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Objectives

MakeWayforRA:
AnOverviewofRheumatoidArthritis

1. Recognizethepathophysiology,clinicalpresentation,and complicationsofrheumatoidarthritis. 2. Explaintheavailabletreatmentsoptionsforpatients presentingwithRA,including:

Preferredtreatments,givenspecificpatientcharacteristicsand treatmenthistory. Differencesinmechanismofactionamongstallavailabletreatments. Sideeffectsandcontraindicationsofeachavailabletreatment.

3. CounselpatientsregardingthepossiblesideeffectsofRA agentsandtheirpropermanagement. MikeCrowe,PharmD ClinicalPharmacist May15,2012

Introduction14
Chronic,autoimmunedisease Unknowncause Complicationsnotlimitedtojoints Possibly increasing in incidence Possiblyincreasinginincidence Treataggressively Targetclinicalremission

Epidemiology3,4
Prevalence o 1%onaverage o 0.1%inruralAfricans o 5% in Pima Blackfeet Chippewa Indians 5%inPima,Blackfeet,ChippewaIndians Racedoesnotappeartoimpact Peakonsetbetween50and75

RUAwakeforRA?
Whatistherelationshipbetweengenderand rheumatoidarthritis? a. Menaremorelikelytodevelop a Men are more likely to develop b. Womenaremorelikelytodevelop

Epidemiology3,4
Womenhave23timesgreaterrisk Ages1545,6timesgreater Estrogenthoughttoplayarole

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Epidemiology3,4
Identicaltwinhas30timeshigherrisk Childrenhave6timeshigherrisk SharedEpitope o Human Lymphocyte Antigen (HLA) HumanLymphocyteAntigen(HLA) o HLADR1,HLADR4,HLADR14 o FoundinmajorityofRApatients o DR4confers3.5xgreaterrisk o NotrequiredforRA

EnvironmentalRiskFactors1,4
Negative o Cigarettesmoking o Infection o Occupational exposure Occupationalexposure Protective o Alcohol o Breastfeeding o Highersocioeconomicstatus

Pathophysiology1,3
Autoimmunedisease Nolongerdifferentiatebetweenselfandnonself Synovialandotherconnectivetissuesareattacked Leadstochronicinflammationofsynovialtissue Inflamedsynovialtissue(pannus)proliferates Inflamed synovial tissue (pannus) proliferates Proliferationleadstodestructionofboneandcartilage

Pathophysiology1,3,5
CitrullinationduetoerrorsinDNAtranscription o Fibrinogen o Collagen o Others Citrullinated peptide may be initiating antigen Citrullinatedpeptidemaybeinitiatingantigen AntigenpresentingcellspresenttoTcell o Dendriticcells o Macrophages o Bcells StimulatesTcellsandBcells

Pathophysiology1,3,5
Bcells Plasmacells autoantibodies(RF,antiCCP) PossessCD20cellsurfaceprotein Tcells T cells CD4+proinflammatory(TNF,IL1,IL6) Activationrequirescostimulation(CD80/CD86) Proinflammatorycytokinesproducedbyother immunecellsandarenotlimitedtoTNF,IL1,IL6

ClinicalPresentation3,6
Classic Acute Palindromic Monoarthritis
Insidiousonset Mostcommonpresentationtype

Occursinuptoonethird Associatedwithmusclepain,fatigue,fever,weightloss,depression

Episodicjointinvolvementforhourstodays Absenceofsymptomsfordaystomonths 40%developRA

Typicallyinvolvesalargejoint(e.g.,knee,shoulder) Maybedaysorweeksbeforemultiplejointsaffected

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SignsandSymptoms3,6
Typically>6wksofjointpain/stiffness o Mostoftensymmetrical o Maybeginunsymmetrical Muscle pain/fatigue in afternoon Musclepain/fatigueinafternoon Generalfatigueandweakness Lowgradefever Lossofappetite

LaboratoryMarkers3,6
RFin6070%ofpatients AntiCCPantibodiescommon Elevatederythrocytesedimentationrate(ESR) Anemiaandthrombocytosiscommon Anemia and thrombocytosis common IncreasedWBCcountsinjointfluid Radiographicfindings o Jointnarrowing o Erosions

