
anti-CCP3ascategoricalvariables(presentorabsent)andanother
oneasordinalvariables.Inbothofthem,onlythevariables
“maximumdoseofMTX”and“familyhistory”remainedwith
significantassociation(p<0.001inbothvariables).Thefinal
modelexplainedapproximately73%ofthevariabilityofSENS.
Inthemodelthatevaluatedtheindependentvariable“CDAI”,
Table3–Mann–WhitneyandKruskal–Wallistestsfor comparisonamonggroupswithpresenceorabsenceof clinicalandlaboratoryvariables.
Variable CDAI HAQ SENS
p
PositiveRF 0.563 0.611 0.005
RFtiter(1–4) 0.532 0.181 0.037
Anti-CCP3+ 0.351 0.301 0.044
Anti-CCP3titer(1× 4) 0.575 0.458 0.025
Gender 0.86 0.616 0.87
Smoking 0.936 0.054 0.08
FamilyhistoryofRA 0.58 0.406 0.009
MTX 0.724 0.204 0.674
LFN 0.833 0.611 0.51
SSZ 0.151 0.719 0.811
Antimalarial 0.127 0.778 0.964
GoldSalts 0.108 0.124 0.466
Biologicaldrug 0.057 0.33 0.98
TKA 0.776 0.109 0.502
only“maximumMTXdose”remainedsignificantlyassociated
(r2=0.35,p=0.016).
There were no significant differences between patients
undergoingTHAandTKA,forCDAI,HAQandSENS.
Theintraclasscorrelationcoefficientfortheevaluationof
10radiographswas 0.92(95% CI0.73–0.98)and the average
differenceamongpeerevaluationswas3.4(SD7.183).There
wasnosignificantdifference(p=0.169).
Discussion
Ourresultsidentified possibleimprovementsthatcould be
implementedinthe managementofpatientswithRAwho
arereferredforrehabilitationand surgery.Thesmall
num-berofpatientswho were incurrent useofMTX,the main
drugforRAtreatment,isnotable.Thiscanbeexplainedin
partbecausetheyarelong-standingpatients,whoinmany
cases were exposed to medication for a long time, which
canincreasethechanceofmedicationdiscontinuationdueto
adverseevents13,14mainlyintheliver.15 Furthermore,some
patientsmightnothavehadagoodresponsetothe
medica-tion.Ontheotherhand,49%ofthepatientshadmoderate
tosevereinflammatorydiseaseactivity,whatweconsideran
inappropriatesituationintheperioperativesetting.This
can-notbejustifiedonlybytheseverityofthecases,sincemany
patientshadsuboptimaldoseofDMARDs.Jointswith
dam-agemayhavepersistentinflammation.If drugtherapywas
optimized, patients with active disease could express less
painsymptomsinthejointwherethesurgerywasindicated,
andsurgerycouldbepostponed.Additionally,diseaseactivity
makespatientsmoredisabled,whichcanreducecompliance
torehabilitationactivities.
ThefrequencyofRFpositivityand anti-CCP3 waslower
thanthatreportedintheinternationalliterature,butsimilarto
thatfoundinBrasiliacohort,16composedofearlyRApatients
whoseinitialbloodsampleswerecollectedbeforetreatment.
Inthatstudy,RFtitersincreasedafteroneyear,whichmay
explainthemeantiterofRFbeingmuchhigherthaninour
study.ThesedatacontrastwiththedescriptionbyBosetal.,
onwhichareductionofRFlevelsorevennegativationoftest
resultswasobservedinsomeofthecasesafterinitiationof
adalimumabtreatment,17andwiththestudybyVazetal.,in
whichtherewassignificantreductioninanti-CCPtitersduring
treatmentwithinfliximab.18Thesefindingsmayberelatedto
specificcharacteristicsofanti-TNFinhibitors.
Similarlytothisstudy,othergroupshavefoundno
corre-lationbetweenthepositivityortitersofRFwithfunctional
capacityanddiseaseactivity.19,20TheassociationbetweenRF
positivityandradiographicprogressionisknown,especiallyin
patientswithearlydisease21,22buthowthejointdamage
accu-mulatesoverdecadesisnotknown.Inthisstudy,therewas
noindependentcorrelationbetweenRFandSENS,butpatients
ofanaverageof20yearsofdiseaseonsetwithmany
accumu-latedjointdamagewereevaluated.Notethatnocorrelation
wasfoundbetweenageandradiologicaldamage,suggesting
thatdamageappearancecangetstableovertime.
