Page 1of63 between this versionandtheVersionrecord. Pleasecitethis articleasdoi:10.1002/art.40149. through thecopyediting, typesetting, paginationandproofreadingprocess, whichmayleadtodifferences This istheauthormanuscript acceptedforpublicationandhasundergone full peerreviewbuthasnotbeen

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University of Alabama Birmingham, Universityat Medicine Alabama of Spondyloarthropathy Spondyloarthritis, Arthroplasty, lupus ery Systemic Adolph;Yates, University Pittsburgh of Arthritis &Rheumatology

thematosus (SLE) thematosus MBA MD Yates, MDYates, MD Dasa, Dasa, MD 3880Required 5517Words- 1 Linda Russell,Linda MD MD Susan M. Goodman,Susan M. MD for theManagementPerioperativefor ofAnti-rheumatic 2016 American2016 ofCollege Rheumatology/American Asso 1 12 9 , Elena , Losina, PhD Steve , Lee, DO 15 , LouisStryker, , MD , Jeremy Gililland, Jeremy , MD 5 17* , MichaelGeorge, , MD

Accepted Article 1 , Alexander , Sah,MD

Hospital forSpecial Hospital Surgery/Weill CornellMedicine 10 , Lisa , MD, A. Mandl, MPH 19 Undergoing Undergoing Elective or KneeTotal Hip Total Arthrop 13 1* , Ronald , MacKenzie, MD , Marat Marat Turgunbaev, , MD, MPH , , Springer, Bryan MD OrthoCarolina Hip OrthoCarolina and KneeCenter,Charlotte, NC This article isprotected by copyright. All rights reserved. 16 , Mark Goodman, Mark MD, University University of Pennsylvania,Philadelphia, PA Louisiana State Louisiana University, Orleans, New LA McMaster University,McMaster Hamilton, Ontario 6 , Ora Gewurz-Singer, Ora , MD University University of AnnMichigan, Arbor, MI Mayo Clinic, Mayo Rochester, MN 22 Arthritis &Rheumatology , Amy S.MillerAmy , John Wiley& Sons 1 2* , MichaelA.Mont, , MD , Gordon , Guyatt, MD 1 , Kaleb , Michaud, PhD 17 1 , Arlene Hurley-Rosenblatt, Arlene , ANP 14 Medication in PatientsRheumaticwith Diseases , Jasvinder A.Singh, Jasvinder , MBBS, MPH 14 , Barry Brause, Barry , MD 7 , Jon , Giles, T. MPH MD, ciation of Hip andciation ofHip Knee SurgeonsGuideline 4

3 11 , Matthew , Abdel, P. MD , New , York, NY 7 20,21 , Peter Sculco, Peter , MD

3

5 6

, Ted Mikuls, MSPHMikuls, MD, Ted , lasty 1 2 , Antonia , F.Chen, MD,

8 , Beverly Johnson, Beverly , 1 18

, Kyriakos Kirou, Kyriakos , 23* 1 , Scott , Sporer, , Adolph , 4 , Vinod , 20 , , Page 2of63 Page 3of63 project, as did as Singhproject, Drs. and co-senior as Yates, Goodman *Drs. andSpringer are investico-principal 2

Accepted Institute, Rothman ThomasJeffersonUniversity Hosp Article Dearborn-SahInstitute for Restoration, Joint Fremo National Data Bank National forRheumatic Data Diseases,Wichita, University of Alabama University at of Birmingham, Birmingham,AL University of Nebraska University of MedicalCenter,Omaha,NE University of Texas University of Medical Galveston,Branch, TX This article isprotected by copyright. All rights reserved. AmericanCollegeRheumatology, Atlanta, of GA Albert Einstein Albert College of Medicine,Bronx,NY Brigham andWomen’s Brigham Hospital, Boston, MA Midwest Orthopaedics Midwest at Rush, IL Chicago, University University of Pittsburgh, Pittsburgh,PA Rockefeller University,Rockefeller NYNew York, University of Utah, University Salt of City,UTLake ColumbiaUniversity, New NY York, Kaiser Fontana,Kaiser Permanente, CA Cleveland Cleveland Cleveland,Clinic, OH Arthritis &Rheumatology John Wiley& Sons investigators. 2 gators gators andcontributed equally guideline this to 11 10 ital,Philadelphia, PA

8 16 18

17

12 19 nt,CA

9

14

KS 13

20

23 21

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Keywords: goodm E-mail: Word(excludingcount references,acknowledgement): Fax: 212-472-6567 Phone: 212-606-1163 NY, York, 10021 support: Grant 3 biologic response biologic modifiers,prosthetic infection, spondyloarthritis, arthritis, inflammatory juvenile IRB approval: IRB Financial Conflict: andRheumatology (ACR) theAmericanAssociation of Correspondence: Committees notrequired. was society doesthat not guarantee, warrant,or endors American The College Rheumatology of is anindepend recommendationscannot adequately conveyalluncert recommendationsare not intended todictate payment warrantedby the evolution of medicalknowledge, te recommendationsdeveloped and endorsed by ACR the a desirable outcomesbut cannotguarantee any specifi circumstances. Guidelines andrecommendations are i regardingapplicationtheir be to made by physi the recommendations withinthis guideline tobe volunta todictate not the care of a particularpatient. Th Rheumatology are(ACR) intended toprovide guidance Guidelinesand recommendations developed and/or end hip Total arthroplasty, total kneearthroplasty,

This involvestudyhuman did not subjects and,the

Accepted This material the a is result projectof supporte Article Susan Goodman, Hospital MD, for Surgery/CSpecial Forms submitted required. as

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons arthritis, systemic lupus erythematosus, DMARDs, complications e ACR e considers adherence to the 3 cianin light of patient’seach individual e any e commercial product service. or HipandKnee Surgeons (AAHKS). c outcome. c Guidelinesand ry,with the ultimate determination chnology,and practice. ACR ntendedtopromote beneficial or TBD TBD for particular patterns of and practice ent, professional, ent, medicaland scientific aintiesand nuances patient of care. or insurance decisions. These orsed by orsed perioperative management,rheumatoid re subject re toperiodic revision as [email protected] dby the American College of refore,approval Human from Studies theAmerican Collegeof ornell, 535 E E New Street,ornell, 70th535

Page 4of63 Page 5of63 recommendations regardingrecommendations continue,to when when to glucocorticoidsinadults whoare undergoing electi disease-modifying traditional anti-rheumaticdrugs Results: and preferences. inpatient values the intervention,harms of consideri or versa, vice The surgeons. strength ofthe recommendation reflec usingconsensusgroupprocess a through convened a (GRADE) methodologywas ratetotheused quality of andandthe preferences, Grading Recommendations of perioperativemanagement inthe period. patientA p for synthesized continuing withholding vs. anti-rhe guideline.systematicmulti-stepA literature revie andmethodologists was convened to construct ke the Methods kneearthroplasty total (TKA). Objective ABSTRACT 4 idiopathic arthritis idiopathic (JIA), or lupussystemic eryth spondyloarthritis including(SpA), spond ankylosing perioperative anti-rheumatic managementof drug the Hip Association and of KneeSurgeons develo(AAHKS) The guideline The addresses perioperative the a use of : A panelArheumatologists, : of surgeons orthopaedic

Accepted Article This : collaborationbetweenAmerican the o College

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons ematosus(SLE)undergoing elective hip total (THA) wconducted,was then from which evidence was ngthe available quality of andthe evidence variab umaticdrug therapy andfor glucocorticoid optimal ve or RA,THATKA ve with SpA,JIA SLE.provides It or ylitis (AS) andylitispsoriatic(AS) arthritisjuvenile(PsA), (DMARDs),biologic agents, tofacitinib,and 4 anel was convened determineto patient values andthe evidence strength recommendations of ts the degreets the of certainty benefits that outweigh voting panelvotingrheumatologists of andorthopaedic ped an evidence-basedanped guideline forthe y clinical questionsclinical y answeredin be to the rapy foradults rapy rheumatoid with arthritis (RA), Assessment, andDevelopmentEvaluation withhold, and re-startto when these nti-rheumaticdrug therapy including specializingarthroplasty, inhip and knee fRheumatology (ACR) andthe American

or ility

Conclusion: allrecommendations, ofwhich conditional are andb medications, andthe perioperative optimal dosing o 5 conditionalrecommendations reflect paucity the of perioperativeanti-rheumatic medication management

Accepted Articleguideline This helpdecision-makingshould clin by

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons 5 highdirect quality randomized controlled dat trial f glucocorticoids.f The guideline includesseven ased on low on orased quality evidence. moderate at the time at of electiveTHA These or TKA. icians andicianspatients regarding a. Page 6of63 Page 7of63 inflammatory arthritis inflammatory (JIA), or lupussystemic ery improved quality improved the patientslife for rheu of with utilizationAlthoughthe wide ofdisease modifying INTRODUCTION improvementinpain andfunction afterTHA or TKA, arthroplasty (TKA)knee remainhigh (1-6). Patients 75% ofpatients 75% with SLE were immunosuppressive on biologics, patients on were were non-biologi 67% on with osteoarthritis with (OA). At the arthropla time of areand readmission reported higher forbe topatie ANDSIGNIFICANCE INNOVATIONS 6 • • • • •

patients rheumaticpatients with diseases. evidenc after andrestarted TKA and THA elective to to close as withheld be should medications Biologic rheumatic diseasesrheumaticare undergoing electivewho THA the throughout continued be may DMARDs Non-biologic an important important an opportunity to risk. mitigate anti-rheumaticmedication of management Appropriate ains ih huai dsae udron TA and jointinfection. periprosthetic THA undergoing diseases rheumatic with Patients hs udln i te is claoain f rheuma of collaboration first the is guideline This

Accepted Articlerecommendations formulate perioperative for the man

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology

John Wiley& Sons sty insty high-volume a orthopaedichospital, 46% of R thematosus(SLE), ratesof total andhiptota (THA) matoid arthritis matoid (RA), spondyloarthritis juv(SpA), anti-rheumaticdrugsand (DMARDs)biologics have withconditionsrheumatic significantreport ntsRA, with SpA, or SLE (7-10) compared patient to 6 c c DMARDs, and25% were corticosteroids, on while yet criticalyet such outcomes as infection,dislocatio medicationsand 15% on were corticosteroids. one dosing cycle as scheduling permits prior permits schedulingas cycle dosing one e of wound healing, typically 14 days, for all for days, 14 typically healing, wound of e andTKA. agement ofanti-rheumatic agement therapy. ooit ad rhpei sren to surgeons orthopaedic and tologists in the perioperative period may provide may period perioperative the in perioperative period in patients with patients in period perioperative K ae t nrae rs for risk increased at are TKA enile l A n, s Scope and target Scope and audience. preferences. setting,In this cliniciansrequire guidance regard opportunity an mitigate to (15-19). risk perioperative immunosuppressant managementof thera infection,as suchdisability overall anddisease a optimal The strategy to managethese is medications 7 psoriatic psoriatic arthritis SLE, (PSA), JIA,or und whoare guideline This pertains only adultpatientsto with when flare the medications are withheld. guidelinespotentialare the increasein infection biologicsreintroduction of the THA time at of or T knowledge, our thereare no randomized controlledt . Directtherapy. evidence, thathowever, address adult patients diagnosesadultpatients with SpA,ofJIA, RA, S or that open andthat informed communication between the pa clinical common situations, notapply butmay inal performingperioperativerisk assessmentand evalua intended is It by for use clinicians, including or procedures orthopaedic datauntil further are avail forTHA candidates or TKA. caution againstWe would This criteria. guideline is to forusedthose be wh

Accepted Article

This article isprotected by copyright. All rights reserved. This guideline This addresses anti-rheumatic medication Arthritis &Rheumatology John Wiley& Sons thopaedists,rheumatologists, and physiciansother ergoingelectiveTHATKA, andincorporates or patie ctivity/severity not be may modifiable,butthe opt ingperioperative anti-rheumatic management of drug o have elected o deemedandhave been appropriate riskadded the by medications riskvs. ofthe disea LE, but notLE, limited is those to who classifica meet RA, RA, SpAincluding Spondylitis (AS)Ankylosing and KA. relevant The outcomes considered forthese es perioperative es is management sparse To (20,21). l exceptionall unusual situations.or is It imperati able. 7 not known not Inherent(11-14). factors risk for tion, as patients.well as The guidelineaddresses rialsevaluating(RCTs) the cessation and extrapolationofthese guidelines to other tient, surgeontient, orthopaedic andrheumatologist py around py the arthroplasty time of present may managementinthose se ve ve imal tion nt

Page 8of63 Page 9of63 In place. takes addition, awhile is cost relevant 8 strong or conditional strong or (32). ofthe Much evidence wa recommendationUsing a GRADE, becan eitherin favo Supplementarypublication).before Appendix prese 1 disclosureswere managed ACRto according (i policy Table 1 Table project. this in our evaluation, inour and their intervals,dosing t as (http://www.rheumatology.org/Practice-Quality/Clini guideline This followed the guideline ACR developme MethodologyOverview METHODS perioperativeVTE bothprophylaxis;are covered in acute coronarymajor event(8,25),(MACE) guid this RA,patients with SpA,JIA, SLE beshould or assess managementofconcurrent disease,assuch that affe drugrheumatic therapy,choiceimplant, of surgical guideline This doesnotaddress indications forTHA relevant are guidelineformore this theyreflec as the quality availablethe of the anddeveloto evidence Recommendations Gradingof Assessment, Development evidence was lowevidence qualitymoderateto (33,34). stA containsthe populations included in guidelin this

Accepted Article

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons factor inhealthcare decisions,it notconside was hepanel determined dosingthat the intervaland ro t the t ofeffect. duration ed forrisk ed of venous thromboembolism (VTE)and pthe recommendations (30). Conflictsinterest of a or or TKA, decisionsmedicalunrelated anti- to approach, perioperative or evaluation and existing guidelines(26-29). rongrecommendationindicates that almost most or 8 s indirect, s coming non-surgical from anda studies, elinedoesnotaddress cardiacassessment risk or nsertherelink fulltoparticipant disclosurelist ctingrheumatoid the cervical spine.Although ntprocess nts the full the nts methods. cal-Support/Clinical-Practice-Guidelines),using th r or against or ther interventionproposed and either e (22-24). e andEvaluation (GRADE) methodologyrateto Table Table 2 contains drugs includedthe redin just ute nd ll e e SupplementaryAppendix high 3).Direct quality RCT glucocorticoids,what dose administered be should a Ifstopped?; 3. withheld, whentheybeshould resta be medications withheld prior to electiveTHA/TKA?; project where the plan was Thedefined. relevant t Voting Panel, the and LiteraturePanel, the Review Patient/Intervention/Comparator/Outcomesque(PICO) Core The Leadership Team drafted proj initially the Question DevelopmentPICO and Importance of Outcome andpreferences. values andJIA, RA ofall whom had THA undergone or TKA,r SupplementaryAppendix 2rosters). for team Additio SLEanexpert,patient expert, representatives, rhe finalrecommendations, consistingsu of orthopaedic Expert the Panel, whohelped theframe scope of the themembers), Literature ReviewTeam whoreviewed t those taking those versusnottaking medications i the of from representation both organizations.inclu This aproject This was collaboration between thean ACR InvolvedTeams but a action, minority mightnot (35,36). the inwhich majority the patientsinformed of woul patientsinformed all wouldrecommended choose the 9

Accepted Article

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons umatology methodologistsand GRADEexpert a (see nterest,comparing or the background risk of an THA ded a Core a ded forLeadership Team project (5 oversight Team fortheir Team review at face-to-face a meeting ect principles key scope, andrelevant clinical opics addressed included:opics Should 1. anti-rheumatic rtedaftersurgery?;In patients 4. using dfollow to choose recommended the course of 9 data available comparing the risk of orTHATKA in 2. theyare If withheld, when theybe should rgeons,rheumatologists, an infectiousdisease t time the of surgeryquestionslist (see of PICO i dparticipatingall AAHKS; teams included andthe project, Voting Panel,whodetermined the nally, a a nally, consisting Patient Panel adults11 of with eviewed evidence eviewed the and input provided on their action. Conditional action. recommendations are those he literatureand he compiledliterature the report, stions, whichstions, thenwere presentedtheto Expert s n

d Page 10of63 Page 11of63 Systematic Systematic Synthesisofthe Literature and Evidence outcome outcome alsodeemedwere relevant. states, coupled states, separately “arthroplasty;” with no theperiod time January for of 1September to 8, 20 resulted in resulted references total 2,230 Supplementa(see inused were PubMedand andkeyword/title/a Embase, PubMed andandCochraneLibrary; Emtreeterms for E controlled the thesauri vocabulary languageor for (mid-1960s+)from January 1, through1980, March 6, literatureSystematic performedsearcheswere in Em most critical most outcomes; outcomesother assuch hosp after year surgery)non-surgical infection, site (w determinedgroup The superficialthat both anddeep THA independentwith or TKA, of use of candidate me includinghospitalization, or infections, associate recommendations. the inform first asked,The “What inthe populationsTKA interest, sparse.of were To 10 not undergoing not surgery?”; secondasked, the i “What to guideline. the to Microsoft Excel usedMicrosoft was forabstracting data from RCTs, unablewe preparewereto GRADESummary of Fi Literature The Review analyzed Team andsynthesized literaturesearch results grouped by their wi match

Accepted Article

DistillerSRsoftware(available at: http://systemat

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons d withof each use of the drugscandidate inpatien ithin 90 daysithin surgery) 90 flareof anddisease th were randomized trials identifiedwere that relevan were address gap, this questions two includedwere to eachdatabase:Medical Subject Headings (MeSH) for th pertinent the questions. PICO 10 observationalstudies. When available, the evidence 16, using the inclusiveusing 16, searchthe the terms disease of ryA Appendix 5). final search wasupdate performed Processing sbackground the risk foradverse events associated italreadmission,and death, arthroplasty long-term base (1974+), thebase Cochrane Library and PubMed infection surgicalsite (reported withinfirst the isbackground the risk forserious adverse events search strategies2016. The developedwere using

dications in populationsdications the interest?” of data from from data studies. eligible lack Due the to of mbase (Supplementarymbase Appendix Text 4). words ndings (SoF) tablesndings formost (SoF) PICO questions. bstractinwords Cochrane the Library. Searches

ic-review.net/)used was screento the e e ts ts

t

(95% CI),number the (95% participants, andof the absol included summaries benefits the andharms for outco 11 The Patient The Panelattached greaterimportancefar t Movingfrom Evidenceto Recommendations considerations (includingbias).publication study limitations design of (including risk of the andimportant critical as outcome high, l moderate, drug-doseintherelationto last included. was recommendations For to withhold a medication, rec a unanimously.Insome instances, the combinedpanel Allrecommendations wereby supported ofover 80% t associated imprecision sample withsmall size. particularly duration, relevant instudies addressi infection risks from may THAmarkedly vary orTKA); came evidence from RCTs surgical outside of the con Considerations led that ratingto quality down of o notachieved was during initialanvote,the panel andanonymouslyan agreement defined80% the thresh both theircontext of clinical and experience i the Voting The Panel decideto met the finalrecommenda unablepreciselywereto quantify the difference in

Accepted Article

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bias),inconsistency, indirectness, an imprecision, ngglucocorticoid “stress-dose” andtherapy; nputthe from patient panel.The panel voted membersheldadditional discussions before re-votin f evidencef included indirectness (much ofthe value, noting it that was greaterthan 10:1. uteWeratedeffects. the evidence quality forof e 11 ow, or very ow, quality,low or taking account into oinfection the timeat than ofsurgery flares.to heterogeneity inbaseline medicationdoseand text, or from text, footor proceduresspine or inwhich PICO questions PICO into onefinal recommendation. mes ofacrossinterest mes studies, the relative effect

ommendation for ommendation suggested the surgery timing of tions. The discussedpaneltions. evidence the inthe he panel, andpanel,all he but supportedone were old for a recommendation;for a old 80%if agreement d other They ach g.