RUAwakeforRA?
Comparedtoosteoarthritis,thejointsofthehips, knees,andspineare: a. MorelikelytobeinvolvedinRA a More likely to be involved in RA b. LesslikelytobeinvolvedinRA

ArticularManifestations3,6
Jointsaffecteddifferfromosteoarthritis(OA) Morningstiffness>30mins Adequateexerciserequired Deformationinlaterstages

ArticularManifestations3,6

ExtraarticularManifestations3,6
Cardiacinvolvement Rheumatoidnodules Vasculitis Pulmonarycomplications Pulmonary complications Ocularmanifestations FeltysSyndrome

AllJoints
Pain Swelling Tender

Hands/Wrists
Lossofgrip strength Inabilityto perform activitiesofdaily livingorwork activities

Knees/Feet
Popliteal/Baker cystsinknees Hammertoe, bunions,calluses infeet Instabilityor abnormalgait

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CardiacImpact3,7,8
IncreasedcardiovascularriskinRApatients o Heartfailureriskdoubled o Riskofcardiovasculardeathincreased50% Risk reduced with treatment Riskreducedwithtreatment RarecomplicationsofRA:
o Pericarditis o Myocarditis o Conductionabnormalities

RheumatoidNodules3,7,8
Palpablenodulesin2035%ofpatients o RheumatoidFactor o Erosivedisease Most common on extensor surfaces of arms Mostcommononextensorsurfacesofarms Usuallyasymptomatic;rarelytreated Localsteroidinjectionmaycauseregression

Vasculitis3,7,8
Inflammatorydestructionofbloodvessels Occursin<1%ofRApatients Typicallyinsmallvessels,leadstoinfarcts Generallynotofclinicalsignificance Generally not of clinical significance Mayleadtobreakdownofskin,producing difficulttotreatulcers

PulmonaryComplications3,7,8
Pleuraleffusions Pulmonaryfibrosis Rheumatoidnodulesinlungtissue Interstitialpneumonitis Interstitial pneumonitis Secondaryinfection

OcularInvolvement3
Keratoconjunctivitis Scleritis SjogrensSyndrome Rheumatoidnodulesinsclera Rheumatoid nodules in sclera

FeltysSyndrome3,7
RAwithsplenomegalyandneutropenia o +/ Anemia o +/ Thrombocytopenia o +/ Leg ulcers (rarely) +/ Legulcers(rarely) susceptibilitytoinfection Splenectomydoesnotimprove BestapproachistocontrolRA

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1987ACRDiagnosis9
> 4CriterionIndicatesRA
Arthritisof3 Arthritisof orMoreJoint or More Joint HandJoints Areas

2010ACR/EULARDiagnosis9,10
A. JointInvolvement
Serum RF Radiographic Changes 1largejoint 210largejoints 13smalljoints 410smalljoints >10joints(> 1small) NegativeRFandnegativeACPA LowpositiveRForlowpositiveACPA HighpositiveRForhighpositiveACPA NormalCRPandnormalESR AbnormalCRPorabnormalESR <6weeks > 6weeks 0 1 2 3 5 0 2 3 0 1 0 1

TotalScore> 6IndicatesRA >

Morning Stiffness

Symmetric Arthritis

Nodules

B.

Serology

> 6weeks

C. D.

AcutePhaseReactants

DurationofSymptoms

RUAwakeforRA?
PatientLMpresentswiththefollowing characteristics.Whatisyourdiagnosis?
5jointsineachhandareswollen/tender High positiveRForhigh positiveACPA Highpositive RF or highpositive ACPA AbnormallyhighESR Symptomspersistingfortwomonths

GoalsofTherapy3,11
Maintainor ImproveQOL

ReducePainand Inflammation

a. LMhasRA b. LMdoesnothaveRA

Target Low TargetLow Disease Activityor Remission

PreventingJoint Destruction

MaintainAbilityto PerformDailyActivities

DiseaseActivityInstruments11
Instrument Patient ActivityScale(PAS)orPASII (range010) RoutineAssessmentofPatientIndexData3 (range010) ClinicalDisease ActivityIndex (range076.0) DiseaseActivityScorein28Joints (range09.4) SimplifiedDiseaseActivity Index (range086.0) ThresholdsofDiseaseActivity Levels
Remission:0 to0.25 Low:0.26 to3.7 Moderate:3.71to<8.0 High:> 8.0 Remission:0 to1.0 Low:>1.0to2.0 Moderate:>2.0to4.0 Moderate: > 2.0 to 4.0 High:>4.0 to10 Remission:< 2.8 Low:>2.8to10.0 Moderate:>10.0to22.0 High:>22 Remission:<2.6 Low:> 2.6to<3.2 Moderate:> 3.2to< 5.1 High:>5.1 Remission:< 3.3 Low:>3.3to< 11.0 Moderate:>11.0to< 26 High:>26

