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Management of Rheumatoid ArthritisPublished by:Malaysia Health Technology Assessment Section (MaHTAS)Medical Development Division, Ministry of Health MalaysiaLevel 4, Block E1, Precinct 1Federal Government Administrative Centre62590 Putrajaya, MalaysiaCopyrightThe copyright owner of this publication is MaHTAS. Content may bereproduced in any number of copies and in any format or mediumprovided that a copyright acknowledgement to MaHTAS is included andthe content is not changed, not sold, nor used to promote or endorseany product or service, and not used in an inappropriate or misleadingcontext.ISBN: 978-967-2173-82-3Available on the following rg.myhttp://www.msr.my/Also available as an app for Android and IOS platform: MyMaHTASSTATEMENT OF INTENTThese clinical practice guidelines (CPG) are meant to be guides forclinical practice, based on the best available evidence at the time ofdevelopment. Adherence to these guidelines may not necessarilyguarantee the best outcome in every case. Every healthcare provider isresponsible for the management of his/her unique patient based on theclinical picture presented by the patient and the management optionsavailable locally.

Management of Rheumatoid ArthritisUPDATING THE CPGThese guidelines were issued in 2019 and will be reviewed in a minimumperiod of four years (2023) or sooner if there is a need to do so. Whenit is due for updating, the Chairman of the CPG or National Advisor ofthe related specialty will be informed about it. A discussion will be doneon the need for a revision including the scope of the revised CPG. Amultidisciplinary team will be formed and the latest systematic reviewmethodology used by MaHTAS will be employed.Every care is taken to ensure that this publication is correct in everydetail at the time of publication. However, in the event of errors oromissions, corrections will be published in the web version of thisdocument, which is the definitive version at all times. This version canbe found on the websites mentioned above.

Management of Rheumatoid ArthritisTABLE OF CONTENTSNo.TitleKey RecommendationsLevels of Evidence and Formulation of RecommendationGuidelines Development and ObjectivesDevelopment GroupReview CommitteeExternal ReviewersAlgorithm 1. Diagnosis of Rheumatoid ArthritisAlgorithm 2. Treatment of Rheumatoid INICAL FEATURES23.INVESTIGATIONS3.1 Laboratory Test3.2 Imaging3.2.1 Plain Radiography3.2.2 Musculoskeletal Ultrasound3.2.3 Magnetic Resonance Imaging4455674.CLASSIFICATION CRITERIA85.PROGNOSTIC FACTORS96.REFERRAL7.10TREATMENT7.1 Non-Pharmacological Treatment7.1.1 Patient Education7.1.2 Occupational Therapy7.1.3 Physiotherapy7.1.4 Podiatry7.1.5 Dietetics7.2 Pharmacological Treatment7.2.1 Non-Steroidal Anti-Inflammatory Drugs7.2.2 Corticosteroids7.2.3 Disease Modifying Anti-Rheumatic Drugsa. Conventional Synthetic DMARDsb. Targeted Synthetic DMARDsc. Biologicsd. TIONAL AND COMPLEMENTARY MEDICINES

Management of Rheumatoid ArthritisTABLE OF CONTENTSNo.9.TitleRHEUMATOLOGY NURSE-LED CAREPage2610. SPECIAL CONSIDERATIONS10.1 Co-morbidity10.2 Pregnancy and Lactation10.3 Vaccination2727272811. MONITORING AND FOLLOW-UP2912. IMPLEMENTING THE GUIDELINES29REFERENCES31Appendix 1 Examples of Search StrategyAppendix 2 Clinical QuestionsAppendix 3 Outcome MeasuresAppendix 4 Patient Information LeafletAppendix 5 Principles of Joint ProtectionAppendix 6 Pharmacological Treatment ofRheumatoid ArthritisAppendix 7 Drug MonitoringAppendix 8 Tuberculosis Workup Priorto Biologic Therapy in Rheumatoid Arthritis363738414548List of AbbreviationsAcknowledgementDisclosure StatementSource of Funding586060605357