Page 12of63 Page 13of63 How toInterpret How theRecommendations THA or TKA, or THA (See Table TKA, 3). methotrexate,leflunomide, hydroxychloroquine, and/ SpAincludingRA, 1. andandASJIA, PsA, SLE, Non- Recommendations RESULTS/RECOMMENDATIONS 12 1. Allrecommendations inthis guideline are condi 1. 3. Therapies 3. that approvedafterwere the 2. For each recommendation, For summary a the suppo of 2. 4. PICO questions PICO combinedwere finalre inthe 4.

(see highlighted andbolded (see instatements provided. provided. recommendations arerecommendations guideline.madein this sensitivepreference andalways warrantshared a de but patients, not.some may Because this, condit of undesirable the so effects, courseaction the of wo desirablethat means the following effects of the r Acceptedincludedintheserecommendations. Article

This article isprotected by copyright. All rights reserved.

Arthritis &Rheumatology John Wiley& Sons 12 biologicDMARDs: Continue thecurrentdose of

original systematic literature systematic original review are not or sulfasalazineor patientsfor undergoing elective Table 3) Table commendationsforclarity. tional quality the todue the evidence of ecommendationprobably outweigh uld thetoapply majoritythe of . A. conditionalrecommendation ionalarerecommendations rtingconditions evidence or is cision-makingNoapproach. strong 8.87) and a higherand a 8.87) seriousadverse risk eventsof w risk forserious infection risk availableamong biologic (44-90). 2.54) systematicOur review did notprovid 2. SpAincludingRA, 2. andorASJIA, PsA, SLE:Withh [RR DMARDs (95%-1.10)] CI 0.06 was from0.0 low-qu surgery in after whothose continue DMARDs,andthe (41). andrecommendationTKA This based infe was on evidence indirect describing infectionlowrisk a w after infection risk orthopaedicsurgery when these (95%CI 0.17-0.91)(39,40).0.39 The base evidence is theinfections risk that decreasedof was infact w literature, included of that continuing RCTs of vs. conditionalrecommendation This was based low-to on 13 This medication(See Table 3). elective undergoing orTHA and TKA, planthe surger vs. control includingtreatmentvs. non-biologic DMARD) differences in risk differencesinrisk (44-90). literaturereview The literature that included literaturethat reviews systematic andmet performedwere inpatients undergoing THA or TKA. biologicsregarding infection inthe risk periopera patientsto important than inthe post-operaflares infections serious increased was biologics with wit

Acceptedrecommendationwas on based evidence was that rated Article

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons alsorevealed that the postoperative risk of infect discontinuing DMARDstime at the of surgery,revea tive tive untilfurther period andstudies clarify estab s (44-90). s avoidingAs infection significantly was ith continuingith DMARDshaving risk relative (RR) a o ith thesespecificith DMARDsinsettings than other TH h most ratiosodds/hazards/risk ~ 1.5(range, 0.61 ith most ratiosodds/hazards/risk ~ 1.5(range, 0.3 tivepanel period, the did notsupport separating e ample e that evidence would differential a support 13 drugs continued, becauseare risk bias. of Ther of oldbiologics all current prior patiesurgery toin rated down from high formoderatetoreduction in a-analysesbiologics of placebo vs. (andoccasional innon-surgicalpatients, that revealedrisk the o We abstracted We from data a review systematic of y at theatend ofthey dosing for that cycle specific

relative risk relative forflares continuing stopping vs. ality evidence (42,43).ality ction risk, although ction flares are alsoless frequent -moderatequality evidence. systematicA review down inquality for indirectness, no as RCTs lish ion ion more more nts nts 3 3 to f to e is e A led f ly ly Page 14of63 Page 15of63 those used forusedthe those treatment whichof RA, h usually and indirect were panel the consideredthese medica range a with from (95% CI 0.85 (98,105)0.62–1.17) surgery forthe surgery endthe of due cycle, dosing the to sothenephritis), recommendedpanel withholding th approved FDA although for inSLE notuse hasbeen s the approvedby U.S.Food Administrationand Drug ( with rituximab range with a fromwith ofRR to 0.66 0.73 events aftersurgery, events but nothere is approved role Observational reveal studies patients that sev with perioperativebenefit inSLE (100-102). DMARD) in DMARD) non-surgicalpatients rheumatoid with art meta-analysesrituximab placeboof vs. (andoccasio patientsIntoregard with SLE, a systematicreview intervalnadiratdosing the drug of effect.the more relevant indeterminingmore withholding the interv theto correspond duration immune-suppressan of the standard) the notand may associatedlow-do be with revealed that revealed infectionrisk biologics stronfor is notalways was Inreported. systematic a addition, increasedwere 1.3-fold, by andsepticemia ( 2-fold deep infectioncomplications deep by increased 1.5-fold aftercomplicationstotal joint arthroplasty (TJA) 14

Accepted Article

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons gly gly associatedwith high-dose therapy(higherdose was increased inpatients was RA towith a close 2-fold risk ofinfection and the paucity data supporti of ofliterature included that systematic reviews and for biologics these forpatients severeSLE with ere or active SLEere or aare at higher foradverse risk 8), medicationalthough use timeat the of surgery review, andnetwork meta-analysis meta-analysis (2,59);inSLE post-operative overall complications 14 (103,104), riskand a forall seriousadverse even averisk a ofinfection. notRituximab Moreover, is to RR = CI0.89 RR to (95% 0.7-1.14). However,data most nallyvs. control includingtreatment non-biologic alandtiming (92-95) the surgery at the ofendthe tudiedinmanifestations SLE (e.g.of severe lupus FDA)fortreatment ofSLE, and belimumab, tionsbeto similarinhibitors,TNFto similar to sebiologics(91), soserum not half-lifemay hritis and SLE revealed andhritisSLE ofthe seriousinfecti risk ese ese medications prior surgeryto andplanning the

t effect. Theeffect. dosingt was cycle therefore chosenas nd ng than ts ts

ons ons

(97). Although (97). drug this has extremelyan shortse rate (IR) 2.91 rate (95%2.27-3.74) CI (96) andhigher r surgicalpatients showing riskthat the serious of placebo tofacitinibvs. (and occasionallyvs. contr recommendation This was indirect on based evidence undergoing patients with or THA 3).TKA (See Table immunosuppressionafterthe drugwithheld is except includingrisk perioperative SLE mitigation. manif 15 value patients value SLE wouldwith flares, on place whic reluctantthey were to SLE voteon medication manag 3. SpARA, 3. including JIA:andASor WithholdPsA, every weeks,given would 4 their schedule surgery d afterthe week first during withhelddose 7. month treated 9. rituximabPatients with every 6 months dosed every 8 weeks, wouldtheir schedule surgery i wouldintervals, plan their during surgery week thr example, usingFor guideline, this patients treated risk. direct evidence, however,direct linking perioperativeinf forbelimumab indications andare (102,106), notth recommendation the interval(92-95).dosing on The immunologic the drugseffects differs of these from known about associationknown the ofsurgical risk with b

Accepted Article

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons olincludingtreatment non-biologic inDMARDs)non- infections increased was tofacitinib with inci with iskofinfectionsall RR ofwith 5.7(95% CI 1.8-18 estationsandrash synovitis, of the commonare cli withadalimumab,dosedroutinely at 2-week ection riskection theto these use of andbiologics,litt rumlittlehalf-life, is knownabout the duration o iologics foriologicspatients SLE. with duration the Since ee,patients while withtreated infliximab, when h be might organ threatening, compared infectionto wouldtheir schedule surgery possible inthewhen 15 Patients with Patients SLE receivingbelimumab, iswhich tofacitinib for atfor tofacitinib days least 7 to prior surgeryin the level,serum the basedpanel the ought to increase oughtto perioperative risk. Thereis no uring5. week n week afterthe the first during withhelddose wee

patient panel didpanel notincludepatient SLE,patients with an for indirect translationalfor data suggestshost that

ementstrategies they as aboutunclear were the from systematic from reviews and meta-analyses of .1) le is dence of of f

nical

d k k

Page 16of63 Page 17of63 These These medicationsbecan week withheld prior one to not-severepatients with SLE, forwhom the morbidit the monitoring patient of aftersurgery permi would there is while knowninfectionrisk a associated wi patients withFor not-severe SLE, the course time t TKA (See Table 3). azathioprine, azathioprine, cyclosporine,tacrolimus,or one week SLENot-severe 5. (as defined Withho Table in 1)*: individual patient’swith basis rheumatologist. the feltpanel that the decisions regarding electivesu 4. (44,50,51,54,80,82,96,99).grows ofwithholding duration inchange may future, the a returns normaltodefense days. 7 at Therefore,the 16 There is muchThere uncertainty published andexpelittle TKA (See Table 3). azathioprine mofetil, , cyclosporine,tacrolimusor medication medication managementin severepatients SLE. with azathioprine, cyclosporine, azathioprine, tacrolimus or s through recommendation the continueto current dosethe of may be different be from may the flaretime afterSLE to w is that analogy the course time rejectionof organ patientstransplant whocontinue anti-rejection the

Accepted ArticleSevereSLE* (as defined Table in 1): Continuethe c

This article isprotected by copyright. All rights reserved.

Arthritis &Rheumatology John Wiley& Sons rgery severeinpatients with SLE be should madeon afterimmunosuppressantwithholding medication

th theseth panelmedications. The felt that careful o flares after o withholding is medications notknown ithholdingmedications. These led considerations to through allpatientssurgery in undergoing orTHA urgeryinall patients with Neverthelessevere SLE. 16 rienceregarding risks associatedperioperativ with rapysurgerythrough (107,108); the caveat this to panel recognized recommendationthat the forthe ldthecurrentdose ofmycophenolate mofetil, s physician s andpatient experience drug this with tre-starting the clinicaltomedications prior fla yinfection of might outweighrisk flare.ofthe a prior to allprior patientssurgery in undergoing orTHA

There is, however,There indirect with evidence organ surgery, permitting surgery, somereturn ofnormal

methotrexate, mycophenolate mofetil, urrent dose ofurrent methotrexate, mycophenolate res in res s, s, an e e , ,

perioperativeglucocorticoid dosing. Hemodynamic instability/hypotension Hemodynamic andinfection r (Seedosing”) Table 3). rather TKA, thanadministeringperioperative supra- patients arewho with, receiving foglucocorticoids SpAincludingRA, 7. SLE:andASor PsA, Continuet of use activeanwarn with infection in or high-ris or drainage, or andnothere is clinical n evidence of regardingrestart the time optimal to af medication healing (normally healing (normally about 14all days), sutures/stapl by days.reached 14 Therefore,biologic therapy can andjudgmentclinical forabsence surgical of andn The decisionrestart to The anti-rheumatic therapy can and drainage, nothere evidenceis clinical ofnon- about days),(normally 14 sutures/staples all o are wastherapy prior withheld undergoingto or TKA THA function, immune andrestarted at days3-5 aftersu 17 6 (109,110).and reversal signaling,theand blocking novo de pathway puri of suppression these includingwith medications, leuko infection theor surgicalat elsewhere. Thesite or .

Accepted ArticleSpARA, including andASJIA SLE: or PsA, b Restart

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Arthritis &Rheumatology John Wiley& Sons k settings, k with as suchan open wound. re re aremultiple postulated mechanisms forimmune on-surgicalinfections. site noThere is direct evi esare noout,there is significant swelling, eryth on-surgicalinfections; site wound is typic closure surgical site infections surgical (SeeTable 3). be on based evaluation of the statupatient’s wound 17 ter but surgery, standardprecautionsfor biologics ut,noisthere significant swelling,erythema or newithsynthesis, different time forcourses onset r r theirrheumatic conditionandor undergoing THA hecurrentdosedaily of glucocorticoids adult in rgeryin absence the of woundhealing complications be re-started be theonce wound evidenceshows of penia,interference with t-cell co-stimulatory physiologic glucocorticoidphysiologic “stress(so-called doses iskwere specific two areas concernin of toregard

iologic iologic therapy patients biologic in whom for oncethe ofwoundhealing showsevidence

dence ema ally ally

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Page 18of63 Page 19of63 increase ininfection increase risk forTJAfollowingusers associated the administrationwith oflive vaccines Control Disease (CDC) prednisone/day was mg 20 f of Regarding the infection Regardingthe panelrisk, the notedthat (111). the usualdaily the doserather dose” inl “stress than glucocorticoiddoseprior surgeryto underto 20 mg patientoptimizing forthe elective THA andTKA sho perioperativeperiod. Included recommendations addr undergoingadults elective designedand THATKA was ACR/AAHKS2016 guidelineThe forthe perioperative DISCUSSION patients given theirpatients currentglucocorticoid daily d review suggestedsystematic there nothat signi was dueand imprecision smallto numbers) andevidence (rated down forindirectness (rated todue glucoco varying treating primary for adrenal prima insufficiency or glucocorticoids received in during childhood develo condition;rheumaticdoes it not refer patientsto RA, AS, PsA,AS, SLE,RA, whoare or receivingglucocortico perioperativesupra-physiologic glucocorticoid dose glucocorticoidsinadultpatients whoare receiving Regardinginstability, hemodynamic recommendati the 18

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This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons of chronic glucocorticoids of above Therefomg/day. 15 ightthe effect infection of on risk (110,111). ose comparedose thoseto receiving steroi“stress-dose receivingglucocorticoidsfor JIA have who may the the cut-offforimmunosuppression per Centers the f ryhypothalamic disease. Low-quality RCT evidence . In. addition, observationalstudies demonstrate an glucocorticoids,rather administeringthan ids (≤16 prednisone mg/day orequivalent)for their 18 pment, or to those patientsorpment,those to receivingglucocorticoi /dayprednisone equivalent, or andadministering uldinclude,when possible, minimizingdaily the rticoiddoses, heterogeneity surgical procedures of s (“stressdosing”), s specificallyrefersadultsto ficanthemodynamic difference between those or at least2 or weeks, inthe context risk of managementofanti-rheumatic drug therapy for from observational from summarized trials in a

for use byfor cliniciansand patients in the ess the anti-rheumatic use ess of drug therapy on to continueto on current the dose daily of

with re, ds”

ds or , , includingJIA ,orAS andrecognizing PsA, SLE, that includingtofacitinib, DMARDs, andbiologics,gluco 19 This project brought project This together major stakeholders – foreach evidence recommendation. transparent been regarding the strengthboth ofthe risks. mitigate Wehave used GRADEmethodology s to The population. optimal managementofanti-rheumati THA andrates of or TKA of infection andadverse ev anti-rheumatic medications inthe perioperativeTJA noto consensus little among surgeons orthopaedic o managementofthese high-risk patients through gr a methodologistsandpatients – a create to patient-c A major limitation major inA guideline this the is paucity forphysicians making and alike. patients andinfectionperioperative risk of and flare. The infection). any withholding medicationsevidenceinwhich from flarethan important risk, and drove direc this the andagreement evidence among stakeholders.pati The DMARDswhile and biologics, on we sought fulfillto recommendations.Nonetheless, patients as rheu with quality the of evidence wasconsideredlow, l which

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This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons ofhigh-quality, direct evidence regardingmedicat indirectnature the evidence of the reaprimary was anti-rheumatic medication use is at frequent the t tionthe recommendations of (uniformly infavor of corticoids for adultcorticoids patient the RA, with SpA, 19 entric,expert-led determinetogroup optimal ed to a ed conditionaldesignation to all for the thefor guidance need based the beston available ents, including ents, readmission, are increased in this orthopaedicarthroplasty surgeons, rheumatologists, period, leads which to often uncertaintyindecisi recommendation andthe limited quality of the oup consensus process.oup consensus date,To therehas been r rheumatologistsr on the optimal toway manage non-operativepopulations increasein suggested

matic diseasesfrequently matic undergo andTHA TKA ynthesize best ynthesize availablethe evidence andhave c toc medications thesetreatdiseases may ent panel ent infection thought risk was much more ions ime son on on