TreatmentOptions3
NonPharmacological
ImproveFunction ReduceRisk

SymptomaticTherapies
NonSteroidal AntiInflammatoryDrugs(NSAIDs) Corticosteroids

DiseaseModifyingAntirheumaticDrugs(DMARDs)
TraditionalDMARDs BiologicDMARDs

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RUAwakeforRA?
Whichofthefollowingareappropriate nonpharmacologicalrecommendationsfora patientdiagnosedwithRA? a. L Loseweight,eliminatejointmovement,and i h li i j i d stopsmoking b. Useassistivedevices,begin/maintainan exerciseregimen,andobtainimmunizations

ImproveFunction3,30
Rest Exercise Occupationalandphysicaltherapy Assistivedevices Assistive devices Weightloss Surgery

ReducingRisk3,30
Cardiovascularriskreduction o Smoking o Hypertension o Hyperlipidemia o Sedentarylifestyle Boneprotection Vaccines

RUAwakeforRA?
TrueorFalse:apatientdiagnosedwithRAmay useanNSAIDaloneoradiseasemodifyingagent (DMARD)aloneforlongtermcontroloftheir disease. disease a. True b. False

NSAIDs3
Placeintherapy o Symptomaticrelief o AdjuncttoDMARD No impact on disease progression Noimpactondiseaseprogression Maybeusedforsteroidsparingeffect

NSAIDCounseling3
Takewithfood Donotuseinlatepregnancy Monitorforandreport o Signs of bleeding Signsofbleeding o Signsofimpairedkidneyfunction o SignsofMIorstroke Reportothermedications

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Corticosteroids3,13
Placeintherapy o Bridgetherapy o Treatmentofacutesynovitis(flares) o TypicallynotusedinabsenceofDMARD g Adverseeventsassociatedwithlongtermuse Routes o Oral(taperasquicklyaspossibletolowesteffectivedose) o IMdepots(longerlasting) o Intraarticular(lesssystemiceffectsbutalsolocalrisks)

CorticosteroidCounseling3,13
Monitorforandreport: o Hypertension o Bloodglucose o Signsofinfection o Adrenocorticalinsufficiency(fatigue,weightloss,etc.) y( g , g , ) Takeoralproductwithfood EnsureadequateintakeofcalciumandvitaminD Informphysicianandpharmacistofothermedications

DecidingWhatDMARDtoStart11,12
1. DiseaseActivity(covered) 2. DiseaseDuration EarlyRA(<6months) EstablishedRA(> 6monthsormeeting1987ACRCriteria) g ( g) 3. FeaturesofPoorPrognosis(> 1ofthefollowing) Functionallimitation(e.g.,HAQorsimilar) Extraarticulardisease(e.g.,nodules,vasculitis,etc.) Positiverheumatoidfactor Positiveanticycliccitrullinatedpeptideantibodies Bonyerosionsbyradiograph

WhattoStartinEarlyRA12

RUAwakeforRA?
PatientEHhasbeendiagnosedwithRAoneweek ago.Diseaseactivityislow,andthereareno markersofpoorprognosis.Whattypeoftherapy wouldyourecommendtostart? would you recommend to start? a. TraditionalDMARDmonotherapy b. TraditionalDMARDcombotherapy c. AntiTNFtherapywithmethotrexate

TraditionalDMARDs3,12
Common
Methotrexate (MTX) Leflunomide (LEF) Sulfasalazine (SSZ) Hydroxychloroquine (HCQ)

Rare
Azathioprine Minocycline Cyclosporine Gold(IMorPO) Cyclophosphamide Penicillamine

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TraditionalDMARDOverview1417

TraditionalDMARDMOA/Kinetics1417
Inhibitspurinesynthesisandinflammatorycytokineproduction Onset:23weeks