Management of Rheumatoid ArthritisKEY RECOMMENDATIONSThe following recommendations were highlighted by the CPGDevelopment Group as the key clinical recommendations that shouldbe prioritised for implementation.Diagnosis and Investigation Consider rheumatoid arthritis if inflammation involving multiple jointsis present for at least six weeks. Inflammatory markers and rheumatoid factor anti-citrullinatedpeptide antibody should be tested when there is clinical suspicion ofrheumatoid arthritis.Referral All patients suspected of having rheumatoid arthritis (RA) should bereferred to the rheumatologist. All RA patients should be primarily managed by rheumatologists. Co-management plan with primary healthcare providers may beoffered subsequently.Treatment Aim to achieve a state of clinical remission or at least low diseaseactivity within six months using a treat-to-target strategy in rheumatoidarthritis. Patient education should be included in the management ofrheumatoid arthritis. Short term low-dose corticosteroids may be used in active rheumatoidarthritis. Methotrexate should be used as the first-line Disease ModifyingAnti-Rheumatic Drug in all patients with rheumatoid arthritis unlesscontraindicated.i

Management of Rheumatoid ArthritisLEVELS OF EVIDENCELevelStudy designIEvidence from at least one properly randomised controlled trialII-1Evidence obtained from well-designed controlled trials withoutrandomisationII-2Evidence obtained from well-designed cohort or case-controlanalytic studies, preferably from more than one centre orgroupII-3Evidence from multiple time series with or without intervention;dramatic results in uncontrolled experiments (such as theresults of the introduction of penicillin treatment in the 1940s)could also be regarded as this type of evidenceIIIOpinions of respected authorities based on clinical experience;descriptive studies and case reports; or reports of expertcommitteesSOURCE: US / CANADIAN PREVENTIVE SERVICES TASK FORCE 2001FORMULATION OF RECOMMENDATIONIn line with new development in CPG methodology, the CPG Unit ofMaHTAS is adapting Grading Recommendations, Assessment,Development and Evaluation (GRADE) in its work process. Thequality of each retrieved evidence and its effect size are carefullyassessed/reviewed by the CPG Development Group. In formulatingthe recommendations, overall balances of the following aspects areconsidered in determining the strength of the recommendations: overall quality of evidence balance of benefits versus harms values and preferences resource implications equity, feasibility and acceptabilityii

Management of Rheumatoid ArthritisGUIDELINES DEVELOPMENT AND OBJECTIVESGUIDELINES DEVELOPMENTThe members of the Development Group (DG) for these CPG werefrom the Ministry of Health (MoH), Ministry of Education (MoE) andprivate sector. There was active involvement of a multidisciplinaryReview Committee (RC) during the process of the CPG development.A systematic literature search was carried out using the followingelectronic databases/platforms: mainly Medline via Ovid andCochrane Database of Systemic Reviews and others e.g. Pubmedand Guidelines International Network (G-I-N). Refer to Appendix 1 forExample of Search Strategy. The inclusion criteria were all patientswith rheumatoid arthritis regardless of study design. The search waslimited to literature published in the last 15 years and on humans andin English. In addition, the reference lists of all retrieved literature andguidelines were searched and experts in the field contacted to identifyrelevant studies. All searches were conducted from 29 May 2017 to 2June 2017. Literature search was repeated for all clinical questions atthe end of the CPG development process allowing any relevant paperspublished before 31 January 2019 to be included. Future CPG updateswill consider evidence published after this cut-off date. The detailsof the search strategy can be obtained upon request from the CPGSecretariat.Reference was also made to other guidelines as listed below: Rheumatoid Arthritis in Adults: Management [National Institute forHealth and Clinical Excellence (NICE), July 2018] Management of Early Rheumatoid Arthritis [Scottish IntercollegiateGuidelines Network (SIGN), February 2011]The CPGs were evaluated using the Appraisal of Guidelines forResearch and Evaluation (AGREE) II prior to being used as reference.A total of seven main clinical questions were developed under differentsections. Members of the DG were assigned individual questionswithin these sections. Refer to Appendix 2 for Clinical Questions.The DG members met 19 times throughout the development of theseguidelines. All literatures retrieved were appraised by at least two DGmembers using Critical Appraisal Skill Programme checklist, presentedin evidence tables and further discussed in each DG meetings. Allstatements and recommendations formulated after that were agreedupon by both the DG and RC. Where evidence was insufficient, therecommendations were made by consensus of the DG and RC. Anydifferences in opinion were resolved consensually. The CPG wasbased largely on the findings of systematic reviews, meta-analyses andclinical trials, with local practices taken into consideration.iii