Page 20of63 Page 21of63 inpersonevaluated prior restartingto biologics. smartphone or mobileother health technologies; thi nurse visiting services, as takingwell as photogra within surgeon 2 weeks of screeningdischarge, mech thereareinfection. While differencesinpractice as suchTopics risk, cardiac venous deep thrombosis 20 a minimum of minimum a of days)14 and judgmentclinical forthe recommendation The biologicsrestartto was based o forSLE needed patients. stakeholders rheumatology strongly felt that periop patientslack ofour SLE patienton panelthe a was patientsIntoregard with SLE, the recognizepanel anddiseases, category with exception the SLE. of however, evidence, on each individual medication an Anti-rheumaticmedications anddisease states were perioperative anti-rheumatic managementof drug the are undergoing who The orguidelineTHATKA. li was and care of the andcervicalcare of spine related are theto p flares flares be threatening,may organ patients andSLE m multiple by involvement, as organ complexwell as o managementcomplexfor a disease assuch SLE would

Accepted Article

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phs ofavailablethe forwound review by e-mail, patternsandpatientsmany do return theirtonot erioperative careerioperative patients with of diseasrheumatic dthat recommendations forperioperative medication limitation. Nonetheless, the and orthopaedic 20 erativemedication managementguidance was risk, risk re-admissions,of 90-day and management absence both surgicalsite of andnon-surgical sit ayaverse be more infection, risk to then of flare r unusualregimens. medication SLEMoreover, s s help would identifyto those whoshould be mited, however, mited, risksto attributable to initiallyevaluated individually.lack Due a to of d disease state, ddisease the medications combinedwere by anisms to anisms assessto the wound includeutilizing

n the patient’s nthe healing requiringwound (generally rapy. rapy. be challenging,SLE be as is frequently complicated e e so e e

anti-rheumaticdrugs intheleading uptime to elec guidelineInsummary, this cliniciansandprovides preparephysicians forTHA andTKA. optimization, optimization, anddoesnot discussion a preclude of clinical scenarios arescenariosclinical addressed. guideline This do potentialall not perioperativeclinical scenarios guidanceregardingand discussion medication manage recommendations The that this form guideline are no study design.the perioperative managementandregimensinclude asses numbers patients. small of RCTsshould Multicenter reflects surgery older,lower, regimensdosing for controlled trials controlled defineto the optimal medication registriesbiologicsthrough andadministrative dat of dose, diagnosis,dose, andof surgical procedureleaves u current glucocorticoid current dose rather “stressthan dos andrecommended topics theybe targetedforfuture part conducted as collaborationof a between the tw Voting The Panelfelt it worthwhilesuggestto re a 21 3. 3. 2. 2. 1. 1. Perioperativemanagement ofDMARDs Perioperativemanagement ofbiologics

Accepted ArticlePerioperativeglucocorticoid management

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons are are this coveredby guideline,but common the most esnotreplace perioperative clinical assessmentan methotrexate,andstudies forleflunomide include managementstrategy. searchroadmapforfuture studies thatbe could patientswith a workingdocument on howto manage abases,as planningwell as multicenter randomized s with s onlylow-quality evidence. .Thesuggested Voting investigationPanel exis of tiveandTHArecommendationsTKA. The provide : : Currently, for from patients data RCTs undergoing ing,”limitednumbers patients of andheterogeneity 21 risks andbenefits surgeryto patients as andthei beperformed determineto optimal the o o organizations. team The thediscussed following ttreatment butcanmandates, providetoused be research:

. . RCTWhile supports data the continuing the ment priorment surgery.to The authors recognize that sment of co-morbidities sment of and inglucocorticoid use d r ting

Page 22of63 Page 23of63 joint arthroplasty recipientsjoint United inthe States and performing the literature andperformingthe search andupdates, a Hicks, Jennifer Hicks, Kangal, Marna McDermott, TiffanyAn project Acompora,Katie this – Deserae Constantinea patient assistanceinvolvementwith in guideli this Expert Panel. theWe thank Foundation Arthritis and Hochberg, MPH, MD, Eric and MD, Matteson, WilliamB thank AnneBass,We MD, Berbari, Elie MD, MarkFigg ACKNOWLEDGMENTS foundation forthe future research. and preferences. patient values The acknowledgement manuscript preparation. manuscript We thank Janet Ms. Waters f andmeetingcoordinating theadministrative aspects thank theWe staff, ACR including Regina Ms. Parker 2. Ravi B, CroxfordRavi B, 2. Reichmann R, WM, E, Losina Katz drugs:antirheumatic evidence from randomizedcontr SinghStrandV, 1. JA. Improved health-related qual REFERENCES strategy. search 2014;41(5):867-74. among increased patientsUS with lupussystemic ery Mertelsmann-Voss 3. C, Lyman S, TJ, Pan Goodman S, Rheumatol 2012;26(5):637-47. guidance important that wasbyinformed the availab 22

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This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons andfrom Ontario 2007.to2001 ResBestClinPract ne ne as patientsproject, well the whoparticipated i itylife withof disease-modifyingeffective 22 nd Ms. Janet ndMs. Joyce forpeer-reviewing the literatur for assistancein face-to-faceorganizing the JN, HawkerTheGA. changing demographicstotal of Healthythe Global Living Foundation fortheir project, ofthe and Robin Ms. forassistance Lane u, Marshall Marshall u, Davis, Franklin- Laureen Nancy Fable, nOhlin,Jodi Pound, Kirsten and Smith, Voigh Kelly thematosus:1991-2005. J Rheumatol leliterature, expertiseclinical andexperience, a

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This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons ipknee replacement inpatients or rheumatoid with l sitel infection reportingandrisk stratification. rheumatoid arthritis. Arthritis Rheumatol heumatoidarthritis, juvenileidiopathic arthritis, alkneereplacement compared patients withwith necrosisfactor inpatients with arthritrheumatoid tal tal kneearthroplasty: a retrospective case-control och E, KrederH,och E, et Increasedal. complicat risk of ndfunction poor hipafter total replacementsthan 23 TsarasHanssen G, AD, etTheal. Mayoprosthetic 432-9. 2011, but2011, large-joint replacement ratesremain ):1774-80. MP, Fein AW,Fein MP, al. et Patients systemic with lupus enceofknee and hip joint total replacement in J, J, Dixey P,etKiely Handal. surgery andr foot L. L. outcomesAdverse after surgery inpatientsmajor is after hipis after or knee arthroplasty:cohort a study. Bamlet WR,Crowson CS, andet risk Incidence al. n of improved long-term nof outcomesofrheumatoid erseevents hipafter total arthroplasty. J rthritis Rheumatol rthritis 2014;66(5):1081-9.

ttnerF, YY,et Lee Rheumatoidal. arthritis doesn ulation-based study. ulation-based Ann Rheum Dis ;40(5):617-23. toidarthritis associated is higher with ninety-day Figgie Mandl MP, US LA. inrates trends of ,Demmer RT, Mandl LA.and Patterns iggie Alexiades MP, etal. MM, Patients with Figgieet al. M, Patientsrheumatoid with Infect and ates ions is is

ot

Page 24of63 Page 25of63 20. SM, 20. Kurtz Lau Watson E, Schmier H,JK, Parvizi Arthritisarthritis. Rheum2002;46(9):2294-300. MF,19. Doran Crowson CS, PondGR, WM, O'Fallon Gab 91. Rhythm Society,SocietyRhythm of AnesthesiCardiovascular AmericanSocietyGuidelines, Echocardiography, of A American 26. CollegeCardiology of Foundation/Ameri erythematosus.Am JMed 2008;121(10Suppl 1):S3-8. Salmon Roman25. JE, Subclinical MJ. atherosclerosi 2005;64(4):524-7. Fernando 24. Isenberg MM, Howto DA. monitorSLE in in contraceptives women systemic with lupus erythem M,Kim 23. Petri KalunianMY, Grossman HahnJ,KC, randomized Anntrial. Intern Med. 2005;142(12 1) Pt andprogesteronehormone replacement therapy on dis BuyonJP, 22. MA, Petri Kim KalunianMY, KC, Grossm Recommendations Advisory of the Committee Immuni on Centers 21. forDisease and Control Gen Prevention. United the States.J Arthroplasty Suppl):2012;27(8 College ofCollegeChest Physicians Evidence-Based Clinical surgery orthopedic patients: Antithrombotic Therapy with an increasedan riskwith infection of inpatients wit 28. Falck-Ytter 28. Francis Y, CW,Johanson NA,Curley Circulation 2009;120(21):e169-276. ofcardiology college foundation/American heart ass perioperativecardiovascular and evaluation fo care update focused perioperative on beta incorblockade Fleisher 27. Beckman JA,LA, BrownKA, H, Calkins C JAm Collsurgery. Cardiol 2009;54(22):e13-e118. ACC/AHA the guidelines2007 on perioperative cardio Interventions,etACCF/AHA2009al. focusedupdate 18. Au ReedG, 18. JR,K, Curtis JM, Greenberg Kremer J and review meta-analysis. Rheumatology (Oxford) 201 patients undergoing patients electivehip andknee arthropla OrthopaedicSurgeons clinical practiceguideline on Jacobs JJ, 29. MA, BozicMont DellaValle KJ, G CJ, 325S. alphafactor inhibitorsnecrosis in rheumatoid arth Goodman SM, 17. I,Menon Christos Smethurst PJ, R, 24

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This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons hrheumatoid arthritis. Ann RheumDis 2011;70(5):78 oodman SB, CG,oodman Lewis etAmericanal. Academy of J.Economic burden jointof periprosthetic infectio ritisundergoing patients arthroplasty: a systemati 61-5.e1. C, OE,S, SchulmanDahl etal. PreventionVTE in of Practice Guidelines.Chest Suppl):e278S 2012;141(2 24 : preventing : thromboembolic venous disease in haikof EL, Fleischmann haikof EL, KE,et ACCF/AHA2009al. r surgery: noncardiac report a American ofthe D, D, etStrandHighal.V, disease activityassoci is s in s arthritisrheumatoid and lupussystemic sty.Joint Surg JBone Am 2012;94(8):746-7. ologists, Society ologists, forCardiovascular Angiographyan eralRecommendations Immunization: on ociation task force ociation task practiceguidelines. on BH,SammaritanoLR, et Combinedal. oral :953-62. merican Societymerican ofNuclear Heart Cardiology, onperioperativebeta blockade incorporated into poratedACC/AHA into the guidelines2007 on andPreventionThrombosis, Americanof 9th ed: an J, HahnJ,an BH. combinedeffect The of estrogen Bykerk VP. ManagementBykerk ofperioperativetumour vascularevaluation noncardiac andcare for

can Heart Association Heart can Task on Force Practice

6;55(3):573-82. atosus.NEnglJ Med. 2005;353(24):2550-8. routine routine practice.clinical Ann Rheum Dis. riel SE. PredictorsSE. infection riel of inrheumatoid ease activity in ease systemic lupus a erythematosus: zation Practices. MMWRzation 2011;60(RR- 2):22-23. ated ated c nin

5- - d in RA patientsin RA undergoing Arthritis. arthroplasty 43. Goodman SM, Friedlander 43. FiggieC, R, A, Hoang A 2001;60(3):214-7. rheumatoidpatients with arthritis undergoing elect Grennan Gray42. J,DM, Loudon S. Fear J, Methotrex treating rheumatoid for arthritis. CochraneDatabas 41. Lopez-Olivo Siddhanamatha HR, MA, B,Shea Tugwe rheumatoid with arthritis. JClinRheumatol. 2003;9 treatmentleflunomide on theinfectiou incidence of SakahashiN, 40. Tanaka E,H, Hirose Sato Ishima K, 2001;60(3):214-7. rheumatoidpatients with arthritis undergoing elect Grennan Gray39. J,DM, Loudon S. Fear J, Methotrex information elicittoBMJ preferences. Open 2014;4( interview-based structured combined study withra a thepreferences expected of hipefficacy arthros of Zhang Y, Tikkinen38. KA, Agoritsas Ayeni OR,T, Ale Expect Health 2015;18(6):2318-27. antithrombotic for oral therapy inpatients with at Alonso-Coello 37. P, MontoriVM, Diaz MG, Devereaux JClinEpidemiolstrength. 2013;66(7):726-35. Going from 15. evidence to recommendation-determina Andrews SchunemannJC, 36. HJ,AD,Oxman K, Pottie 2013;66(7):719-25.Epidemiol from Going evidence recommendations:to the signifi Andrews GuyattJ, 35. G, AD,Oxman Alderson P, Dahm JClinEpidemiol 2016;72:45-55. interpretto professionals and recommendations use Neumann SantessoI, 34. N, EA, Akl Vandvik Rind DM, healthcare Clinicalchoices. practice2: guidelines toEvidence (EtD) Decision systematicframeworks: a Alonso-Coello 33. P, Oxman AD, BrignardelJ, Moberg recommendations.BMJ 2008;336(7652):1049-51. Guyatt Oxman32. GH, AD, Falck-YtterVis Kunz R, Y, evidence”anditwhy is important clinicians?.to B Guyatt Oxman31. GH, AD, Vist Falck-Ytt Kunz R, GE, rating consensus on quality andof strengt evidence Guyatt Oxman30. GH, AD, GE, Falck-Ytt Vist KunzR, 25

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This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons . BMJ. 2016;353:i2089. Rheumatol.2015;67(suppl 10). MJ MJ 2008;336(7651):995-8. rial physician fibrillation: andpatient perspectiv copyforosteoarthritis: a forprotocol a multinati T, Ishii S. Examination risk of ofthe continuous 25 (2):115-8. xander P, Imamxander P, al. M, and et Patients’ values ive orthopaedic Ann surgery. Rheum Dis. ive orthopaedic Ann surgery. Rheum Dis. h ofrecommendations.BMJ 2008;336(7650):924-6. t GE, Liberatit A,al. fromet Going evidence to eSystRev. 2014;(6):CD000957. er Schunemanner Y, HJ,et Whatal. is “quality of Alonso-Coelloer Y, et GRADE:al. emerginganP, s complications s after jointarthroplasty inpatient 10):e005536. and approach transparent to informed making well ndersen K,ndersen Pernisal. AB, occurfrequentlet Flares ateandearly postoperative incomplications ateandearly postoperative incomplications ndomisedsurvey on the amount optimal of lo-PetersenR,EA, Akl Davoli al. M, et GRADE inguidelinesdeveloped GRADEapproach.with the PO, Alonso-Coello PO, P,et al. health guideAfor canceandpresentation recommendations. of JClin

Meerpohl JJ,Coello Meerpohl et PA, GRADEal.guidelines: PJ, Mas G, PJ, Diez etMas AI,Valuesal. andpreferences P, Falck-Ytter Y, P, etGRADEal.guidelines: 14. ll P,Suarez-AlmazorllWells GA, ME. Methotrexate nts of recommendation’sof a nts directionand es. onal onal s s y y Page 26of63 Page 27of63 factor inhibitors ininhibitors factor arthritis:rheumatoid a meta-a TL,Rho52. Michaud YH, Shamliyan T, ChoiKM,Kuntz rheumatoidpatients with arthritis. Arthritis Rheum 55. A, 55. Lethaby Lopez-Olivo L,MA, A, Burls Maxwell 2013;14:298. oftreatmentrheumatoid arthritis:a systematic rev He Y, Chan54. Wong AY, EW,Lau WC, Man, KK,Chui C 28. lupussystemic erythematosus treatment: systematic Borba HH, A,53. Wiens de TT,C.,SouzaCorrer Pont 32. infectionsandall-cause inphase mortality phaII, Cohen S, 51. Radominski SC, Gomez-Reino JJ,L,Wang randomized controlledtrials. JInternKorean Med. responseinadequate to ormethotrexatedisease-modi Song, SC,GG, 50. Bae Lee YH.andEfficacy safety o 2014;(9):CD007649. pegolCertolizumab (CDP870) forrheumatoid arthriti RuizGarcia V,49. Jobanputra CabelloP, A,J Burls arthritis.rheumatoid Cochrane SystDatabase 2 Rev. 48. Lopez-Olivo Amezaga MA, Urruela M, McGahan L, P Rheumatol. 2015;25:672-8. Strand Ahadieh44. FrenchV, S, GeierJ,KrishnaJ, 26 patients rheumatoidpatients with arthritis usingbiologic a 47. ItoH, Kojima47. M,Nishida K, KojimMatsushitaI, forinhibitorsankylosing spondylitis. Cochrane Dat 46. Maxwell Zochling LJ, J, SinghA, Boonen JA,Ver Lancet. analysis. 2015;386:258-65. in infection biologicaltreatment ofpatients with Singh JA,Cameron 45. C, NoorbaloochiCullisS, T, intreatmentrheumatoid arthritis clinical trials. seriousinfections analysis of tofacitinib with and Chinese population. Chinese JEur OrthopSurg Traumatol. 20 of randomized, of double-blind, placebo-controlled cli ZhangZH, 57. Li J,Wang Y, ShiZJ.intheEtanercept ankylosing of spondylitiswith blockers:TNF a meta MA,56. Machado Barbosa Almeida AraujoAM,MM, de V arthritis.rheumatoid Cochrane SystDatabase 2 Rev.