MTX LEF SSZ HCQ

FirstusedforRAin1951,goldstandardoftraditionalDMARDs Lowcost,favorableefficacy,moststudiedDMARD

MTX LEF SSZ HCQ

AlternativetoMTXwhenMTXfailsorisintolerable L LesspotentialforlivertoxicitycomparedtoMTX,butmorecostly t ti l f li t i it d t MTX b t tl

Antiinflammatoryandantiproliferativeactivity O t 4 12 Onset:412weeks k

Anoptioninpatientswithalldiseasedurationsandactivitylevels MoreeffectiveandtolerablethanHCQ,similarefficacytoLEF

MOAunknown Onset:412weeks

Relativelysafe,acceptableforpatientswithlowdiseaseactivity Lacksmyelosuppressive,hepatic,andrenaltoxicities

MOAunknown Onset:atleast4weeks,failurenotconsideredfor6months

TraditionalDMARDDosing1417

TraditionalDMARDCI/Precautions1417
CI:pregnancyorpotentialpregnancy(orpartnerof),breastfeeding Precaution:renal,hepatic,orimmunedeficiency Precaution:manydrugdruginteractions

MTX LEF SSZ HCQ

Oral,IMorSubQ:7.515mgweekly,nottoexceed2025mg/week Doses>1517.5mgshouldbegivenIMorSubQ

MTX LEF SSZ HCQ

Oral:100mgdailyfor3daysthen1020mgdaily L di d Loadingdosenotrecommendedbyallpractitioners t d d b ll titi

CI:pregnancyorpotentialpregnancy(orpartnerof) , p , y Precaution:renal,hepatic,orimmunedeficiency Precaution:usewithwarfarin

Oral:5001,000mgdailyaftermealordividedBID Mayincreaseto1gBID,maxdose3g/day

CI:urinaryobstruction Precaution:pregnancy,breastfeeding Precaution:usewithwarfarinandantibiotics

Oral:400600mgdailytakenwithfood After13monthsmaydecreaseto200400mgdaily

CI:retinalorvisualchangesfromprior4aminoquinolonecompound CI:breastfeeding Precaution:psoriasispatients

TraditionalDMARDSideEffects1417

NamethatTraditionalDMARD
IampregnancycategoryX.Icanbedosedeither orallyorsubcutaneously.Whattraditional DMARDamI? a. Methotrexate b. Leflunomide

MTX LEF SSZ HCQ

NVD;1mgfolicaciddailytoreducestomatitis Myelosuppression,thrombocytopenia,leukopenia,hepatotoxicity

Elevatedliverenzymes(lesshepatotoxicthanMTX) M l Myelosuppression,gastrointestinalsideeffects,alopecia i t i t ti l id ff t l i

NVD;minimizedthroughdosetitrationanddosingwithfood Rash;minimizedthroughuseofcorticosteroids/antihistamines Colorchangesinurineand/orskin(yellow/orange)

Rash,diarrhea,photosensitivity Maculardamage,cornealtoxicity,retinopathy(eyeexamq912months)

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NamethatTraditionalDMARD
Igonicelywithameal,butbecarefulifyoure eatingthatmealoutsideinthesun.Youmight getalittleredwithoutsunblock. What traditionalDMARDamI? traditional DMARD am I? a. Sulfasalazine b. Hydroxychloroquine

NamethatTraditionalDMARD
UnlikemyfellowtraditionalDMARDs,Ihavenot beenknowntocausevisionchangesorurineor skincolorchanges.Myclosecousincanbedosed onceweekly,butIamlesslikelytocause once weekly but I am less likely to cause hepatotoxicity.Whattraditional DMARDamI? a. Leflunomide b. Hydroxychloroquine

TraditionalDMARDCounseling1417
Counseling Avoidpregnancy (women/partners) Takewithfood Hydrate andreport renaltoxicity Urine/skin discolorationmayoccur discoloration may occur Reportvisionchanges Maycausephotosensitivity Reportrashesimmediately Hepatictoxicity GItoxicity Hematologictoxicity X X X X X X X X X* X X X