Management of Rheumatoid ArthritisThe literatures used in these guidelines were graded using the US/Canadian Preventive Services Task Force Level of Evidence (2001)while the grading of recommendation was done using the principles ofGRADE (refer to the preceding page). The writing of the CPG followsstrictly the requirement of AGREE II.On completion, the draft CPG was reviewed by external reviewers. Itwas also posted on the MoH Malaysia official website for feedback fromany interested parties. The draft was finally presented to the TechnicalAdvisory Committee for CPG, and the Health Technology Assessment(HTA) and CPG Council, MoH Malaysia, for review and approval. Detailson the CPG development by MaHTAS can be obtained from Manual onDevelopment and Implementation of Evidence-based Clinical PracticeGuidelines published in 2015 (available at http://www.moh.gov.my/penerbitan/mymahtas/CPG MANUAL MAHTAS.pdf)iv

Management of Rheumatoid ArthritisOBJECTIVESThe objectives of the CPG are to provide evidence-based recommendations inrheumatoid arthritis (RA) based on the following aspects: diagnosis investigations treatment (non-pharmacological and pharmacological) special considerations referral and follow-upCLINICAL QUESTIONSRefer to Appendix 2.TARGET POPULATIONInclusion Criteria All patients with RA (16 years and above)Exclusion criteria Juvenile-onset Idiopathic ArthritisTARGET GROUP/USERThis CPG is intended to guide those in primary, secondary or tertiary care whoare involved in management of RA: doctors allied health professionals trainees and medical students policy makers patients and their advocates professional societiesHEALTHCARE SETTINGSPrimary, secondary or tertiary carev

Management of Rheumatoid ArthritisDEVELOPMENT GROUPChairpersonDatin Dr. Asmahan Mohamed IsmailConsultant RheumatologistHospital Raja Perempuan Zainab II, KelantanMembers (in alphabetical order)Dr. Asmah MohdConsultant RheumatologistHospital Sultanah Nur Zahirah,TerengganuDr. Mohd. Aminuddin Mohd. YusofHead of CPG Unit & Public HealthPhysicianHealth Technology Assessment SectionMinistry of Health Malaysia, PutrajayaDr. Chong Chin EuMs. Noornazli Zahirah AbdullahPharmacistPrincipal Assistant DirectorHealth Technology Assessment Section Hospital Putrajaya, PutrajayaMinistry of Health Malaysia, PutrajayaDr. Chong Hwee ChengConsultant RheumatologistHospital Melaka, MelakaDr. Norhaslira Abdul RahimFamily Medicine SpecialistKlinik Kesihatan Sg. Besi, Kuala LumpurMs. Chu Ai ReenOccupational TherapistHospital Tuanku Ja’afar,Negeri SembilanDr. Shereen Ch’ng SuyinConsultant RheumatologistHospital Selayang, SelangorDr. Habibah Mohamed YusoofConsultant RheumatologistHospital Selayang, SelangorDr. Tan Bee EngConsultant RheumatologistGleneagles Penang, Pulau PinangDr. Hazlyna BaharuddinLecturer & Consultant RheumatologistFaculty of MedicineUniversiti Teknologi MARA, SelangorDr. Zil Azwan AbdullahFamily Medicine SpecialistKlinik Kesihatan Presint 9, PutrajayaDr. Liza Mohd IsaConsultant RheumatologistHospital Putrajaya, Putrajayavi