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This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons Arthritis Res Ther. 2015;17:362. biologicdisease-modifying antirheumatic drug seIII, extensionand long-term studies of tofaciti rheumatoidarthritis:a systematic review and meta- B,Vela Casasempere Bort-Marti P, etS,al. swami S, swami S,Systematical. Menon et review and meta nalysisupdate Amof Jtrials. 44 Med. 2014; 127:12 TuckerChristensen , M al. R, serious et Risk of alsystematicA- agent review and meta-analysis. M a a T, Nakayama et al. T, complications Postoperative abaseSystRev. 2015;(4):CD005468. f tofacitinibrheumatoidfor active arthritis with as Tanjong MM, Ghogomu TNF-alphaal. E, et 2014;29:656-63. -analysis.Rheumatol Int. 2013;33:2199-213. atol.2014;66:2924-37. iewand BMC meta-analysis. Musculoskelet Disord. 26 TugwellWells GA. P, Etanercept treatment for the o nical trials, and trials, nicalcomparison thethe Caucasian of a treatmentankylosing spondylitis: of a meta-analysi aroloEfficacy R. and safety ofbiologictherapies 015;1:CD007356. 013;(5)CD004525. 13;23:497-506. s in s adults.Cochrane Database SystRev. comparative The HK. safety necrosis of tumor reviewand meta-analysis. BioDrugs. 2014;28:211- Krishnaswami S,Krishnaswami SP, Wood Analysisal. et of

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This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons ituximabtherapy forsystemic lupus erythematosus: ortreating arthritis.rheumatoid ScandJImmunol. s and s inflammatoryother rheumatic diseases: rosisinhibitorsfactor andrisk ofseriousinfecti witha tocilizumab: systematic literaturereview a iA, Calabozo M, QuintanaA.Tumor factornecrosis randomized controlled Rheumatol trials. Int. theand safetyefficacy ofthree new biologicsin nn Rheum Dis. 2010;69:1756-61. iewandmetaanalysis efficacy andof safety. BMC Med.2010;25:1-17. JAm Acad Dermatol. 2011;64:1035-50. yofrituximab forthe treatmentactive rheumatoof rmingconsensus a statement. Ann Rheum Dis. 27 ut systematicblockers:TNF a and review meta- 6. matology (Oxford). matology 2011;50:552-62. AJ. ofadverse includingRisk events serious alhaJV,OtukiA MF. systematicreview andmeta- nadults psoriatic with disease: systematic a revie tmentofrheumatoid arthritis.Pharmacotherapy. BaschTebibA, SeriousGossecJ, infectionsL. in controlledtrials. JClinEur Pharmacol.2010;66:4 loMeta-analysisR. the and efficacy of safety of ety of anti-tumourety of necrosis factor intreatments mester GR, mester Emery Dougados et Blockingal. M, P, 2012;13:731-44.B. Sci oledanalyses seriousadverse of Ann events.

addition The oftocilizumab DMARDto therapy for xel AB, AB, JM.xel Gelfandrisk ofThe infection and on in on the the nd w w 9- a a id Page 28of63 Page 29of63 arthritis-a arthritis-a rcts. Arthritismeta-analysis of 35 and Shamliyan T, 83. Lin T, ChoiRhoH, YH, K. Kuntz, T clinical arthritis Journal trials. of Pharmacokinet infections, andserious serious adverse events with 82. Ahadieh S, 82. Checchio FrenchT, Tensfeldt T, G J, trials controlled (RCTs).Annals Rheumatic of the D anddeath lung infections biologics: systemawith A from a systematic a literaturefrom review and meta-analys rheumatoidpatients with arthritis:A systematic re associated different biologicalwith andtargeted s FurstS, 76. Tarp LutaDE, G, Tarp Boers Asmu U, M, and Review Meta-Analysis. Safety.2015;38:869- Drug Certolizumab Profile of in Pegol with Patients Immu 77. De Forest La 77. De Brugneaux M, Utard J, Salliot C G, the Rheumatic of Diseases. 2015;74:176-177. events associated events with using biologicalagents t to TarpS, Andersen79. Tarp U, Lorenzen LS, T, Lindeg network meta-analysis. RheumaticAnnals of the Dise dmards for biologic treatment the rheumatoid art of Hochberg Janssen 78. M, K, K,Broglio Walsem NaAV, Diseases. 2015;74:702. 81. Singh JA,Wells 81. G, Christensen R, Ghogomu E, Ma arthritis:Arheumatoid systematic review and meta- He Y, 80. WongChanE,A, W, Chui Man Lau C, K, et guideline national a panel. andRheumatis Arthritis 75. Capogrosso 75. Sansone A, S, Mantarro M,TuccoriRu in etanercept elderly subjectswith disearheumatic Fleischmann 74. Baumgartner R, SW, Weisman MH, Liu rare analysis harmful of inrandomized effects cont arthritisrheumatoid andthe risk of seriousinfect 73. Bongartz T, 73. Sutton AJ,Sweeting Buchan I, MJ, M 2006;33:2398-408. biologicsforthe treatmentrheumatoid arthritisof Gartlehner 72. Hansen G, RA, BL,Thieda Jonas P,Lo trials. controlled JRheumatol. 2008;35:883-90. intheinhibitors management ofpsoriatic arthritis SaadAA, 71. Symmons DP, Ashcroft Noyce Ris PR, DM. 28

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This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons icsand Pharmacodynamics. 2013;40:S93-S94. Rheumatism. 2012;64:S788-S789. ions ions andmalignancies:systematic review and meta- he safety safety he of anti-TNFbiologicagents inrheumatoid reat diseases:rheumatic Network meta-analysis from ynthetic disease-modifyingynthetic anti-rheumatic drugs in : systematic review: systematic andmetaanalysis randomized of eieral. R, RieseJ, et Meta-analysis of malignanci . Safety. of anti-TNFsinRA patientslife: in real : a : systematic review and metaanalysis.JRheumatol iseases.2013;72:A74. view and view randomised meta-analysis Annalsof trials. m. m. 2013;65:S997-S998. biologic tofacitinibor treatment inrheumatoid rolledJAMA. trials. 2006;295:2275-85. aardStoltenberg HM, M,et al. Serious adverse 28 ticreview andnetwork randomized meta-analysis of ses.Ann RheumDis. 2006;65:379-84. ssenetRiskal. KH, of seriousadverse effects hr comparative The KN. andsafetyefficacy of al.ofSafetytofacitinib in the oftreatment ne-MediatedInflammatory SystematicADiseases: atteson EL, MontoriV.Anti-TNF antibody therapyin es from biologices from registers.Annals the Rheumatic of analysis. Safety.2013;36:852-853. Drug hritisApatients: systematicliterature review and cdonaldMaxwellJ, L, etal. cancer, seriou Risk of ases. 2014; 73:676.ases. dkarniA.Comparison abatacept and of other 888.

ggieroE, Montagnani S, ConvertinoI,Safetyal. et ks andbenefits ks tumor necrosis of factor-alpha T, WhiteB, T, Peloso P. safetyLong term of Results es,

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patients rheumatoidpatients with arthritis. Arthritis Rheum infectionsandall-cause inphase mortality phaII, Cohen S, 97. Radominski SC, Gomez-Reino JJ,L,Wang arthritisrheumatoid clinical ACR/ARHP2012 trials. malignancies,andseriousinfections,serious adver Ahadieh S, 96. Checchio FrenchT, Tensfeldt T, K J, 2007;47(9):1119-28. rheumatoid with arthritis: levelsnot B-cell do cor Breedveld AgarwalF, 95. S, S, M,NF,ShRen Yin Li ClinTher. study. 2003;25(6):1700-21. antibody,monoclonalin rheumatoid with adults arth pharmacokinetic,andsafety assessment adalimuma of 94. Weisman MH, FurstMoreland DE,LW, Weinblatt ME 2015;23(2-3):71-7. JineshS. 93. Pharmaceuticalaspectsof anti-inflam Suppl1):12-8.2005;34(5 Nestorov I.Clinical 92. pharmacokinetics TNF of an Lancet. analysis. 2015;386(9990):258-65. in infection biologicaltreatment ofpatients with Singh JA,Cameron 91. C, NoorbaloochiCullisS, T, Research.2007;68:379-399. AbataceptJL. 90. Kaine for treatmentrheuma the of review.and systematic Clinical MedicineInsights: Volkmann ER,89. Agrawal FurstMaranian H, DE.P, R 2010;62:AB4. randomized Metaanalysis of controlled Journ trials. J,Incidence88. Powers R. Martin seriousinfect of Rheumatology. 2010;37:1343. earlyrheumatoidpatients with arthritis:A meta-an Venson Wiens84. Correr A, R, CJ, R. Pontarolo Effi 29 87. Rieder S, 87. Thompson A, J.Anti-TNF Pope therapy trials. controlled Journal AmericanAcademy of the in antagonists patients with Apsoriaticdisease: s 86. Dommasch A,E, Troxel J,Gelfand ShinD, Abuaba 2011;63:1. inrheumatoid therapy arthritis andankylosing spon Cormier H, 85. Barnetche T,SchaeverbekeT. ris The oftreatmentrheumatoid arthritis. Brazilian Journa

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This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons seIII, extensionand long-term studies of tofaciti ystematicreview and randomized metaanalysis of rheumatoidarthritis:a systematic review and meta- relate with response.clinical JClin Pharmacol. ious with events treatment:methotrexate rishnaswamiRieseS, etal. R, Meta-analysis of awetTM,Rituximabal. pharmacokineticsinpatient TuckerChristensen M, R5, et al.serious Risk of Therapeutics.2010;2:749-760. cacy,andtolerability safety using of abatacept fo matory TNF-blockingmatory drugs. Inflammopharmacology. Annual Meeting. se with tofacitinibevents biologic or intreatment l of PharmaceuticalSciences. 2012;48:781-791. tagonists:howdo theydiffer? Arthritis Semin Rheu atol.2014;66(11):2924-37. 29 alysis of randomized controlled Journal trials. of of of 2011;64:AB8.Dermatology. althe AmericanAcademy of of Dermatology. k of seriousinfection k of with and anti-tnfwithout dylitis:A meta-analysis.Arthritis andRheumatism. and risk of the seriousinfection and in malignancy toid arthritis: A toidarthritis: review. Current Therapeutic ra K. The K. safety ra factornecrosis of tumor ituximabforrheumatoid arthritis: A meta-analysis ritisreceivingconcomitant methotrexate: pilot a Krishnaswami S,Krishnaswami SP, Wood Analysisal. et of

b, a fully human fully a b, anti-tumor necrosis factor-alpha , , EC, Keystone HE, Paulus etEfficacy,al. nibin r the

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Page 30of63 Page 31of63 FurstS, 98. Tarp D.E., Boers Luta G, U, M, Tarp et 30 after primary after jointarthroplasty total insolid org PalmisanoAC, 107. KuhnAW, UrquhartAG, AE.Pour P Rheumatol. 2014;41(2):300-9. belimumabplusstandard therapy 7in patyears over GinzlerEM, 106. JT, WallaceDJ, FurieMerrill RA, Int.2011;31(11):1493-9. arthritis:arheumatoid systematic review and meta- biological different andtargeted synthetic disease 111. Somayaji R,111. C,Barnabe RiskMartin factors L. Committee Advisory Immunization on Practices(ACIP) Harpaz 110. R, Ortega-SanchezSewardI, J.Preventi the literature.review Arch of Surg 2008;143(12):12 MarikVaron 109. J.Requirement PE, ofperioperativ 15.e1. organ transplant recipientstransplant organ afterprimary fare tota Klement 108. MR, PenroseA, Bala SS,WellmanCT, Bo [EpubAug ahead6. print]. of arthritis:arheumatoid systematic review and meta- Lee Bae105. Song YH, SC, The andGG. safeefficacy arthritis.rheumatoid Cochrane DatabaseSystemat of Lopez-Olivo 104. MA, Amezaga Urruela M, McGahan L, intreatmentrheumatoid arthritis clinical trials. seriousinfections analysis of tofacitinib with and AhadiehStrandV, 103. FrenchS, GeierJ,J, Krishn systemicpatients with lupus erythematosus. Arthrit placebo-controlledstudy ofabelimumab, monoclonal R,Furie Zamani102. Petri M, Cervera O, R, Wallace ClinRheumatol. 2010;29(7):707-16. MurrayE, 101. Perry M. Off-labelrituximab use of systematicA erythematosus: review ofoff-label use Ramos-Casals Soto100. M, Cuadrado MJ, MJ, Khamasht synovial suppresses JAK1-STAT signalling inrheumat Boyle 99. Soma HodgeDL, KavanaughJ,K, A, Mandel Junepp2015, 176-177. rheumatoid arthritis.rheumatoid Open J Rheumatol 2013;7:119-2

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This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons Arthritis Res Ther. 2015;17:362. an transplant a recipients: caseseries.Int Orthop biologicdisease-modifying antirheumatic drug al. Risk ofseriousadverse effects associated wit Stohl W, ChathamStohl W, WW. Disease andsafety control of aswami S, aswami S,Systematical. Menon et review and met -modifyinganti-rheumaticdrugs inpatients with forinfection totalfollowing in joint arthroplasty l knee arthroplasty?l knee JArthroplasty. 2016;31(3):609 in systemiclupus erythematosus: systematic a revie 30 22-6. DJ, Aal. Tegzová D, III,et phase randomized, ty of rituximab tyof forthe oftreatment active on of herpes on zoster: of recommendation ofthe is Rheum. 2011;63(12):3918-30. in cases. Lupus. 188 2009;18(9):767-76. analysisrandomised of trials. Abstracts Scientific analysisrandomized of controlled trials. Rheumatol e e dosesstress ofcorticosteroids: systematic a oidAnnarthritis. Rheum Dis. 2015;74(6):1311-6. ientswith lupussystemic erythematosus.J icIssueReviews2015, Art. 1. No.:CD007356. D, D, TheMease inhibitorJAK P. tofacitinib

4. lognesi SeylerHow MP, previous TM. do solid . MMWR MMWR . Recomm Rep. 2008;57(RR-5):1-30. antibody that inhibitsantibody that lymphocyte B stimulator, in ost-operative andmedicalsurgical complications Pollono EN, Suarez-AlmazorEN, Pollono ME. Rituximabfor a MA. Rituximab MA. a lupusinsystemic . 2016 h

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severe posteriorsevere keratitis, severeuveitis/retinal cholecystitis, lupuscholecystitis, hepatitis, proteinlosing ente (with weakness,muscle highnot just enzymes), lupu includingcutaneousvasculitis), hemorrha pulmonary CNSnephritis,lupus, severehemolytic anemia(Hgb< †All patients†All carryingdiagnoses listed,the withou severe Not SLE: opticneuropathy ischemic (derivedfrom SELENA- the Severe Severe SLE: foroptimizedsurgery: includes *SLE patients not with severe or severeSL drugrheumatic therapy time at the of surgery.† surgical appropriate candidates, undergoing electiv age Adultsdiagnosed≥ 18 SpA, including RA, with A Populations Table

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Accepted ArticleNot currentlyfortreatedabove manifestations.

This article isprotected by copyright. All rights reserved. thisguideline. Arthritis &Rheumatology John Wiley& Sons

vasculitis,severescleritis, opticneuritis, anter ropathy, inflammation/myosit malabsorption, orbital t restriction t those to classificationmeeting crite E,defined follows as e THATKA, and e are or treated who with anti- S and PsA , JIA, , SLE*, andSPsA or who deemed are be to s s (vasculitis),enteritis lupus pancreatitis, 9.9), PLT<50,000, vasculitis (other than mild ge, lupusmyocarditis, severepneumonitis, myositis SLEDAI Flare Index SLEDAI andBILAG (22-24).2004) evere evere organ manifestations:lupus , , andwhobeen have medically ior ria. is,

Page 32of63 Page 33of63 Doxycycline Leflunomid Hydroxychloroquine S M surgery.through DMARD 2. Table Tacrolimus C Azathioprine Mycophenolate perioperativeperiod. CONTINUEmedicationsthese the in SEVERE prior surgery.todays TofacitinibSTOP(Xeljanz): medication this 7 (Benlysta) Belimumab (Stelara)Ustekinumab (Cosentyx) Secukinumab Anakinra(Kineret) Tocilizumab(Actemra) Rituximab(Rituxan) Certol (Orencia) Abatacept (Remicade) Infliximab Golimumab (Simponi) (Enbrel)Etanercept Adalimumab (Humira) site surgical infectionsystemicor infection. absenceofwound healing problems, days afterminimum the14 surgery in thedosing cycle. RESUME atmedications and schedulesurgery surgeryat theend of BIOLOGICS: ulfasalazine yclosporine ethotrexate izumab(Cimzia)

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This article isprotected by copyright. All rights reserved. medications : Arthritis &Rheumatology John Wiley& Sons W weeks Weekly Dosing I Daily Daily twice Once dailyor twice Once dailyor Weekly Dosing I (IV daily Twice andPO) daily Twice D daily Twice Dosing Interval D weeks Every 4 E E Daily weeks (IV)every 4 (SQ) Every week or every months4-6 doses apart2 2 weeks 4 Every weeks2 o weekly (SQ) (IV) Monthly or Ev weeks (IV)every 8 weeks Every 4

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Arthritis &Rheumatology John Wiley& Sons Twice daily (IV daily Twice andPO) daily Twice D daily Twice Dosing Interval aily aily dailyor twice iononlineprovided bypharmaceutical companies. lasty Medication in Medication Patients withRheumatic Diseases ociation of Hip ociation and of GuidelineKnee Surgeons

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Page 34of63 Page 35of63 elective THA or TKA, and plan the surgery at the the en at surgery the plan TKA, and electiveor THA hydroxychloroquine, and/or sulfasalazine (non-biolo and/or sulfasalazine hydroxychloroquine, RA, SpA including AS and PsA, JIA, or SLE: Withhold SLE: PsA,JIA, or and AS including RA,SpA SLE††: JIA**, or PsA#, and AS¶ including SpA§RA‡, RECOMMENDATION/STRENGTHOF RECOMMENDATION(CONDITIO elective THA*or TKA†. Table3. Recommendations for perioperative manageme or TKA. or tofa JIA: Withhold PsA,or and AS including RA,SpA • • • • • • • • • • • • •

increased, but in fact decreased, when DMARDs were DMARDswhen factdecreased, in but increased, DMARDs th at discontinuing vs. RCTs§§ofcontinuing RCTs (non-surgical) demonstrated an increase inf an in demonstrated RCTs(non-surgical) Evidence indicates a low infection risk with these riskthese with lowinfection a Evidenceindicates (42,43), yet flares were significantly less importa significantly were flares(42,43), yet and frequently, occur surgery after flares Disease Avoiding infection was significantly more important significantly was Avoidinginfection A systematic review of rituximab vs. placebo (and o (and vs. rituximab placebo of systematicreview A therapy and may not be associated with low-dosebio with notassociated be may and therapy Meta-analysis and network meta-analysis revealed th revealed meta-analysis network and Meta-analysis Serum half-life may not correspond to the duration duration the to correspond not may Serumhalf-life as more relevant in determining the withholding int withholding the determining in asmore relevant withheld dose during week 9. 9. week dose during withheld to support separating biologics management in the p the in management biologics separating support to Until further studies have clarified and establishe and clarified have studies further Until For SLE, there was paucity of data supporting perio supporting data of therewas SLE, paucity For 0.62-1.17) (98,105) to RR= 0.89 (95% CI 0.7-1.14). CI0.7-1.14). (95% RR= to 0.89 0.62-1.17)(98,105) non-surgical patients with RA and SLE revealed SLE the and RAwith patients non-surgical Observational studies reveal that patients with SLEwith patients revealthat studies Observational adverse events after surgery. surgery. after adverseevents Belimumab is indicated for use in non-severe SLE, w SLE, non-severe in foruse is Belimumab indicated possible in the week after the first withheld dose withheld first after week the possible the in treated patients guideline, thisusing example, For weeks, would schedule their surgery during week 5. week 5. during surgery their schedule weeks,would Patients treated with adalimumab, dosed at 2 week i week 2 at dosed adalimumab, with treated Patients