Therewas apositivecorrelation betweenage and
func-tionalability,irrespectiveofthedegreeofradiologicaldamage,
suggestingthatotherfactorsareinfluencingHAQ,for
exam-ple,thenaturalagingprocess.23
Inourstudy,smoking wasnotindependentlyassociated
togreaterradiographicprogression.Theresultscontrastwith
thoseofaprospectivestudybyVesperinietal.,whorecently
showedalowerriskofprogressioninpatientswithearlyRA,24
butareinagreementwiththeresultsoftwootherstudies.25,26
Conversely, the study by Ruiz-Esquideet al. demonstrated
greaterradiographicprogressioninsmokers.27Therefore,the
associationbetweensmokingandradiographicprogressionis
stillcontroversial.
RegardingfamilyhistoryofRA,theresultsofthisstudy
con-tradictthosebyRojas-Villajagaetal.,whichdemonstratedthat
earlyRApatientswithafamilyhistorydevelopedradiographic
damagemorequickly,althoughthecumulativedamagewas
notevaluated,28aswasthecaseinourstudy,whichevaluated
patients withlong-standingdisease.Factorssuchasethnic
differences,diseaseduration,differencesintreatmentwith
DMARDs, and radiographic evaluationmethods canbe the
originofthisdisparity.
Patientswithlong-standingdiseaseactivityhaveahigher
cumulative radiological damage,29 which may explain the
useoflargerpreviousdosesofMTXinpatientswithhigher
SENSandCDAIvalues,becausetheyprobablyhad,
through-outevolution,activityofthediseasethatismoredifficultto
control.
TheSararcohort,inaway,makesaninteresting
counter-pointtothe Brasíliacohort, onceitcomestopatientswith
advanced disease, from the same region of Brazil. To our
knowledge,thisisthefirststudyinBrazilthatassessed
dis-easeactivity,functionalcapacityandradiologicaldamagein
patientswithRAofsuchlong-standingdisease,whichis
inter-estinginatimewhenalleyesarefocusedonpatientswith
earlyRA.Currently,achangeintheevaluationand
manage-mentofpatientswithRAundergoingrehabilitationtreatment
atSARAH-Brasiliahospitalisbeingplanned,motivatedbythe
resultsofthis study,so thatsuchpatients are groupedfor
rehabilitationataspecializedclinic.
Thisstudyhaslimitations.Itisacross-sectionalstudy,the
findingsofwhichrequireconfirmationinprospectivestudies;
temporaldataandmaximumdosesofDMARDswerereported
bythe patients who recoveredit from memory,which can
leadtoinaccuracies(e.g.,theassessmentoffamilyhistory),
consideringthe long termofthe disease;RFdetection had
greattemporalvariationprecedinghospitalization,soinsome
cases theymay not haverepresented the current immune
status of patients; due to technical reasons related to the
bidimensionality ofthe radiographs, it was notpossibleto
assesstheSENSofapatientwithseveredeformities,which
excludedfromtheanalysisacasewithverysevereradiological
changes.
In summary,patients ofthe Sarar cohort treated atthe
hospital SARAH-Brasilia, receiveda latediagnosis ofRAin
theirhealthcentersoforigin.Abouthalfofthepatientshad
moderatetosevereinflammatoryactivity,withnon-optimized
treatmentaccordingtotheconsensusoftheBrazilian
Soci-ety ofRheumatology2and the recommendationsoftheRA
TreatToTarget.30PatientswithfamilyhistoryofRAhadless
radiologicaldamage,whilepatientsusinghighermaximum
functionaldisability.ThemaximumdoseofMTXduring
evo-lutionwasassociatedwithhigherdiseaseactivity.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
Acknowledgement
LuizGuilhermeNadalNunes,forhishelponstatisticaltests
planningforassessmentoftheintra-examinervariabilityin
radiographanalysis.
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