Management of Rheumatoid ArthritisREVIEW COMMITTEEThe draft CPG was reviewed by a panel of experts from both publicand private sectors. They were asked to comment primarily on thecomprehensiveness and accuracy of the interpretation of evidencesupporting the recommendations in the CPG.ChairpersonDr. Mollyza Mohd. ZainSenior Consultant Rheumatologist(National Head of Clinical Service Rheumatology)Hospital Selayang, SelangorMembers (in alphabetical order)Dato’ Dr. Azmillah Hj. RosmanSenior Consultant RheumatologistHospital Selayang, SelangorDr. Hjh. Rosaida Hj. Md. SaidConsultant Gastroenterologist & HepatologistHospital Ampang, SelangorDr. Chow Sook KhuanConsultant RheumatologistSunway Medical Centre, SelangorAssoc. Prof. Dr. Sargunan SockalingamLecturer & Consultant RheumatologistUniversiti Malaya, Kuala LumpurMs. Ding Mee HongPatient AdvocateDr. Siti Aminah Akbar MericanConsultant Family Medicine SpecialistKlinik Kesihatan Batu Rakit, TerengganuDato’ Dr. Gun Suk ChynSenior Consultant RheumatologistHospital Tuanku Ja’afar,Negeri SembilanMs. Siti Rabi’atul ‘Adawiyah NasriPharmacistHospital Tuanku Ja’afar, Negeri SembilanDr. Junainah SabirinDr. Yoong Kar YawHead of Department & State PhysicianDeputy DirectorHealth Technology AssessmentHospital Sultan Ismail, JohorSectionMinistry of Health Malaysia, Putrajayavii

Management of Rheumatoid ArthritisEXTERNAL REVIEWERS (in alphabetical order)The following external reviewers provided feedback on the draft:Mr. Ang Yu JoePharmacistHospital Selayang, SelangorDr. Rozita ZakariaConsultant Family Medicine SpecialistKlinik Kesihatan Presint 18, PutrajayaDr. Foo Meng HowGeneral PractitionerKlinik Foo Sdn. Bhd., KelantanDatuk Dr. Sheikh Mohd. Amin SheikhMubarakDean of Graduate Studies & FamilyMedicine SpecialistAcademy of Family Physicians ofMalaysia (AFPM)Adj. Prof. Dr. Geoffrey O. LittlejohnConsultant RheumatologistMonash University, AustraliaMs. Tan Foo LanOccupational TherapistHospital Tengku Ampuan Rahimah,SelangorAdj. Prof. Dr. Koh Ee TzunConsultant RheumatologistTan Tock Seng Hospital, SingaporeDatuk Dr. Tarmizi Thayaparan AbdullahPart-time LecturerInternational Medical University,Negeri SembilanProf. Dr. Mohd Shahrir Mohamed SaidConsultant RheumatologistUniversiti Kebangsaan MalaysiaDr. Yeap Swan SimConsultant RheumatologistSubang Jaya Medical Centre, SelangorProf. Dr. Rohini HandaSenior Consultant RheumatologistIndraprastha Apollo Hospitals, IndiaDr. Yoon Chee KinConsultant PhysicianHospital Pulau Pinang, Pulau Pinangviii

Management of Rheumatoid ArthritisALGORITHM 1. DIAGNOSIS OF RHEUMATOID ARTHRITISInflammatory joint symptoms and/orpositive serology (RF onof talultrasoundYesSynovitisdetected?No Reassurance Consider o Inflammatoryarthritis forclose monitoring*presence of a first-degree relative with RA, raised inflammatory markers andextra-articular featuresACPA: anti-citrullinated peptide antibodyACR/EULAR: American College of Rheumatology/European League AgainstRheumatismRA: rheumatoid arthritisRF: rheumatoid factorModified:1. D’Agostino MA, Terslev L, Wakefield R, et al. Novel algorithms for the pragmaticuse of ultrasound in the management of patients with rheumatoid arthritis: fromdiagnosis to remission. Ann Rheum Dis. 2016 Nov;75(11):1902-1908.2. van Steenbergen HW, Aletaha D, Beaart-van de Voorde LJ, et al. EULAR definitionof arthralgia suspicious for progression to rheumatoid arthritis. Ann Rheum Dis.2017;76(3):491-496.ix