BiologicDMARDs3,14,18
HCQ
X

MTX
X

LEF
X

SSZ
X X X

Effectiveinpatientsthatfailtraditionalagents OftencombinedwithMTX Greaterriskofbacterialinfections

o Tighterrestrictionsforcontraindicationstotherapy g py o Dosesmaybeheldifsignificantinfectionsdevelop o BaselineTBscreeningtoidentifylatentinfection

X X

BiologicDMARDsTimeline3,14,18
Year Medication Brand BiologicalTarget

TNF InhibitorsUseinRA3,14,18
TNF TNF IL1 TNF

1998 1999 2001 2002 2005 2006 2009 2009 2010

Etanercept Infliximab Anakinra Adalimumab Abatacept Rituximab Golimumab Certolizumab Tocilizumab

Enbrel Remicade Kineret Humira Orencia Rituxan Simponi Cimzia Actemra

CD80/CD86ofT cell CD20ofBcell TNF TNF IL6

TypicallyfirstbiologicDMARDused Historicallysimilarefficacies ACRrecommendationsdonotdifferentiate Switchingduetoaninadequateresponseor Switching due to an inadequate response or lossofefficacyisafeasibleoption Improvementscanoccurwithinweeks,but maytakeuptothreemonths

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TNF InhibitorsStructure&Dosing3,14,18
Medication Etanercept (Enbrel) Infliximab (Remicade) Adalimumab (Humira) Golimumab (Simponi) Certolizumab (Cimzia) ChemicalConstruct Dosing

RUAwakeforRA?
Whatcounselingpointsshouldthepharmacist providetoapatientreceivingaTNFblocker? a. Rotateinjectionsitesanduse a Rotate injection sites and use immediatelyafterremovingfrom thefridge b. Usegoodhygiene,washingyourhands regularlyandreportingsignsofinfectionas soonastheyoccur

Fusionprotein(2TNFreceptors linkedtohumanFcfragment) Murine/humanchimeric monoclonalantibody(MAb) FullyhumanMAb FullyhumanMAb PegylatedhumanizedFab fragment(noFcregion)

50mgSubQonceweeklyor 25mgtwiceweekly 3mg/kgIVonweeks0,2,6 andevery8weeks thereafter(withMTX) ( ) 40mgSubQ everyotherweek 50mgSubQoncemonthly (withMTX) 400mgsubQweeks0,2,4, then200mgevery2weeks or400mgevery4weeks

TNFAdverseEvents3,14,18,19
Headache Injectionsitereactions
o Erythema,edema,pruritis,pain o Lastafewdays,butfrequencydecreaseswithtime o Rotateinjectionsitesandallowtoreachroomtemperature

TNFAdverseEvents3,14,18,19
Myelosuppression(rare) Increasedriskofinfectionorreactivation
o URTIs,UTIs o Invasivefungalandotheropportunisticinfections o LatentTBandlatent/unrecognizedHBV /

Infusionreactions
o Fever,chills,pruritis,rash,nausea o Slowinfusionrate o PremedicatewithAPAP,NSAIDs,orcorticosteroids

Casereportsofdemyelinatingsyndromes Heartfailureexacerbation Malignancyriskcontroversial

Antiinfliximabantibodiesin721%ofpatients

Anakinra(Kineret)3,14,18

Abatacept(Orencia)3,14,18

MOA Dose PIT Onset ADEs

Interleukin1(IL1)receptorantagonist

MOA Dose

TcellcostimulationblockerviaCD80andCD86

100mgsubcutaneouslydaily(PFS) LessefficaciousthanantiTNFs UsuallyineffectiveinTNFnonresponders Onetothreemonths Injectionsitereactionsinupto80% Maylast24weeks,decreasingovertime

IV:5001000mgatweeks0,2,4,andevery4weeksafter SubQ:125mgonceweekly

PIT Onset

TypicallyreservedforTNFnonresponders Approximately50%ofTNFnonresponderswillrespond

Onetothreemonths

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AbataceptAdverseEvents3,14,18
Nausea(10%orgreater) Infection(URTI,nasopharyngitis) Infusionreactions(dizziness,HTN,headache) Hypersensitivity ExacerbationofCOPD

Rituximab(Rituxan)3,14,18

MOA Dose PIT Onset

DepletesBcellsbybindingtosurfaceCD20 Durationofeffectvaries,butcanlastseveralmonths Chimericmonoclonalantibody