Accepted every dosedwhen infliximab, with treated patients Article

This article is protected by copyright. All rights reserved. d of the dosing cycle for that specific medication. specific theof that d cyclefor dosing all current biologics (see Table 2) prior to surge to prior biologics2) Table (see current all citinib for at least 7 days prior to surgery to pat in leastdaysprior 7 at for citinib Continue the current dose of methotrexate,leflunom of dose current the Continue gic DMARDs‡‡) for patients undergoing elective THA elective undergoing patients for gic DMARDs‡‡) nt than infection for the patient panel. panel. patient forthe infection than nt d differences in risk between biologics, there was therewas biologics, riskbetween in differences d during month 7. Patients receiving belimumab, which receivingPatients7. belimumab, month during DMARDs in settings other than THA and TKA (41). TKA (41). THA and settings than other DMARDsin continuing DMARDs decreases the risk [RR 0.06 (95% (95% [RR 0.06 risk the DMARDsdecreases continuing with rituximab every 6 months would schedule their schedule would months 6 every rituximab with , particularly those with active or severe SLE, are SLE, severe or active thosewith particularly , perative benefit in SLE (100-102). (100-102). SLE benefit in perative risk of all serious adverse events with a range frorange a eventswith adverseserious ofall risk ccasionally vs. control treatment including non-bio including vs.treatment control ccasionally ection risk associated with use of all biologics (4 use biologics of all with riskectionassociated 8 weeks, would schedule their surgery in the week the in a surgery schedule their would weeks, 8 to patients than flares for patients with RA and J RAand with flares forpatients than patients to erval (92-95). erval (92-95). of the immune-suppressant effect, so the dosing cyc dosing the so immune-suppressant ofthe effect, hich is not thought to increase risk perioperative thought not is hich ntervals, would plan their surgery during week thre week surgeryduring their plan would ntervals, e time of surgery revealed that the riskof infecti the that ofsurgeryrevealed etime erioperative period (44-90). (44-90). period erioperative at infection risk for biologics is strongly associa strongly is riskinfection for biologics at logics (91). (91). logics continued, with an RR¶¶ of 0.39 (95% CI 0.17-0.91) ofCI0.390.17-0.91) (95% RR¶¶ an with continued, ntof anti Arthritis &Rheumatology John Wiley &Sons - rheumaticdrug therapy patientsin withrheumatic d NAL)

ients with undergoing THA undergoing with ients ry in patients undergoing undergoing patients in ry

ide, insufficient evidence evidence insufficient or TKA. TKA. or at a higher riskfor higher a at 4-90). 4-90). m 0.85 (95% CI (95% m0.85 ted with high-dose high-dose with ted IA. (102,106). (102,106). ons was not not was ons logic DMARD) in in logic DMARD) surgery when surgery is given every 4 every is given CI 0.0-1.10)] CI0.0-1.10)] fter the first first the fter le was chosen chosen le was e, while while e, (39,40). (39,40). Level ofLevel Evidence Low Moderate Lowto Low iseasesundergoing

rather than shorter or longer periods of withholdin of orlonger periods shorter than rather out, there is no significant swelling, erythema or or significant erythema is no swelling, there out, surgery in all patients undergoing THA or TKA. or THA undergoing all in patients surgery T THA or undergoing 2) Table (see with all patients glucocorticoids for their rheumatic condition and and u rheumatic condition their for glucocorticoids show wound the TKA once and to THA undergoing prior RA, SpA including AS and PsA, or SLE, Continue the the SLE, PsA,or Continue and AS including RA,SpA b SLE: Restart or PsA,JIA and AS including RA,SpA myco dose of current the Withhold severe): SLE(not mycophenol of dose current the SLE: Severe Continue physiologic glucocorticoid doses (so-called “stress (so-called doses glucocorticoid physiologic • • • • • • • • • • • •

days. days. non-s ofsurgical and forabsence clinicaljudgment an RR of 5.7 (95% CI 1.8-18.1) (97). (97). CIRR1.8-18.1) of5.7 (95% an may change in the future, as physician and patient patient and physician as future, the in change may re panel the Therefore, is withheld. drug after the hal serum short extremely an has drug this Although The decision to restart anti-rheumatic therapy shou therapy restart anti-rheumatic to Thedecision This recommendation specifically refers to adults w adults refers to specifically Thisrecommendation The time course to flares in not-severe SLE is not is not SLE not-severe in flares to course The time treatment including non-biologic DMARDs) in non-sur in DMARDs) non-biologic treatmentincluding meta- and reviews systematic evidencefrom Indirect increased with tofacitinib with odds/hazards/risk r odds/hazards/risk with tofacitinib with increased The morbidity of prosthetic joint infection may be may infection joint ofprosthetic Themorbidity elsewhere. absence the surgery in after days 3-5 restartedat week to one prior withheld be can Thesemedications time courses for onset and reversal (109,110). reversal (109,110). and foronset timecourses interference with t-cell co-stimulatory signaling, co-stimulatory t-cell with interference There are multiple mechanisms postulated forimmune postulated mechanisms multiple There are medications. to prior days of7 withhold conservative a Suggest The panel recognized that there is much uncertainty thereis much that recognized The panel perioperative medication management in patients wit patients in management medication perioperative Indirect evidence with organ transplant patients su patients transplant organ with evidence Indirect Decisions regarding elective surgery in patients wi patients in surgery elective Decisionsregarding

Accepted Article rheumatologist.

This article is protected by copyright. All rights reserved. drainage, and there is no clinical evidence of non- of clinical is evidence no there and drainage, dosing”). dosing”). iologic therapy in patients with for whom biologic whom for with patients in therapy iologic KA. ndergoing THA or TKA, rather than administering per than TKA,ndergoingTHA rather or g. current daily dose of glucocorticoids in patients w patients in glucocorticoids of daily current dose phenolate mofetil, azathioprine, cyclosporine, or t or cyclosporine, azathioprine, mofetil, phenolate ate, mofetil, azathioprine, cyclosporine, or tacrol or cyclosporine, mofetil,ate, azathioprine, s evidence of healing (normally about 14days), all about healingof (normally evidence s and blocking the de novo pathway ofpurine synthesi pathway novo de the blocking and known. known. cognized that the recommendation for the duration o duration forthe recommendation the that cognized of wound healing complications or infection at the the at infection or complications healing wound of th severe SLE should be made on an individual basis an madeon be should SLE severe th atios 2.91 (95% CI 2.27-3.74) (96) and higher risk higher and (96) CI2.27-3.74) (95% 2.91 atios more severe than a flare in SLE that is not severe. is not that flareSLE a in than severe more surgery until additional researchunderst increases additional surgeryuntil urgical site infections. Normal wound closure typic closure wound Normal infections. site urgical pports continuing anti-rejection therapy through su through therapy anti-rejection continuing pports experience with this drug grows (44,50,51,54,80,82, experience grows drug thiswith ith RA, AS, PsA or SLE, who are receiving glucocort receiving are who PsASLE, or AS, RA, ith ld be based on careful assessment of the patient’s patient’s ofthe careful assessment on based be ld and little published experience regarding risks as little regarding experience and published f-life, little is known about the duration ofimmun duration the about little is known f-life, analyses of tofacitinib vs. placebo (and occasional (and vs.placebo oftofacitinib analyses surgery, permitting return of some immune function immune ofsome return permitting surgery, gical patients shows that the risk of serious infecserious riskof the that shows gicalpatients h severe SLE. SLE. severe h suppression with these medications, including leuk including medications, thesewith suppression Arthritis &Rheumatology John Wiley &Sons surgical site infections, surgicalsiteinfections, therapy was withheld withheld was therapy ho are receiving are ho acrolimus prior to to prior acrolimus in through surgery imus ioperative supra- ioperative sutures/staples are are sutures/staples of all infections with with infections of all

surgicalsite or anding of these ofthese anding ally requires 14 requires ally s, with different different s,with icoids for their icoidsfortheir sociated with sociated with the patient’s patient’s the with osuppression osuppression tions was was tions wound status and statusand wound rgery (107,108). rgery ly vs. ly control 96,99). 96,99). f withholding fwithholding openia, openia, , and and , Low Low Low Low Low Page 36of63 Page 37of63 ¶¶ Relative risk Relative ¶¶ risk trials controlled §§Randomized drugs anti-rheumatic ‡‡Disease-modifying erythematosus lupus ††Systemic arthritis idiopathic **Juvenile #Psoriaticarthritis spondylitis Ankylosing ¶ §Spondyloarthritis arthritis ‡Rheumatoid ## † arthroplasty *hip Total Total knee arthroplasty kneearthroplasty Total Centers for Disease Control Control forDisease Centers • • •

glucocorticoids during development, or to thosepat to or development, during glucocorticoids rheumatic condition, and does not refer patients does not to and condition, rheumatic observational studies demonstrate an increase ar an in studiesdemonstrate observational Optimization for THA and TKA should include careful include should TKA forTHA and Optimization to surgery (110,111). surgery(110,111). to primary hypothalamic disease. disease. hypothalamic primary mean prednisone (or equivalent) dose was ≤ 16 mgda ≤dose 16 was equivalent) (or mean prednisone hemodyna on information found review Theliterature

Accepted Articleforimmunosuppressi cut-off the considers The CDC##

This article is protected by copyright. All rights reserved. receiving glucocorticoids for JIA who may have recmay JIAwho forglucocorticoids receiving throplasty infection risk for chronic steroidusers riskinfectionfor chronic throplasty ients receiving glucocorticoids with primary adrena primary with glucocorticoids ientsreceiving ly tapering the GC dose to below 20 mg/daily when p whenmg/daily below 20 to GC the dose tapering ly on at 20 mg of prednisone/day for at least weeks, 2at for 20mg ofprednisone/day at on ily. ily. mic instability in a SLR for patients with rheumati with SLR forpatients a in micinstability Arthritis &Rheumatology John Wiley &Sons at 15 mg/day. 15mg/day. at eived l insufficiency or or insufficiency l c diseases whose whose diseases c and and ossible prior prior ossible (http://www.rheumatology.org/Practice-Quality/Clini guideline This followed the AmericanCollege of Rhe MethodologyOverview SUPPLEMENTARYAPPENDIX Methods 1: limitations respectlimitations with to ofimprecisibias, risk begin Randomizedtrials as highevidence, quality b GRADE Usingthe approach,quality the evidence i of quality availablethe of the andfacilito evidence Recommendations Gradingof Assessment, Development Observational Observational are ratedstudies typically as low or of relative benefits of andharms the treatment of opt GRADE methodologyspecifies that recommendations ar is size ineffect sufficiently large large studies. (i.e., confidencein (i.e., the estimatedan effects of in would thewould recommendation,make andall almost al or the strength recommendations. of A strongrecommen conditional strong or and(3) distinction clear a i recommendationUsing a GRADE, becan eitherin favo higher much avoiding value on anda infection lower in Panel, keeping the with patientof a advisviews requirerecommendations theestimating relative val recommendation the to is thetrade-offbetween desi

Accepted Article

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John Wiley& Sons (4,5) on, inconsistency, on, indirectness, orbiapublication s s madebetweenquality the the evidence of andthe tervention), andtervention),patients’ valuesandpreferences. tate thetate development recommendations ofthe (1). qualitylow very evidence, but rated be up may if ory ory estimatedpanel,that typical place apatients ut rated be down may as result a of serious ionsunderconsideration, the ofthe quality eviden umatology(ACR) guideline development process s rated as high, s as rated low,moderate, very low. or avoidingdisease value a on flare. uepatients place inthe Voting outcomes. The rableandundesirable outcomes; cal-Support/Clinical-Practice-Guidelines),using th l informed patientsinformed l the would choose r or against or ther interventionproposed and either dation indicates dation that allalmost physicians all or e made based e on made consideration a balance of the andEvaluation (GRADE) methodologyrateto s s (2). Key Key the the ce ce e e Page 38of63 Page 39of63 conditional guidelineare due theto quality of the recommended coursebutaaction, of minority might Conditional recommendationsarein those which most action, recommended and additional that researchwo AmericanAssociation ofHip Surgeons andKnee (AAHK aproject This was collaboration between the Americ InvolvedTeams identified. was the much evidence of used from came non-surgical st addressingdirectlyidentified about questions when findings; the resultsfindings; the the of patient u were meeting panel patient A was convened patientdiscussto val librarian. ACR support The staff. literatureof search was per Literature The Review comprisedTeam was of 8 ortho disease experts, patient representative,1 andS an 2 orthopaedists, of rheumatologists, 3 1 methodolog participation with the Literature of ReviewTeam an Patient/Intervention/Comparator/Outcomesque(PICO) helped expertise define scopethe projectthe of an and a and AY), methodologistwhohad GRADE expertis BS)investigators (SG, who project, co-led the the both the from organizations.LeadershipCore A Team

Accepted Article

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons ACR ACR and AAHKSLiterature ReviewTeam leaders (JS evidence, as therewas littlehigh evidenc quality sed part as of the andweighingbenefits of risks b formed the assistancewith researchmedicalof a LE expert, the supportwith ofthe staff. ACR d the drafted uesandpreferences relative outcomesto andPICO dthe Voting ExpertPanel. The Panelwas comprised to stopto re-start or rheumatic medications, and anofCollegeRheumatology andthe (ACR) ist,1 rheumatology methodologist,2 infectious udies. In addition, needudies.In addition, for researchadditional comprised was ACR andof AAHKSco-principal not (6,7). Allthe not recommendations of inthis paedists and6 rheumatologists, whohadthe uldunlikely be to change recommendation. the S); all participatingall S); teams includedrepresentation informed patientsinformed the would choose e (GG). Expertse content with andmethodology stions (see liststions(see ofPICO questions inAppendix 3), e ythe

11 adults with11 and JIA, RA hadundergon of allwhom A patient panel patient A was convenedday priorthe theto V PanelPatient by thepresented Literature ReviewTeam leaders. andreframed review the PICOquestions into recomme methodology,andwas supported by ACR staff. Vo The duringdiscussions their the day.following Voting presented the to two Panelby core team memb valuesand preferences The patient of andpanelthe relevantpersonal experiences theto questions and as Review Team each PICO discussed. question was Th afterTHA frequent patientand TKA.panel The revi to importancecompared the flares ofdisease of lin rareinfection, post-operative linked events coto patients specificallyqueriedwere relevanton the andbackgroundscope of theguideline project deter completedresearchand guideline methodology webina ACR andstaffone person facilitated day-long the d duration diseasemean of was (range years 26 t of 8 includedwere inthe panel. The the mean age par of patient, per with onlyone reporting apatient pros an SLE expert,patient SLE an2 representatives,2 rheumat Panel, Voting waswhich comprised of 6 orthopaedist

Accepted Article

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons ntinuedimmunosuppressant DMARDandbiologic use, importanceofsurgical-site non-surgical or site theticjointinfection. No SLEpatients with SPA or iscussion.The participants, all had of whom ked to kedthewithholdingto medications, arewhich ewedthe evidence synthesized the by Literature ology methodologists,as ology inexpertanwell as GRADE o 42). Twoo 42). members of the LeadershipCore Team judgeimportance the of accordingly.the outcomes oting Panel otingPanel meeting July consistingon 2016, 10, of theresultsvoting for recommendation each were ticipants was (rangeyears 47 23 andthe 71) of to mined at face-to-facethemined first The meeting. e THATKA, range e a or with 1 to jointsreplace of 8 s, 5 rheumatologists,s, 5 infectiousandisease expert, e participants e encouragedwere considertotheir tingdiscussed Panel the results the literature of ers whofacilitated ers patient panelthe meeting ndations afterreviewing ndations the evidence synthesis rs prior prior rs meeting, to were presented the

d

Page 40of63 Page 41of63 PICO Question DevelopmentPICO this with manuscript.authorIn addition, disclosur disclosures,participantUpdated as as ACR well com face-to-face Voting Panel verbaldisclosur meeting, Participantdisclosures includedwere inthe projec intellectual conflicts countedwere not conflict as and important requiredwere disclosed, be to butbe and biologics of DMARDs in rheumaticpatients with addition, disclosures addition, of all were participants shar Intellectual suchconflicts, prior a publication as participate. to ACR policy, Per everyonewhowas consideredfor int DisclosuresandManagement of Conflicts of Interest disclosures).Theupon agreed nextstep wascomp to guideline authorship), for disclosed relationshall focus of this focus guidelineof was stoptemporarilyto or positivelyornegatively byaffected care delivered companies” “affected (i.e., companies or organizati relationships relationships consideredwere conflictsinterest of time/effort) wastime/effort) withcompany a that manufactured o so,Evenin involved. policies,keeping ACR with in were no affected no were companies guideline,for and this situations wheresurgery had been scheduledalready