Management of Rheumatoid ArthritisALGORITHM 2. TREATMENT OF RHEUMATOID ARTHRITISFulfilled classification criteria of mentFirst LinePatient Education Disease information Medications Lifestyle modificationConventional syntheticDMARDsSecond LineAllied Health Care Physiotherapy Occupational therapyBiologic DMARDsorTargeted syntheticDMARDsNurse-led CareDMARDs: Disease Modifying Anti-Rheumatic DrugsNSAIDs: Non-Steroidal Anti-Inflammatory DrugsRA: Rheumatoid ArthritisxAdd-on therapy NSAIDs Corticosteroids

Management of Rheumatoid Arthritis1. INTRODUCTIONRheumatoid arthritis (RA) is a chronic and progressive autoimmunedisease which primarily affects the joints. It is characterised byuncontrolled proliferation of synovial tissue and a wide array ofmultisystem co-morbidities. The disease has an insidious onsetwith unpredictable and variable courses. Typically, RA manifestsas symmetrical polyarthritis but may also present with non-specificsymptoms e.g. fatigue, malaise and mild fever. Bone erosion,destruction of cartilage and complete loss of joint integrity can occurover time if treatment is delayed or inadequate.Numerous multicentre international studies have shown that diseaseprogression can be minimised with early and appropriate treatment.Treatment paradigm of RA has evolved over the last two decades withthe advent of biologics and implementation of treat-to-target (T2T)strategy.The Malaysian National Inflammatory Arthritis Registry (NIAR) reportedthat there is often a delay in RA diagnosis as only about 50% of casesare diagnosed within a year of the symptom onset. This may be due toa lack of awareness and understanding of the disease among publicand healthcare providers. Furthermore, limited human, financial andinfrastructure resources may also contribute to the difficulty of accessingrheumatology care.4This is the first national CPG on the management of RA aimed toincrease awareness among healthcare providers on the importance ofrecognizing early RA, timely referral to rheumatologist and initiation oftreatment. We hope that this CPG will foster close collaboration betweenvarious stakeholders in providing evidence-based management of RAto improve outcomes and ultimately patients’ quality of life (QoL).1

Management of Rheumatoid Arthritis2. CLINICAL FEATURESClinical features of RA can be divided into articular and extra-articularmanifestations. Extra-articular features may involve multiple organsincluding the skin, eyes, lungs and blood vessels. Non-specific systemicfeatures such as fever, malaise and weight loss may precede overt jointsymptoms.RA may be associated with other connective tissue diseases and chronicnon inflammatory pain e.g. fibromyalgia. It is also an independent riskfactor for cardiovascular (CV) diseases and osteoporosis.The key presenting symptoms of joint inflammation are: joint pain and swelling early morning stiffness lasting 30 minutesThe typical articular pattern of RA is symmetrical polyarthritis affecting: metacarpophalangeal (MCP) joints proximal interphalangeal (PIP) joints interphalangeal joint of thumbs wrists elbows metatarsophalangeal (MTP) jointsThe symptoms of joint inflammation should be present for at least sixweeks.Findings on physical examination include: clinical synovitis joint tenderness boggy swelling (may be subtle in early RA) restricted range of motion joint deformities e.g. radial deviation of the wrist, ulnar deviationat the MCPs, “swan-neck” [flexion of distal interphalangeal (DIP)joint, hyperextension of PIP] and “boutonniere” (hyperextension ofDIP, flexion of PIP) deformitiesDifferential diagnosis of polyarthritis should take into consideration: duration of symptoms pattern of joint involvement presence of systemic features and/or other diseasesImportant differentials include: psoriatic arthritis erosive inflammatory osteoarthritis polyarticular gout arthritis related to infection systemic lupus erythematosus2

Management of Rheumatoid Arthritis Early diagnosis and prompt treatment of RA are mandatory toprevent irreversible joint damage.Recommendation 1 Consider rheumatoid arthritis if inflammation involving multiple jointsis present for at least six weeks.3