Two1,000mgIVinfusionsseparatedbytwoweeks+MTX Retreatmentinrespondersmaybeconsideredafter> 4months

IndicatedforpatientsthatfailedoneormoreantiTNFtherapies

Typicallytwomonths

RituximabAdverseEvents3,14,18
Infusionreactions(upto35%ofpatients)
o Fever,chills,headache,nausea,cough,rash o IVmethylprednisolone30minutesprior o APAPorantihistaminesifneeded

Tocilizumab(Actemra)3,14,18

MOA Dose PIT Onset

InhibitsbindingofIL6toitsreceptors HumanizedMAb

Increasedriskofinfectionsorreactivationof infection,includingPML Antibodiesinupto6%aftersecondinfusion

4mg/kgIVinfusioneveryfourweeks May increase to 8 mg/kg based on response Mayincreaseto8mg/kgbasedonresponse Phase3Trial:162mgSubQonceweeklymetprimaryendpoint

IndicatedforpatientsthatfailedoneormoreantiTNFtherapies

Improvementmaybeseenwithinweeks Uptothreemonthsforfulleffect

TocilizumabAdverseEvents3,14,18
Infusionreactions Hyperlipidemia(increasedTC,HDL,LDL,TGL) Increasedliverenzymes Thrombocytopenia,neutropenia Thrombocytopenia neutropenia Increasedinfectionrisk Gastrointestinalperforation

NamethatBiologicDMARD
IamadministeredIV.Becauseyourbodymight developantibodiesagainstme,mydoseor frequencyofadministrationmayhaveto increase.WhatbiologicDMARDamI? increase What biologic DMARD am I? a. Infliximab(Remicade) b. Abatacept(Orencia)

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NamethatBiologicDMARD
IwasthefirstinmyclassandImstillvery populartoday.Iamusuallygivenonceweekly, buttheFDAapprovedmetobesplitupinto twiceweeklydoses.Whatbiologic twice weekly doses What biologic DMARDamI? a. Abatacept(Orencia) b. Etanercept(Enbrel)

NamethatBiologicDMARD
IprettydarngoodatwhatIdo;Iminaclassall alone.Ionlyhavetobegivenoncemonthly,but unfortunatelyIcanelevatecholesterollevels.If thingsgowell,I llsoonbeavailableasa things go well Ill soon be available as a onceweeklysubcutaneousinjection. WhatbiologicDMARDamI? a. Tocilizumab(Actemra) b. Adalimumab(Humira)

NamethatBiologicDMARD
Imstartedwithaloadingdoseof400mgat weeks0,2,and4soIcangettoworksooner. AfterthatIcanbegivenjustoncemonthly.Let patientsknowthatliketherestofmyclass, patients know that like the rest of my class Imaytakeupto3monthstoreachfull effectiveness.WhatbiologicDMARDamI? a. Certolizumabpegol(Cimzia) b. Golimumab(Simponi)

NamethatBiologicDMARD
YoullseemehelpingRApatientsquiteoften.Im a40mgsubcutaneousinjection,givenevery otherweek.Toavoidinjectionsitereactions, advisepatientstoallowmetoreachroom advise patients to allow me to reach room temperatureandtorotateinjectionsites. WhatbiologicDMARDamI? a. Etanercept(Enbrel) b. Adalimumab(Humira)

AssessingTherapyEfficacy20
ACRResponseRates
o ACR20(20%improvedtender/swollenjointcount) o ACR50(50%improvedtender/swollenjointcount) o ACR70(70%improvedtender/swollenjointcount)

ComparativeEfficacy2129
Drug Etanercept Infliximab Adalimumab Certolizumab Golimumab Anakinra Abatacept Rituximab Tocilizumab ACR20 65[71] [50] 54 [73] 46[59] [62] [34] 53[62] [51] [5156] ACR50 40[39] [27] 41 [62] 23[37] [40] [13] 16[32] [27] [2532] ACR70 21[15] [8] 26 [46] 6[21] [24] [3] 6[13] [12] [1113]

PlusXpercentimprovementin> 3:
o o o o o Patientsglobalassessment Physiciansglobalassessment Patientsassessmentofpain Degreeofdisability Levelofacutephasereactant