Accepted Article

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons or scientificpresentation perioperative on manage ips XXlink(see forfull details on participant ed, in ed, with writing, each project participant. At t ed based on intellectualon based their ed conflictalone. dividualsprimary whose employment(> 51% of work restartmedications that were prescribed, i already in withaccordance the guideline)determineto whi esare alsoincluded inthis paper. for this purposes However,project.of because the t plan t was postedthat forpublic online comment. esprovidedbeforewere any discussion. content ons that consideredreasonablywere likely be to therefore,no conflictinterest individuof for any mitteereviewerdisclosures, are included online causetheywere ubiquitous, participants with diseases undergoing diseases THA/TKA, recognizedwere as ellectualinvolvement inthe (i.e., project conside aredisclosuresagainst previously a drafted list o

,was decidedit the by ACR thereand AAHKS that r soldr therapeutics diagnostics or notwere eligibl he he ment als als n

red red ch f In e e Core The Leadership Team drafted proj initially the Team fortheir Team areview at face-to-face meeting whe questions, which thenwere presentedtheto Expert sufficient power sufficient studyfor a with rare a endpoint). inthe andpopulationsTKA interest, primariof due taking the not medicationsinterest, of orcomparin data highRCT available quality comparingthe risk on event the orderof2.4%0.5to (8,9). group The outcome withThe the greatest for weight guide this remote surgicalsite infection,death,or andlong- were critical,flare the most literaturealthough o superficial surgery, or surgical siteand non-surgi determined eventually that infection(both deep sur andrevised comment accordingly. initiallgroup The andemail electronic newsletters, andwas alsopost includingelementsand project these details, other the drugs ofthe interest: eventsadverse inpatients inflammatory with arthri studies perioperative outside of the setting, andt recommendations the inform the first – indir sought 1.

associated associated use with of each candidate of the drugs evidence: Indirect is What fortheserious risk adv Accepted Article

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons cal site cal infections days90 within surgery) and of n outcomesother assuch hospital readmission, non- term arthroplasty sought.outcome was also hesecondsought establishto the baseline risk of To gap, this address questions two includedwere t of infection of afterTHA in or TKA taking those versu acknowledged that not there woulddirectlikely be lypracticalto reasons (theprovideto inability ect principles key scope, andrelevant clinical (PI wassent andAAHKS ACR to membersvia broadcast g thebackground adverse risk eventsof afterTHA tisundergoing THATKA not whoreceivingwere or edtheand AAHKS ACR on websites forpublic y y wideconsidered a range ofoutcomes, but linewas deep infection, surgical-site uncommonan gicalsite,reported thewithin yearafter first re the projectre the plan was defined. project The plan, ectdrug-related evidence of effectsadverse from Panel, the Voting Panel,the Panel,and Literature the Review erse infections, erse events, orhospitalizations, outsidesurgical ofthe setting, limiting disease CO) s o o

Page 42of63 Page 43of63 Systematic Systematic Synthesisofthe Literature

1. 2. Study 2. Selection title andabstract title andfull screening, manuscript 1 separately with separately “arthroplasty;”no randomized trial search termsinclusive the disease statesof S (RA, finalAsearch 2). performed for was time the perio PICO 2, for31PICO 3,for 20 PICO4, and for69ba Literature search Literature strategies onbased PICOquestion keyword/title/abstractwords Cochrane inthe Librar (SupplementaryEmbase Appendix Text 1). words were database:MedicalSubject Headings(MeSH)for PubMe search strategiesThe were using thedeveloped cont (mid-1960s+)from January 1, through1980, March 6, Strategies(PRESS).Searches performedwere in Emba reviewedwere strategies by another librarimedical review leaders,systematic researchandlibrarian a

Literature Literature Searches 2.

RA, SpA,JIA, RA, or SLE independent use of the anti of is background What the risk foradverse asso events the search systematictothe literaturereviews (SLRs)

Accepted Article JIA,andincluding observationalstudies inSLE, as

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Arthritis &Rheumatology John Wiley& Sons 9papers includedwere relevant as for fo PICO 1, 9 pAincluding JIA,and ASandcoupled PsA, SLE) ckgroundquestions 5 and6 Appendix (Supplementary , , theinput from GRADEwith consultant.The search dofJanuary 1 September to 8,using2016, the s s identifiedwere that relevantwere guideli the to anusing the Review ElectronicPeer Search of s s developedwere by principal the investigators,th y. resultedy. in Searches 2,230 references. total Aft rolledvocabulary or thesauri language for each 2016. se (1974+), the se Cochrane LibraryandPubMed dandCochrane Library; and for Emtree terms used inused PubMedandEmbase, and indicated? and meta-analyses(MAS) forRA, SpA,and -rheumatic interest? medications of ciated with THATKA ciated inpatients or with r ne. er e panel participants recognizedparticipantspanel post-operative that f patient panelThe weighed evidence the first andan Movingfrom Evidenceto Recommendations panel Julypatient andon 2016,the 10, Voting Pane reviewed the summary evidence anddiscussed possibl design,inconsistency, indirectness, imprecision, a important (i.e., outcome high, low, moderate, or ve andparticipants,number needed to treat.Werated andharms forbenefits interest outcomes of across abstracting datafor from observationalstudies. Wh questions for most PICO as plannedusing GRADEprofi toduequestion; lack the ofRCTs, unablewewere t questions. An PICO evidence summary prepared was as Literature The Review analyzed Team andsynthesized EvidenceReport3. Formulation manuscripts thenwere reviewed in their entirety. the fullwith the text papers of available byi two LS, JG,PS, VD),MM, with a thirdreviewer(AY orJ performed abstract was by independent reviewers two grouped results by their pertinentwithmatch the P softwareDistillerSR(available at:http://systemat and infection andHowever,infection was rare. importance the th far greaterthethanfar importance attachedflares. to

Accepted Article

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons ndependentfromreviewers the same Selectedpool. ic-review.net/)was used literature screentothe s S) resolving S) Theconflicts. second done screen was nd considerations.other Core The Leadership Team They unablepreciselywereto thequantify differe lareswere common andvery difficultfor them, very o prepare GRADEo prepare Summary of Findingstables (SoF) l thel day.following ry intotaking account low), limitations study of ICOquestions. Duplicatescreening each titlean of studies, the relativestudies, the (95%effect CI), the number o en available, the available, the en summaries evidence containedthe alyzed it in it context alyzed the of theirexperiences. The eyattachedinfection to at thesurgery time of was the quality forof each evidence critical and ler(GRADEpro) software. Microsoft wasExcel used data from included from data studies that addressed the e evidence e gapsprior theto presentation theto from among from pool a AY, (BJ, SS,MT, MG,SL,LM, a PowerPoint a presentation each for PICO earch

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Page 44of63 Page 45of63 joint, amputation, death).joint, flarespercei wereWhile The patients The endurance viewed during perioperat the noting thatinvalue, it was greater 10:1than or 2 on the positiveeventualon outcomesofbetter mobilit includingsurgery patient’sendat a timing the of haddeveloppotentialto into significantly p worse possible. theas From perspective the patients, of Patients agreed Patients that close between coordination the theachievement positive of outcomes theysought. introduce and/or healthother issues, patient which meeting. The panel The meeting. voted anonymously andan con 80% asinput fromthe well the panel, patient which was chaired by by co-PIs,chaired discussedthe thein evidence th reformulated asbeen drafted recommendation stateme nextday, The the Voting decideto Panelmet fi the managementofpatients as with thereSLE, l no were they noted that uncomfortableprovidingwere import an as prevented unexpected related benefit u the to foruse support ofsupra-physiologic s “stress-dose thetoInregards recommendation forglucocorticoid considered. which about risks theywere willingtaketo theyif presence a The coordinatedof approach was importan

Accepted Article

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons 0:1. 0:1. feltThey that flares represented a ris “known drug to cycle dosing infectionminimize confidentwere that their individual were needs there was no infection “average” as – infectionall ossibleoutcomes flaresthan (e.g., losspermanent e e clinicalcontext of their experience and expertis teroids,”but theywondered whetherflares were ved as difficult,infectionved as could recovery postpone nal guidelinerecommendations. PICOquestions had summarized andpresented during Voting the Panel s felt wass unacceptable because delayit would y y andpain,while less minimizingrisks as major mu se steroids.”of “stress-dose Finally, the patients andrheumatologistthe orthopaedist was essential, patientsdosing, agreed that therewas little upusin group.patients the ive periodive as ina “job” whichtask is their focto ant inputrecommendations ant into the for t to them andthem to influencet would their perspectives sensus wasas usedsensus forthe a threshold nts,forthe panel’s consideration. panel, The and flare risks. flare k.” e, as e, s s

of of us ch

subcommitteesthe ACR of ACR and AAHKS: Guidelines journaltoIn addition peer reviews, the manuscript infection, a rareinfection, a event, highersignificantly than clear guidanceprovided very their valueson andpr rating the to down evidence reported wherestudies Final Review Final theManuscript and Approvalof timing suggested surgery inrelation of drug the to werecommended When a be that medication withheld, unanimously.Insome instances, the combinedpanel Allrecommendations wereby supported ofover 80% t risks. about inputtheinformhelped Voting Panel’sfinaldecisi THA inwith or patientTKA populationsthe addresse undergoing surgery. Therefore, observationalstudie drug-related studies of infectionrisk are derived was duration particularly relevant instudies addre infectionriskswhich from THAmarkedly vary or TKA heterogeneouswere studies regard with surgicalto ofthe forMuch evidence thisindirec guideline was attended who the summarize meeting to evidence the review leaders,systematic GRADE the andexpert,se discussionsadditional before re-voting. Voting The if recommendation; 80% consensus notachieved was d

Accepted Article

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by by andAAHKSthe ACR post-operativeflares, which were (10,11); frequent fromand are notRCTs performed inpatients ons even in absence ons highthe even of literature quality -dosinginterval. ssingglucocorticoid“stress-dose” therapy. Most discussionsPanelmeeting supportedwere by the wasreviewed by following the and committees t, t, loweredwhich evidence ratings. quality Included eferences,ratingthe importance ofperioperative procedures,including foot orproceduresinspine s s determinetoused were baseline risk associated d guideline, this by andadditionally, imprecision .inbaselineHeterogeneity dose medication and lected membersofthe systematicreview team, on small numbers. onsmall patient The however, panelists, PICO questions PICO into onefinal recommendation. he panel, andpanel,all he but supportedone were anddetails,provide as requested. Subcommittee; ACRSubcommittee; Quality Care Committee; of uringinitialanvote,the membersheldpanel we included we recommendation a forthe

this this led

Page 46of63 Page 47of63 themade within guideline, served pebutrather, as ACR andAAHKS These oversightdidgroups not make o Board ACR ofDirectors; AAHKS BasedEvidence Medici

Accepted Article

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons er reviewers. er ne Committee; ne andAAHKS Board of Directors. r specific recommendationsmandatethat be REFERENCES 11. 10. 9. 7. 8. 6. 5. 2. 1. 4. 3.

optimal amount optimal ofinformation to preferences elicit multinationalstructured interview-based study comb thepreferences expected of hipefficacy arthros of TikkinenZhang KA, Y, Agoritsas T, Ayeni OR, Alexand 2):22-23. Recommendations Advisory of the Committee Immuni on Centers for Disease ControlandGeneralPrevention. direction direction andJClinstrength. Epidemiol 2013;66(7) 15.Goingguidelines: from recommendatito evidence SchunemannJC, Andrews HJ,AD,OxmanK, Pottie Meer patient perspectives. Healthpatient 2015;18(6):2318Expect forpreferences antithrombotic oral therapy inpati Alonso-Coello P, MontoriVM, MG, Diaz PJ, Devereaux infection in infection the States. United JArthroplasty 2012 E,SM, Kurtz Lau Watson H, Schmier JK, ParviziJ.E recommendations.JClinEpidemiol 2013;66(7):719-25 from Going evidence recommendations:to the signifi GuyattJ, Andrews Oxman G, Alderson AD, P,P, Dahm approach. JClinapproach.Epidemiol 2016;72:45-55. interpretto professionals and recommendations use SantessoI, Neumann AklN, Rind EA, Vandvik DM, PO, evidence”anditwhy is important clinicians?.to B AD,Oxman GH,Guyatt Vist Falck-Ytter Kunz R, GE, Y 2008;336(7650):924-6. rating consensus on quality andof strengt evidence AD,Oxman GH,Guyatt Vist KunzR, GE, Falck-Ytter Y informed healthcareinformed choices. Clinicalpractice2: g toEvidence (EtD) Decision systematicframeworks: a Alonso-Coello P, AD,Oxman Brignardello-PJ,Moberg

Accepted Articlerecommendations.BMJ 2008;336(7652):1049-51. AD,Oxman GH,Guyatt Falck-YtterVist Kunz R, Y, GE

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons uidelines.BMJ 2016;353:i2089. MJ MJ 2008;336(7651):995-8. conomic burdenconomic periprosthetic jointof ;27(8Suppl):61-5.e1. :726-35. copyforosteoarthritis: a forprotocol a ents with atrialents with fibrillation: physician and h ofrecommendations.BMJ . BMJ. Open 2014;4(10):e005536. , Schunemann , HJ,et al. What“quality is of ,Alonso-Coello al. anP, et GRADE: emerging , LiberatiA,al. , fromet Going to evidence Recommendations Immunization: on er P, Imam er P, al. M, and et Patients’ values and approach transparent to making well -27. inguidelinesdeveloped GRADEwith the etersen R, Akl R, EA, etersen al. DavoliM,et GRADE ineda with surveyrandomised on the canceandpresentation of Alonso-Coello Aal. health P, et guidefor on-determinantsrecommendation’sof a Mas G, DiezetMas AI,Valuesal. and Falck-Ytter Y, Falck-Ytter etGRADEal. 14.guidelines: . pohl JJ,Coello pohl al. PA, et GRADE zation Practices. MMWRzation 2011;60(RR- Page 48of63 Page 49of63 34 and included evidencein base for study designs, populations, 19 outcomes of interest (PICO 1) (PICOoutcomes of 1) interest interventions, or comparators 604 15 provide evidence matching

full

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Arthritis &Rheumatology John Wiley& Sons

AND = retrieves results that include all the the all include that results = retrieves AND search terms terms search

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NOT ((("COMMENT"[PUBLICATION TYPE]) OR OR TYPE]) NOT((("COMMENT"[PUBLICATION AND ("HUMANS"[MESH]))) AND("HUMANS"[MESH]))) NOT(("ANIMALS"[MESH]) (("ANIMALS"[MESH]) NOT TYPE])) "LETTER"[PUBLICATION OR TYPE]) "EDITORIAL"[PUBLICATION AND ("ADULT"[MESH])))) "INFANT"[MESH]) OR "CHILD"[MESH]) OR (((("ADOLESCENT"[MESH]) NOT "INFANT"[MESH]) OR Query SPONDYLITIS[TIAB] OR SPONDYLITIS OR SPONDYLITIS[TIAB] RHEUMATOID OR DISEASE[TIAB] BECHTEREWS OR DISEASE[TIAB] BECHTEREW'S OR DISEASE[TIAB] BECHTEREW OR ANKYLOPOIETICA[TIAB] SPONDYLARTHRITIS OR SPONDYLITIS ANKYLOSING OR SPONDYLARTHRIT*[TIAB] Accepted ANKYLOSING OR ANKYLOPOIETICA[TIAB] (SPONDYLOARTHRITIS OR ARTHROPATH*[TIAB]) PSORIATIC OR ARTHROPATHICA[TIAB] PSORIASIS OR ARTHRITIS[TIAB] PSORIATIC OR PSORIASIS[TIAB] (ARTHRITIC OR SYNDROME*[TIAB]) BECHTEREW OR STRUMPELLSPONDYLITIS[TIAB] MARIE OR STRUMPELLSPONDYLITIS[TIAB] (MARIE- OR SPONDYLARTHROPATH*[TIAB]) OR ("SPONDYLARTHROPATHIES"[MESH] OR (SPONDYLOARTHRITIS*[TIAB]) OR (SPONDYLARTHRITIS*[TIAB]) OR (("SPONDYLARTHRITIS"[MESH:NOEXP]) OR ONSET[TIAB])))) ADULT- OR ONSET[TIAB] AND(ADULT STILL'S DISEASE[TIAB]) OR DISEASE[TIAB] ((STILL OR DISEASE,ADULT-ONSET"[MESH]) ("STILL'S OR NODULE*[TIAB]) RHEUMATOID OR NODULE"[MESH] ("RHEUMATOID OR ARTHRITIS*[TIAB]) RHEUMATOID Article OR RHEUMATOID"[MESH:NOEXP] (("ARTHRITIS, OR ARTHRITIS*[TIAB]) ((INFLAMMATORY OR (LUPUS[TIAB])) OR (SLE[TIAB]) OR DISEASE[TIAB]) SACKS LIBMAN OR DISEASE[TIAB] LIBMAN-SACKS OR DISSEMINATUS[TIAB] ERYTHEMATOSUS LUPUS OR SYSTEMIC"[MESH]