Management of Rheumatoid Arthritis3. INVESTIGATIONSLaboratory and imaging investigations are performed to assist indiagnosis, screen pre-existing abnormalities and co-morbidities, as wellas to monitor treatment-related adverse events (AEs).3.1 Laboratory TestRelevant laboratory tests in RA are shown in table below.Phase ofInvestigationsin RATable 1. Laboratory InvestigationsmanagementDiagnosis Inflammatory markerso Erythrocyte sedimentation rate (ESR) and/oro C-reactive protein (CRP) Rheumatoid factor (RF) and/or Anti-citrullinated peptide antibody (ACPA)*Pre-treatment andco-morbiditiesscreening Treatment:Disease activitymonitoring andtreatment AEs Full blood count (FBC)Renal profile (RP)Fasting blood sugarFasting lipid profileLiver function test (LFT)Viral hepatitis screening [hepatitis B surfaceantigen (HBsAg), hepatitis C antibody] Human immunodeficiency virus (HIV) if risk factorpresentFBCRPLFTESR and CRPPre-biologic therapy Hepatitis B core antibody, if HBsAg negative Mantoux Interferon Gamma Release Assay(IGRA) HIV screening Immunoglobulin (Ig) G, A and M [prior to rituximab(RTX)]*ACPA is interchangeable with anti-cyclic citrullinated peptide (anti-CCP)RF and ACPA have similar diagnostic sensitivity (67% and 79%respectively)1 although ACPA has a higher specificity compared withRF (95 - 98% and 79 - 85% respectively).1-2 Presence of both RF andACPA indicate a more severe disease. ACPA should be considered inclinically suspected RA where RF is negative. Both RF and ACPA arenot recommended for disease monitoring.4

Management of Rheumatoid Arthritis Positive RF does not equate to RA as it is present in normalpopulation with a higher incidence in the elderly.Negative RF does not exclude RA as 30 - 40% of patients with RAare seronegative.3-4Recommendation 2 Inflammatory markers and rheumatoid factor anti-citrullinatedpeptide antibody should be tested when there is clinical suspicion ofrheumatoid arthritis.3.2 Imaging3.2.1 Plain Radiographya. Chest X-RayChest X-ray is performed at baseline evaluation and repeated onfollow-up for assessment of disease complications and co-morbidities.It is also mandatory as part of pre-biologic tuberculosis screening (referto Appendix 8).b. Hand X-RayPlain radiograph is the most common modality used to assessthe joints. It may be normal within the first six months of RA onset.The radiograph findings include soft-tissue swelling, juxta-articulardemineralisation, joint space narrowing and bone erosions. Thesechanges are symmetrical and spare the distal IP joints. Refer toFigure 1 and 2.5

Management ofof RheumatoidRheumatoid ArthritisArthritisManagementABFigureFigure 1.1. AnteroposteriorAnteroposterior viewview (AP)(AP) ofof handshands inin earlyearly RA:RA:(A)(A) periarticularperiarticular osteopeniaosteopenia andand (B)(B) softsoft tissuetissue swellingswellingCAEBDFigureFigure 2.2. APAP andand supinatorsupinator obliqueoblique viewsviews ofof handshands inin advancedadvanced RA:RA:(A)(A) ulnarulnar deviationdeviation ofof fingersfingers atat MCPMCP joints,joints, (B)(B) hitchhiker’shitchhiker’s thumbthumbdeformity,deformity, (C)(C) boutonniereboutonniere deformity,deformity, (D)(D) subchondralsubchondral cyst,cyst, (E)(E) sclerosissclerosisandand jointjoint spacespace narrowingnarrowing atat MCPMCP joints.joints. SimilarSimilar abnormalitiesabnormalities seenseen ininPIP,PIP, radiocarpalradiocarpal andand intercarpalintercarpal joints.joints.3.2.23.2.2 MusculoskeletalMusculoskeletal UltrasoundUltrasoundMusculoskeletalMusculoskeletal ultrasoundultrasound isis aa usefuluseful bedsidebedside tooltool thatthat isis increasinglyincreasinglybeingbeing usedused byby rheumatologistsrheumatologists toto aidaid earlyearly diagnosisdiagnosis andand managementmanagementofof RA.RA. UltrasoundUltrasound isis moremore accurateaccurate thanthan clinicalclinical assessmentassessment inin earlyearly RARApatientspatients especiallyespecially thosethose withwith negativenegative ACPA:ACPA: ClinicalClinical synovitissynovitis (tender(tender oror swollenswollen joint)joint) vsvs subclinicalsubclinical ddetected):(ultrasound detected): GrayGray ScaleScale (GS)(GS) 1: 1: sensitivitysensitivity 58.8%58.8% vsvs 78.0%,78.0%, specificityspecificity79.4%79.4% vsvs 79.4%79.4% GSGS 1/Power 1/Power DopplerDoppler (PD)(PD) 1: 1: sensitivitysensitivity 58.5%58.5% vsvs 56.2%,56.2%,specificity79.4%vs93.7%specificity 79.4% vs 93.7%66