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BiologicDMARDCounseling2129
Maycauseheadacheorinjectionsitereactions Useaseptictechniquewhenadministering Allowsolutiontoreachroomtemperature Donotuseifdiscoloredorparticlespresent Do not use if discolored or particles present Rotateinjectionsites Donotrubtheinjectionsite Reportsignsofinfectionoranemia Avoidlivevaccineswhileontherapy

WhentoSwitch11
Inadequateresponseafter3months o TraditionalDMARDs o AntiTNFtherapies Inadequate response after 6 months Inadequateresponseafter6months o NonTNFbiologicDMARDs o Hydroxychloroquine? PleaseseeattachmentforcompleteACD treatmentalgorithmforestablishedRA

RAPipeline31
NumberofPipelineAgentsbyDiseaseState
900 800 700 600 500 400 300 200 100 0 774 789

RAPipeline31
Statusof RAPipeline Agents
NDAFiled,2 Undefined,4 Phase III,19 , PhaseI,27 Terminated,72 Approved,39

373 398 205 217 146 159 186 266 277

453

48

89

PhaseII,57 PreClinical,46

RAPipeline:PhaseIIIAgents31
11orallydosed 4largemolecule Agentsofinterest o Ixekizumab (subQ IL17 binder) Ixekizumab(subQ,IL 17binder) o Sarilumab(subQ,IL6inhibitor) o Fostamatinib(oral,sykkinaseinhibitor)

RAPipeline:AgentswithNDA31
Tofacitinib o Oral,5or10mgBID o Januskinaseinhibitor o Relatively high ACR response rates at 12 wks RelativelyhighACRresponseratesat12wks Ibuprofen+Famotidine

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PharmacistsRole3,30
Educationandcounseling o Roleoftherapyandexpectations o Natureofthedisease o Administration o Sideeffectmanagement,includinginfection o Nonpharmacologictherapies o Importanceofadherence Monitoringeffectiveness Providingorrecommendingvaccinations

References
Pleaserefertohandout.

Questions

Question1
1. Whichofthefollowingisfalseregardingrheumatoidarthritis(RA)? a. RAaffectsagreaterproportionofwomenthanmen. b. RAgenerallyaffectsjointsinasymmetricalmanner. c. RAoccursasaresultofafailureintheimmunesystem. d. AllpatientsdiagnosedwithRAwilldeveloprheumatoidfactor. e. Alloftheabovearetrue

Whatquestionsdoyouhave? What questions do you have?

Mike Crowe, PharmD Clinical Pharmacist Diplomat Specialty Pharmacy Keeping Patients Healthier...Longer. office: 810.768.9324 cell: 810.399.7589 fax: 810.282.0190 mcrowe@diplomatpharmacy.com diplomatpharmacy.com

Question2
2. WhichofthefollowingisnotadirecttargetofcurrentRAtherapy? a. TNFalpha b. Inflammatorycytokines c. Blymphocyteproliferation d. Tcellactivation e. AlloftheabovearetargetsofcurrentRAtherapy

Question3
3. OfthecounselingpointsbelowregardingprefilledsyringesofantiTNFagents,which wouldbetheleastappropriate? a. Itisrecommendedthatyouhavealcoholpads,cottonswabsandasharps containeratthetimeofinjection b. Toensureconsistency,shakethedevicewellpriortouse c. Toreduceinjectionsiteirritation,youmayallowthedevicetowarmfor1520 minutes d. Keeprefrigerated;donotfreezethecontentsofthedevice e. Keepingarecordofpreviouslyusedinjectionsitesmayhelpyouensurerotation ofsites

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Question4
4. Whichdrugandsideeffectcombinationbelowisappropriatelymatched? a. Leflunomide:visionchanges b. Hydroxychloroquine:elevatedliverenzymes c. Sulfasalazine:changesintheurineandskincolor d. Tocilizumab:reducedcholesterol e. Noneoftheabove

Question5
5. Whichcounselingpoint(s)shouldallpatientsreceiveregardingthebiologicagents? a. Rotateinjectionsites b. Donotinjectinareasoftheskinthataretender,red,bruisedorhard c. Themostcommonsideeffectisinjectionsitereaction d. Reportanysignsofinfectiontoyourphysician e. Alloftheabove

1987ACDDiagnosticCriteria

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MakeWayforRA:AnOverviewofRheumatoidArthritis References
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

MikeCrowe,Pharm.D.

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