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OR MALOPRIM[TIAB] OR MEFLOQUINE*[TIAB] MEFLOQUINE*[TIAB] OR MALOPRIM[TIAB] OR LUMEFANTRINE[TIAB] OR LAPACHOL[TIAB] OR HALOFANTRINE[TIAB] OR 64[TIAB] E OR DIHYDROARTEMISININ[TIAB] OR DERMASEPTIN[TIAB] OR DAPSONE[TIAB] OR CYCLOGUANIL[TIAB] OR CURDLAN SULFATE[TIAB] OR Accepted CRYPTOLEPINE[TIAB] OR CINCHONINE[TIAB] OR CHLORPROGUANIL[TIAB] AND BRL OR 6231[TIAB] BREDININ[TIAB] OR ACID[TIAB] BETULINIC OR ATOVAQUONE[TIAB] OR ARTESUNATE[TIAB] OR ARTEMOTIL[TIAB] OR ARTEMISININS[TIAB] OR ARTEMETHER*[TIAB] OR ARTEFLENE[TIAB] OR AMODIAQUINE[TIAB] OR AMARIIN[TIAB] OR ((ACEDAPSONE[TIAB] OR ARECHINE[TIAB]) OR ARALEN[TIAB] OR NIVAQUINE[TIAB] OR CHINGAMIN[TIAB] OR KHINGAMIN[TIAB] OR (((CHLOROCHIN[TIAB] OR BIOTHERAP*[TIAB]) OR THERAP*[TIAB] BIOLOGIC OR THERAP*[TIAB] BIOLOGICAL OR THERAPY"[MESH] ("BIOLOGICAL ARTHRITI*[TW])) AUTOIMMUNE (INFLAMMATORY OR ARTHRITIS[TW]) INFLAMMATORY OR JUVENILE STILLS DISEASE[TW] ONSET OR JUVENILE STILLS DISEASE[TW] ONSET OR JUVENILE- STILL'S DISEASE[TW] ONSET Article OR JUVENILE- DISEASE[TW] STILL ONSET OR JUVENILE DISEASE[TW] STILL ONSET OR JUVENILE- ARTHRITIS[TW] SYSTEMIC OR JUVENILE ARTHRITIS[TW] PSORIATIC OR JUVENILE JUVENILEOLIGOARTHRITIS[TW] OR ARTHRITIS[TW] IDIOPATHIC JUVENILE OR ARTHRITIS[TW] JUVENILECHRONIC OR ARTHRITIS[TW] ENTHESITIS-RELATED OR JUVENILE ARTHRITIS[TW] ((JUVENILE OR ARTHRI*[TIAB])) POSTINFECTIOUS OR DISEASE[TIAB] REITER OR DISEASE[TIAB] REITERS OR DISEASE*[TIAB] REITER'S OR SYNDROME*[TIAB] REITER OR ARTHRI*[TIAB] INFECTIOUS POST OR ARTHRI*[TIAB] POST-INFECTIOUS OR ARTHRITI*[TIAB] (REACTIVE OR ANKYLOPOIETICA[TIAB]) Query

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MYCOPHENOLATE MOFETIL[TW] OR RS RS OR MOFETIL[TW] MYCOPHENOLATE OR CONCEPT] MOFETIL"[SUPPLEMENTARY ("MYCOPHENOLATE OR ACID*[TW]) MYCOPHENOLIC OR ACID"[MESH] (("MYCOPHENOLIC OR SU101[TIAB])) OR HWA-486[TIAB] OR 486[TIAB] HWA Accepted OR ARAVA[TIAB] OR LEFLUNOMIDE*[TIAB] OR CONCEPT] ("LEFLUNOMIDE"[SUPPLEMENTARY OR DMARD*[TIAB]) OR RHEUMATIC[TIAB] ANTI OR RHEUMATIC[TIAB] ANTI- OR ANTIRHEUMATIC*[TIAB] OR AGENTS"[MESH] ("ANTIRHEUMATIC OR ACTION]) AGENTS"[PHARMACOLOGICAL ("ANTIRHEUMATIC OR PYRALIN OR EN[TIAB]) SALAZOPYRIN[TIAB] OR AZULFIDINE[TIAB] OR UCINE[TIAB] OR PLEON[TIAB] OR PLEON[TIAB] COLO OR PLEON[TIAB] COLO- OR SALAZOSULFAPYRIDINE[TIAB] OR SALICYLAZOSULFAPYRIDINE[TIAB] OR SULPHASALAZINE*[TW] OR SULFASALAZINE*[TW] OR ("SULFASALAZINE"[MESH] OR (((SULFASALAZINE) OR (TOFACITINIB*[TW]) OR 690,550[TIAB]) CP- OR 690550[TIAB] CP OR 690550[TIAB] CP- OR CP690550[TIAB] OR 690,550[TIAB] CP OR XELJANZ[TIAB] OR TASOCITINIB[TIAB] OR CONCEPT] ("TOFACITINIB"[SUPPLEMENTARY Article OR INCB028050[TIAB]) OR LY3009104[TIAB] OR BARICITINIB[TIAB] OR CONCEPT] ((("BARICITINIB"[SUPPLEMENTARY OR TRIMETHOPRIM[TIAB]) OR TETRANDRINE[TIAB] OR TAFENOQUINE[TIAB] OR SULFALENE[TIAB] OR SULFADOXINE[TIAB] OR SPIROGERMANIUM[TIAB] OR SINEFUNGIN[TIAB] OR PHTHALOCYANINE[TIAB] SILICON OR 538[TIAB] RV OR QUININE[TIAB] OR QUINIDINE[TIAB] OR PYRONARIDINE[TIAB] OR PYRIMETHAMINE[TIAB] OR PROGUANIL[TIAB] OR PRIMAQUINE[TIAB] OR PIPERAQUINE[TIAB] OR PEPSTATIN[TIAB] OR PARVAQUONE[TIAB] OR MONORDEN[TIAB] OR MIRINCAMYCIN[TIAB] OR Query

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PLAQUENIL[TIAB]) OR OR PLAQUENIL[TIAB]) OR OXYCHLOROQUINE[TIAB] OR HYDROXYCHLOROQUINE*[TIAB] OR ("HYDROXYCHLOROQUINE"[MESH] OR BELIMUMAB[TIAB]) OR CONCEPT] ("BELIMUMAB"[SUPPLEMENTARY Accepted OR RITUXAN[TIAB]) OR GP2013[TIAB] IDECOR C2B8[TIAB] OR IDEC-C2B8[TIAB] OR MABTHERA[TIAB] OR RITUXIMAB[TW] OR RITUXIMAB[TIAB] OR ("RITUXIMAB"[MESH] OR MEXATE[TIAB]) OR METHOTREXATE[TIAB] OR AMETHOPTERIN[TIAB] OR ("METHOTREXATE"[MESH] OR ("CYCLOPHOSPHAMIDE"[MESH]) OR CYTOXAN[TIAB]) OR B518[TIAB] OR B OR 518[TIAB] 518[TIAB] B- OR SENDOXAN[TIAB] OR PROCYTOX[TIAB] OR NSC26271[TIAB] OR 26271[TIAB] NSC OR NSC-26271[TIAB] OR NEOSAR[TIAB] OR ENDOXAN[TIAB] OR CYCLOPHOSPHANE[TIAB] OR (CYCLOPHOSPHAMIDE*[TIAB] OR FK506[TIAB]) OR FK OR 506[TIAB] 506[TIAB] FK- OR FR900506[TIAB] OR 900506[TIAB] FR OR FR-900506[TIAB] OR TACROLIMUS[TIAB] OR PROGRAFT[TIAB] OR PROGRAF[TIAB] OR ("TACROLIMUS"[MESH] OR 27400[TIAB]) OL OR OL 400[TIAB] 27 OR OL OR 27-400[TIAB] NEORAL[TIAB] CSA OR CSA-NEORAL[TIAB] OR Article SANDIMMUN[TIAB] OR SANDIMMUNE[TIAB] OR NOF[TIAB] CYA OR CYA-NOF[TIAB] OR NEORAL[TIAB] OR CYCLOSPORIN*[TW] OR CYCLOSPORINE*[TIAB] OR CYCLOSPORINS[MH] OR ("CYCLOSPORINE"[MESH] OR MIZORIBINE*[TIAB]) OR CONCEPT] ("BREDININ"[SUPPLEMENTARY OR IMMURAN[TIAB]) OR IMURAN[TIAB] IMUREL[TIAB]OR OR AZOTHIOPRINE[TIAB] OR AZATHIOPRINE[TIAB] OR ("AZATHIOPRINE"[MESH] (MMF[TIAB]) OR OR CELLCEPT[TW]) OR MYFORTIC[TW] OR MYCOPHENOLATE[TW] SODIUM OR SODIUM[TW] MYCOPHENOLATE OR RS-61443[TW] OR 61443[TW] Query

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NECROSIS FACTOR ANTAGONIST*[TIAB]) OR OR ANTAGONIST*[TIAB]) FACTOR NECROSIS FACTOR- NECROSIS PROTEIN*[TIAB] OR TNR-001[TIAB] OR TNR TNR OR TNR-001[TIAB] OR PROTEIN*[TIAB] TNFR FCFUSION OR PROTEIN*[TIAB] FUSION TNFR-FC OR PROTEIN*[TIAB] II IGGTYPE FUSION RECEPTOR TNF OR PROTEIN*[TIAB] IGGFUSION II- TYPE TNF RECEPTOR OR ENBREL[TIAB] OR Accepted ETANERCEPT[TIAB] OR ("ETANERCEPT"[MESH] OR HUMIRA[TIAB]) OR ANTIBOD*[TIAB] D2E7 OR ADALIMUMAB[TIAB] OR ("ADALIMUMAB"[MESH] OR ANTAGONIST*[TIAB]) FACTOR-ALPHA NECROSIS TUMOUR OR ANTAGONIST*[TIAB] FACTOR-ALPHA NECROSIS (TUMOR TUMOUR OR ANTAGONIST*[TIAB] FACTOR NECROSIS (TUMOR OR INHIBITORS"[MESH]) ("TUMOR OR INHIBITOR*[TIAB]) FACTOR NECROSIS TUMOR OR INHIBITOR*[TIAB] FACTOR NECROSIS TUMOUR OR INHIBITOR*[TIAB] TNF OR FACTOR*[TIAB] NECROSIS TUMOUR ANTI OR FACTOR*[TIAB] ANTI-TUMOUR OR NECROSIS FACTOR*[TW] ANTI-TUMOR OR NECROSIS FACTOR*[TW] ANTI OR NECROSIS TUMOR ANTITNF*[TW] OR (ANTI-TNF*[TW] OR BIOLOGIC[TI]) TNF (ANTI- OR CC-10004[TIAB]) OR 10004[TIAB] CC OR OTEZLA[TIAB] OR APREMILAST[TIAB] OR Article CONCEPT] ("APREMILAST"[SUPPLEMENTARY OR BMY28689[TIAB])) OR ATRIDOX[TIAB] OR VIBRAMYCIN[TIAB] OR VIBRA OR TABS[TIAB] VIBRA-TABS[TIAB] OR PERIOSTAT[TIAB] OR ORACEA[TIAB] OR HYDRAMYCIN*[TIAB] OR DORYX[TIAB] OR BU OR 3839T[TIAB] VIBRAVENOS*[TIAB] OR DEOXYOXYTETRACYCLINE*[TIAB] 6 ALPHA OR DEOXYOXYTETRACYCLINE*[TIAB] ALPHA-6- OR DOXYCYCLINE*[TIAB] OR ("DOXYCYCLINE"[MESH] OR CHLOROQUINE[TIAB]))) OR ("CHLOROQUINE"[MESH] OR QUINACRINE[TIAB]) OR ("QUINACRINE"[MESH] OR ACTION]) ("ANTIMALARIALS"[PHARMACOLOGICAL Query

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OR CLOBETASOL[TIAB] OR CLOBETASONE CLOBETASONE OR CLOBETASOL[TIAB] OR CICLESONIDE[TIAB] OR BUDESONIDE[TIAB] OR BETAMETHASONE[TIAB] OR BECLOMETHASONE[TIAB] OR AMCINONIDE[TIAB] OR DIPROPIONATE[TIAB] (ALCLOMETASONE OR ACTION]) Accepted ("GLUCOCORTICOIDS"[PHARMACOLOGICAL OR GLUCOCORTICOID*[TIAB]) OR ("GLUCOCORTICOIDS"[MESH] OR AIN-457[TIAB]) OR AIN457[TIAB] OR AIN 457[TIAB] OR COSENTYX[TIAB] OR SECUKINUMAB[TIAB] OR CONCEPT] ("SECUKINUMAB"[SUPPLEMENTARY OR KINERET[TIAB]) OR ANAKINRA[TIAB] OR ANTRIL[TIAB] IL-1RA[TIAB]OR OR INHIBITOR*[TIAB] IL-1URINE OR INHIBITOR*[TIAB] FEBRILE IL1 OR IL1INHIBITOR[TIAB] DERIVED URINE OR IL1INHIBITOR*[TIAB] URINE-DERIVED OR ANTAGONIST PROTEIN"[MESH] RECEPTOR 1 ("INTERLEUKIN OR ACTEMRA[TIAB]) OR ATLIZUMAB[TIAB] OR TOCILIZUMAB[TIAB] OR CONCEPT] ("TOCILIZUMAB"[SUPPLEMENTARY OR IMMUNOGLOBULIN*[TIAB]) 4 ANTIGEN ASSOCIATED LYMPHOCYTE T CYTOTOXIC OR IMMUNOGLOBULIN*[TIAB] 4- ANTIGEN LYMPHOCYTE-ASSOCIATED T CYTOTOXIC OR CTLA4-FC[TIAB] Article OR CTLA4-IG[TIAB] OR CTLA-4-LG[TIAB] OR 188667[TIAB] BMX OR ORENCIA[TIAB] OR NULOJIX[TIAB] OR LEA29Y[TIAB] OR 224818[TIAB] BMS OR BMS-224818[TIAB] OR BELATACEPT[TIAB] OR ABATACEPT[TIAB] OR ("ABATACEPT"[MESH] OR REMICADE[TIAB]) OR CA2[TIAB] ANTIBODY MONOCLONAL OR MAB CA2[TIAB] OR INFLIXIMAB[TIAB] OR ("INFLIXIMAB"[MESH] OR 870[TIAB]) CDP OR CDP870[TIAB] OR CIMZIA*[TIAB] OR PEGOL*[TIAB] CERTOLIZUMAB OR PEGOL"[MESH] ("CERTOLIZUMAB OR SIMPONI[TIAB]) OR GOLIMUMAB[TIAB] OR CONCEPT] ("GOLIMUMAB"[SUPPLEMENTARY OR PROTEIN*[TIAB]) FUSION TNF OR RECEPTOR 001[TIAB] Query

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Accepted CNTO1275[TIAB])) OR 1275[TIAB] CNTO OR STELARA[TIAB] OR USTEKINUMAB*[TIAB] OR ("USTEKINUMAB"[MESH] OR TRIAMCINOLONE[TIAB])))) OR RIMEXOLONE[TIAB] OR PREDNISONE[TIAB] OR PREDNISOLONE[TIAB] OR PREDNICARBATE[TIAB] OR PARAMETHASONE[TIAB] OR METHYLPREDNISOLONE[TIAB] OR ACETATE*[TIAB] MELENGESTROL OR MEDRYSONE[TIAB] OR FLUTICASONE[TIAB] Article OR FLURANDRENOLONE[TIAB] OR FLUPREDNISOLONE[TIAB] AND ACETATE*[TIAB] FLUPREDNIDENE OR ACETATE*[TIAB] FLUPEROLONE OR FLUOROMETHOLONE[TIAB] OR FLUOCORTOLONE[TIAB] OR BUTYLESTER[TIAB] FLUOCORTIN OR FLUOCINONIDE*[TIAB] OR ACETONIDE*[TIAB] FLUOCINOLONE OR FLUMETHASONE[TIAB] OR POTASSIUM[TIAB] PHOSPHATE DROCINONIDE OR DIFLUPREDNATE[TIAB] OR DIFLUCORTOLONE[TIAB] OR DIFLORASONE[TIAB] OR ACETATE[TIAB] DICHLORISONE OR DEXAMETHASONE[TIAB] OR DESOXIMETASONE[TIAB] OR CLOCORTOLONE[TIAB] OR BUTYRATE*[TIAB] Query

Boolean Operators Operators Boolean

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John Wiley& Sons etc. types, publication language, years, groups, age to results to limit = command LIM terms emtree narrower all to retrieve command = a EXP either direction direction either in other, each of words 2 within are terms = adj2 ; direction either in other, each

– March – 20166, retrieves results that include all the the all include that results retrieves acent to acent Page 8 Page8 #12 #12 #11 #10 #9 #8 #7 #6 #5 #4 #3 #2 'HIPARTHROPLASTY'/E OR 'KNEEARTHROPLASTY'/EXP #1 SearchStrategy: Database:Embase #15 #15 #14 #13 #13 [ENGLISH]/LIM OR 2010:PY 2011:PY OR OR 2012:PY 2013:PY OR 2014:PY OR 2003:PY 2004:PY OR OR 2005:PY 2006:PY OR 2007:PY OR 1996:PY 1997:PY OR OR 1998:PY 1999:PY OR 2000:PY OR 1989:PY 1990:PY OR OR 1991:PY 1992:PY OR 1993:PY OR 1982:PY 1983:PY OR OR 1984:PY 1985:PY OR 1986:PY (ARTHROPLAST*:DE,AB,TIOR REPLACEMENT*:DE,AB,TI OR PROSTHESES':AB,TI REPLACEMENT':AB,TI TOTAL 'KNEEOR PROSTHESIS':AB,TI REPLACEMENT':AB,TI PROSTHESIS':AB,TI'FEMORALHEAD OR PROSTHESES':AB,T PROSTHESIS':AB,TI'HIPPROSTHESES':AB,TIOR 'FEM OR ‘KNEE REPLACEMENT':AB,TI ‘KNEE 'KNEEOR ARTHROPLASTY':AB ‘HIP'HIPREPLACEMENT':AB,TI OR ARTHROPLASTY':AB,T #13 OR #13 #14

one of the search terms search terms terms search the search from terms of retrieval the = excludes NOT terms the search of one

'EDITORIAL'/EXP'LETTER'/EXPOR OR 'ABSTRACT REPORT 'CASEREPORT'/EXP #11 NOT #10 Accepted'ANIMAL'/EXP('ANIMAL'/EXP NOT 'HUMAN'/EXP)AND #9 NOT #6 AND NOT #7 (#7 #8) 'ADULT'/EXP 'JUVENILE'/EXP AND #5 [EMBASE]/LIM [MEDLINE]/LIM NOT AND (1980:PY OR #1 OR #2 OR #3 #4 KNEE*:DE,AB,TIOR ORHIP:DE,AB,TI HIPS:DE,AB,TI AND Article

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OR 2015:PY OR 2016:PY)AND OR 2008:PY OR OR 2009:PY OR 2001:PY OR OR 2002:PY OR 1994:PY OR OR 1995:PY OR 1987:PY OR OR 1988:PY ORALHEAD OR 'KNEEOR I'HIP TOTAL OR PROSTHES*:DE,AB,TI)

I'HIPOR OR1981:PY OR '/EXP ,TI OR 'KNEE,TI OR XP XP Page 9 Page9 Page 58of63 Page 59of63 MYCOPHENOLATE*:AB,TIOR MELBEX:AB,TI #30 #30 #29 #28 #27 #25 #24 #23 #22 #21 #20 #19 #18 #17 #16 #31 #31 'ANTI-MALARIALS':AB,TI MALARIAL':AB,TI'ANTI-MALARIAL':AB,TIOR 'ANTIOR M 'ANTI-RHEUMATICS':AB,TI RHEUMATIC':AB,TI'ANTIOR RHEUMATICS':AB,TI 'ANTOR 2 'RITUXIMAB'/EXPOR RITUXAN:AB,TI OR RITUXIMAB: #26 ZYTRIM:AB,TI THIOAZEPRINE:AB,TITHIOPRINE:AB,TI OR TRANSIMUNEOR IMURANE:AB,TIIMUREK:AB,TIOR IMUREL:AB,TIOR IMOR IMMUTHERA:AB,TIOR IMUNEN:AB,TIOR IMUPRIN:AB,TI OR AZOTHIOPRINE:AB,TIORCOLINSAN:AB,TI IMMURAN:AB, OR AZATRILEM:AB,TIAZOPI:AB,TIOR AZORAN:AB,TIOR OR A AZATHROPSIN:AB,TIAZATIOPRIN:AB,TI OR AZATOX:AB, OR AZATHIOPRIM:AB,TIAZATHIOPRIN:AB,TI OR OR AZATHIOPU AZASAN:AB,TIOR AZATHIODURA:AB,TI OR AZATHIOPINE:AB AZAPIN:AB,TIORAZAPRESS:AB,TI OR AZAPRINE:AB,TI OR AZAHEXAL:AB,TIOR AZAMEDAC:AB,TI OR AZAMUN*:AB,TI O MERCAPTOPURINE:AB,TIOR ARATHIOPRIN*:AB,TI OR AZAFA IMPLANTA:AB,TIIMUSPORIN:AB,TIOR HYDROXYCHLOROQUINE*:AB,TI

'ANTIRHEUMATICOR AGENT'/EXP ANTIRHEUMATIC*:AB,TI O 'GLUCOCORTICOID'/EXPOR GLUCOCORTICOID*:AB,TI #15 NOT #12 'LEFLUNOMIDE'/EXPARAVA:AB,TI OR OR LEFLUNOMIDE:AB, 'MEPACRINE':AB,TIQUINACRINE:AB,TIOR CHROLOQUINOR 'ANTIMALARIALOR ANTIMALARIAL*:AB,TI AGENT'/EXP OR 'BELIMUMAB'/EXPOR BENLYSTA:AB,TI B' 'LYMPHOSTAT OR 'METHOTREXATE'/EXP ORMETHOTREXATE*:AB,TI OR RHEUMA 'CYCLOPHOSPHAMIDE'/EXPOR CYCLOPHOSPHAMIDE*:AB,TI 'TACROLIMUS'/EXPTACROLIMUS:AB,TIOR PROGRAF:AB, OR 'CYCLOSPORIN'/EXPCYCLOSPORIN*:AB,TI OR ORDEXIMUNE 'MIZORIBINE'/EXPMIZORIBINE:AB,TIOR BREDININ:ABOR 'AZATHIOPRINE'/EXPOR AZATHIOPRINE*:AB,TI OR

Accepted'HYDROXYCHLOROQUINE'/EXPOR PLAQUENIL:AB,TI OR Article'MYCOPHENOLIC'MMF':AB,TIOR ACID'/EXP MYFORTIC: OR

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons ALARIALS':AB,TIOR I-RHEUMATIC':AB,TIOR AZAREX:AB,TI OR ZOTHIOPRIN:AB,TIOR UREN:AB,TIOR OR IMURAN:AB,TIOR OR TIOR :AB,TI OR :AB,TIOR AB,TI TIIMMUREL:AB,TIOR RINE:AB,TIOR ,TIOR LK:AB,TIOR RAZANIN:AB,TI OR ,TI ,TI AB,TIOR E*:AB,TI E*:AB,TI :AB,TI :AB,TI 'ANTI TI TI TI TI :AB,TI OR OR :AB,TI R 'ANTIR TREX:AB,TI Page 10 Page10 #48 #48 #47 #46 #45 #44 #43 #41 #40 #39 #38 #37 #36 #35 #34 #33 'DISEASEANTIRHEUMATICMODIFYING OR DRUG'/EXP DMARDS:AB,TI #32 4 #49 4 'INFLIXIMAB'/EXPOR REMICADE:AB,TI INFLIXIMOR #42 PEGOL':AB,TI EMBREL:AB,TI ANTAGONIST':AB,TI'TUMOUR OR NECROSISANTAGO FACTOR ANTAGONIST':AB,TI'TNF OR ANTAGONISTS':AB,TI 'TUOR INHIBITOR':AB,TI'TUMOUR NECROSISOR INHIBIT FACTOR INHIBITOR':AB,TI'TNF'TNF ORINHIBITORS':AB,TI OR NECROSISTUMOR FACTOR':AB,TI 'ANTIOR NECROSTUMOUR XELJANZ:AB,TI ROACTEMRA:AB,TITOCILIZUMAB:AB,TIOR APREMILAST:AB,TI MONODOX:AB,TIOR 'VIBRA-TABS':AVIBRAMYCIN:AB,TI OR ANAKINRA:AB,TI OR KINERET:AB,TI ADALIMUMAB:AB,TI SALICYLAZOSULFAPYRIDIN:AB,TI SALAZOSULFAPYRIDINE*:AB,TIOR SULFASALAZINE*:AB,TI

'TOFACITINIB'/EXPOR TOFACITINIB:AB,TI TASOCITINOR 'DOXYCYCLINE'/EXPOR DORYX:AB,TI OR DOXYCYCLINE*:AB 'USTEKINUMAB'/EXPOR STELARA:AB,TI OR USTEKINUMAB:A 'SECUKINUMAB'/EXPOR COSENTYX:AB,TI OR SECUKINUMAB: 'RECOMBINANTINTERLEUKIN RECEPTOR 1 BLOCKING AGENT' 'TOCILIZUMAB'/EXPOR ACTEMRA:AB,TI OR ATLIZUMAB:AB, 'ABATACEPT'/EXPOR ORENCIA:AB,TI ORABATACEPT:AB,TI 'TUMOR NECROSISINHIBITOR'/EXP FACTOR 'ANTIOR TNF' 'CERTOLIZUMABOR CIMZIA:AB,TI PEGOL'/EXP 'CERTOLOR 'GOLIMUMAB'/EXPOR SIMPONI:AB,TI GOLIMUMAB:AB,TIOR 'ETANERCEPT'/EXPOR ENBREL:AB,TI OR ETANERCEPT:AB,T 'ADALIMUMAB'/EXPHUMIRA:AB,TI OR OR TRUDEXA:AB,TI O 'APREMILAST'/EXPOR ACETAMIDE:AB,TIOTEZLA:AB,TI OR 'BARICITINIB'/EXPOR BARICITINIB:AB,TI

'BIOLOGICALTHERAPY'/EXP Accepted Article 'SALAZOSULFAPYRIDINE'/EXPOR AZULFIDINE:AB,TI OR

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons 'TUMOUR NECROSISFACTOR MOR NECROSISFACTOR ORS':AB,TI OR 'TNFOR ORS':AB,TI AB:AB,TI B,TI B,TI OROR SSZ:AB,TI ISFACTOR':AB,TI OR DMARD:AB,TIOR NIST':AB,TI IB*:AB,TI OR :AB,TI OR 'ANTIOR:AB,TI OR IZUMAB

IOR

TIOR R B,TI B,TI ,TIOR AB,TI AB,TI /EXP OR/EXP Page 11 Page11 Page 60of63 Page 61of63 'RHEUMATOIDSPONDYLITIS':AB,TI 'SPONDYLITISOR ANKY SPONDYLARTHRITIS':AB,TI'SPONDYLARTHRITISOR ANKYLO 'PSORIATICARTHROPATHY':AB,TI 'PSORIATICOR ARTHROP 'PSORIATICARTHRITIS':AB,TI 'PSORIASISOR ARTHROPAT #69 #69 ‘ #68 #67 #66 #65 #64 #63 #62 #61 #60 #59 #58 #57 #56 #55 #54 #53 #51 #50 #70 #69 AND #50 AND #16 AND#16 AND#50 #69 #70 5 'ANKYLOSING'ANKYLOSINGSPONDYLITIS'/EXP OR SP #52 'LIBMAN-SACKSOR DISEASE':AB,TI 'LIBMANOR DISACKS 'INFLAMMATORYARTHRITIS':AB,TI OR OR #39 OR #40 #41 #42 OR OR OR #43 #44 #45 OR #4 OROR OR #28 OR #29 #30 OR OR #31 OR #32 #33 OR #34 OROR OR #62 OR #63 #64 OR #65 #66 INFECTIOUSARTHRITIS':AB,TI 'POSTINFECTIOUSOR ARTH SPONDYLOARTHRITISANKYLOPOIETICA':AB,TI 'ANKYLOOR

'SPONDYLARTHRITIS'/EXPOR SPONDYLARTHRIT*:AB,TI 'SYSTEMICLUPUS ERYTHEMATOSUS'/DE 'SLE':AB,TIOR OR OR OR #17 OR #18 #19 #20 OR OR OR #21 #22 #23 OR #2 #68 OR #68 #67 OR OR #51 OR #52 #53 #54 OR OR OR #55 #56 #57 OR #5 'STILLS'STILLORDISEASE':AB,TI DISEASE':AB,TI 'ADULTSTILL ONSET DISEASE':AB,TI 'RHEUMATOID NODULE':AB,TI'RHEUMATOIDOR NODULES':A 'RHEUMATOIDARTHRITIS'/EXPOR 'RHEUMATOID ARTHRITIS 'REITEROR SYNDROME'/EXP REITER:DE,AB,TI 'REACTIVEARTHRITIS'/EXP OR 'REACTIVE ARTHRITIS':AB BECHTEREW*:AB,TI 'MARIESPONDYLITIS':AB,TI STRUMPELL 'SPONDYLOARTHROPATHY'/EXP SPONDYLARTHROPATH*:DE,AB,TI SPONDYLOARTHRIT*:AB,TI 'PSORIATIC'ARTHRITICARTHRITIS'/EXPOR PSORIASIS':

JUVENILERHEUMATOID ARTHRITIS'/EXP 'JUVENILEOR ART Accepted Article

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons 6 OR 6 OR #47 #48 OR #49 #35 OR OR #35 #36 #37 OR OR #38 HICA':AB,TIOR SEASE':AB,TI SEASE':AB,TI RITIS':AB,TI RITIS':AB,TI 4 OR 4 OR #25 #26 OR #27 8 OR 8 OR #59 #60 OR #61 ATHIES':AB,TI LOPOIETICA':AB,TI ONDYLITIS':AB,TI ONDYLITIS':AB,TI POIETICA':AB,TIOR AB,TI OR ,TI'POST- OR 'LUPUS':AB,TI HRITIS':AB,TI SING ':AB,TIOR B,TI B,TI Page 12 Page12 perioperatively (stress-doseperioperatively corticosteroids)c vs. or SLE independent SLE or theanti-rheumaticofof use med What is is background What the adverse for risk eventsasso TKAwho notor were thedrugsof receiving interest QUESTION 6: Baselinerisk events ofadverse pat in forand RA,meta-analyses and JIA,SpA, and includi the candidate outsidethe drugs the of settingsurgical foris risk What the serious adverse events,infect QUESTION Indirect 5: evidence ofdrug-related adver or more ofmore candidate or the drugs one inwhom deci has withAS, In RA, patients or notPsA,JIA,severe se 2PICO continuing? or onetheof more candidate drugs,is what the eff withAS, In RA, patients or notPsA,JIA,severe se 1PICO SUPPLEMENTARYAPPENDIX Population, 3: Intervention, or more ofmore candidate or the drugs one inwhom deci has withAS, In RA, patients or notPsA,JIA,severe se 3PICO earlydrug priorthe versussurgery to stopping lat chronicglucocorticoids, whatthe is effect admi of withAS, In RA, patients or notPsA,JIA,severe se 4PICO earlydrug afterthe surgery versus late restarting

Accepted Article

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons ontinuingusualglucocorticoid the dose? vereundergoing SLE THA or TKA onare who receiving vereundergoing SLE THA or TKA andare who receivin vereundergoing SLE THA or TKA onare who receiving vereundergoing SLE THA or TKA are who receiving ions, hospitalizations, associatedor ofwith use e ? e? nisteringsupra-physiologic doses glucocorticoidof , limiting , the search systematic to literature revi ect drugstoppingof the priorto versussurgery ng observational studiesng observational in SLE,indicated? as ciated with orTHA TKA inRA,patients JI with SpA, ientswith inflammatoryarthritisundergoing THA icationsinterest?of

dedstopdrug, to the what iseffect stoppinthe of dedstopdrug, to the what iseffect the of restart se effectsfrom se non-surgical studies Comparator, Outcome (PICO)Questions achof ews s s ing A, A, e g e g Page 62of63 Page 63of Susan Goodman, SusanGoodman, (Hospital MD forSurgery/CorSpecial Leadership Core Team SUPPLEMENTARYAPPENDIX Teams 2: Involved Chicago, IL), Stryker, Chicago, Louis (University MD, Tex of forSpecial (Hospital Surgery/Cornell, New NY York, NY),Medicine,New York, A. Michael Mont, (CleveMD Fontana,Permanente, CA), A. Lisa Mandl, (HMPH MD, BeverlyJohnson, NY), (AlbertMD Einstein College o GA) (Atlanta, (AmericanMPH MD, College ofRheumatology, Atlanta, Singer, MD (UniversitySinger,MD of AnnMichigan, Arbor, MI), Orleans, New LA), Michael George, (UniversityMD of Abdel,PI), Matthew P. Clinic,MD (Mayo Rochester, Adolph Review Team PI), Yates, (UniversityMD of Pi Singh, Jasvinder MBBS, MPH Alabama (University of a LiteratureReview Team University,McMaster Hamilton, Ontario Consu(GRADE (UniversityMD Pittsburgh, of Pittsburgh, Co-Li PA; Alabama (University at of Birmingham, Birmingham,A (OrthoCarolinaMD Hip and KneeCenter,Charlotte, N

Accepted Article

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons as as MedicalGalveston,Branch, TX), Marat Turgunbaev teratureReviewTeam Gordon PI), Guyatt, MD, ), Scott ), Sporer, (MidwestMD atOrthopaedics Rush, f Medicine,Bronx,NY), Steve Lee, DO (Kaiser Jon Giles, MD, (ColumbiaMPH New University, York, MN),Vinod (LouisianaDasa, MD State University, ttsburgh, Pittsburgh, Co-LiteratureReviewPA; Team Pennsylvania, Philadelphia, Gewurz- PA), Ora C; Co-Project Jasvinder C; PI), Singh, MBBS, MPH tBirmingham,Birmingham, Co-Literature AL; L; Co-Literature L; Review Adolph Team PI), Yates, landCleveland,Clinic, Sculco,OH), Peter MD nell, New NY;New nell, Co-ProjectYork, Bryan Springer, PI), ospital forSpecial ospital Surgery/Weill Cornell ltant) GA), Janet GA), M.BSN, Waters, CWCNRN,MLS, , ,

Institute, Jefferson Institute, Thomas Hospital, University Ph Brause, (HospitalMD forSpecial Surgery/Cornell, N Springer, Bryan (OrthoCarolinaMD Hip andKnee Cent SusanGoodman, (Hospital MD forSurgery/CorSpecial Panel Voting MSW(GlobalPhD, Healthy Foundation, UpperLiving N Baltimore, University, MD), Eric (Mayo MD Matteson, Goodman, MD, (StanfordPhD University, Stanford, CA Rochester,MN), MarkFiggie, MD, MBA (Hospitalfor AnneBass, (Hospital MD for Surgery/CornellSpecial Panel Expert Fremont,Restoration, CA) Surgery/Cornell,Special NY),New York, Alexander S MSPH(UniversityMikuls, MD, Nebraska of MedicalCe Center, Nebraska Medical NE, andOmaha, National Da MacKenzie, (HospitalMD forSpecial Surgery/Cornell New Surgery/Cornell, York,Elena NY), Losina, ( PhD ANP Rosenblatt, (Rockefeller University, New York, Salt Utah, City,UT),Lake MarkGoodman, (Univer MD

Accepted Article

This article isprotected by copyright. All rights reserved. Arthritis &Rheumatology John Wiley& Sons iladelphia,PA),Jeremy Gililland, (UniversityMD o ew York, NY), ewYork, Antonia F.Chen, MBA MD, (Rothman BrighamandHospital,Women’s Boston, MA),Ronald NY),KyriakosKirou, (HospitalMD forSpecial ah,(Dearborn-SahMD Institute forJoint , New , York, NY), Elie Berbari, (MayoClinic,MD , , York, NY), New Kaleb Michaud,(UniversityPhD of SpecialSurgery/Cornell, NY),New York, Stuart Rochester,Clinic, Benjamin Nowell, MN), William sity of Pittsburgh, Arlene Pittsburgh,Hurley- PA), er, Charlotte, NC;er, Co-Voting BarryPanel Leader), ), MarcHochberg, ), (JohnsMPH MD, Hopkins nter, Omaha,NE), Russell,Linda MD (Hospitalfor nell, New NY;New nell, Co-VotingYork, Panel Leader), yack, NY)yack, ta Bank for Bank ta Rheumatic Diseases,Wichita, KS), Ted f Page 64of63