Management of Rheumatoid Arthritis In patients with negative ACPA, combining ultrasound detectedsynovitis joint counts with 2010 ACR/EULAR classificationcriteria increased diagnostic sensitivity from 55.2% to 72.4% andspecificity from 78.5% to 87.7%.6, level II-2Presence of ultrasound detected synovitis increases the prevalenceof clinical synovitis. This may classify patients with musculoskeletalsymptoms more accurately.5-7, level II-2 Ultrasound of the joints is useful in detecting subclinical synovitis forsuspected inflammatory arthritis including RA.3.2.3 Magnetic Resonance ImagingMagnetic resonance imaging (MRI) is another imaging modality todetect synovitis in hands and wrists in early RA which may not beclinically evident: In a systematic review, MRI hand and wrist had good accuracy inthe diagnosis of RA in patients with 6 months disease duration(AUC 0.81).8, level l MRI synovitis in PIP joint is a strong predictor of early RA withouttypical symptoms (OR 3.1, 95% CI 1.2 to 8.1).9, level II-2MRI can detect synovitis, bone erosions and bone marrow oedemabetter than conventional radiography but its use is limited due to costand availability.7

Management of Rheumatoid Arthritis4. CLASSIFICATION CRITERIARA should be suspected in patients who present with inflammatorypolyarthritis. Initial evaluation of such patients requires a careful history,physical examination and selected laboratory tests to identify featuresthat are characteristic of RA. Patients are classified as having RA basedon the criteria established by American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 (refer toTable 2). This classification criteria supersedes the older ACR 1987revised criteria.Table 2. The 2010 American College of Rheumatology/EuropeanLeague Against Rheumatism Classification Criteriafor Rheumatoid ArthritisScoresTarget population (Who should be tested?): Patients who1) have at least 1 joint with definite clinical synovitis (swelling)*2) with the synovitis not better explained by another diseaseClassification criteria for RA (score-based algorithm: add score ofcategories A - D; a score of 6/10 is needed for classification of apatient as having definite RA)A. Joint involvement1 large joint2 - 10 large joints1 - 3 small joints (with or without involvement of large joints)4 - 10 small joints (with or without involvement of large joints) 10 joints (at least 1 small joint)01235B. Serology (at least 1 test result is needed forclassification)Negative RF and negative ACPALow-positive RF or low-positive ACPAHigh-positive RF or high-positive ACPA023C. Acute-phase reactants (at least 1 test result is needed forclassification)Normal CRP and normal ESRAbnormal CRP or abnormal ESR01D. Duration of symptoms 6 weeks 6 weeks01Source: Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritisclassification criteria: an American College of Rheumatology/EuropeanLeague Against Rheumatism collaborative initiative. Arthritis Rheum.2010 Sep;62(9):2569-81.8

Management of Rheumatoid ArthritisA score of 6 is classified as having definite RAA score of 6 may fulfil the criteria over timeThere are four domains in the classification criteria:A. Joint involvement (swollen or tender joint on examination, whichmay be confirmed by imaging evidence of synovitis)Large joints refer to shoulders, elbows, hips, knees and ankles.Small joints refer to MCPs, PIPs, second through fifth MTPs,thumb IPs and wrists.*DIP joints, first carpometacarpal joints and first MTP joints areexcluded from assessment.B. SerologyHigh positive refers to International Unit values 3 times upperlimit normal.C. Acute-phase reactantsNormal or abnormal is determined by local laboratory standards.D. DurationPatient self-report on the duration of signs or symptoms ofsynovitis.5. PROGNOSTIC FACTORSRA outcome is influenced by many factors and awareness of thesefactors can guide the healthcare providers on early referral for initiationof treatment.Poor prognostic factors in RA are: older age (OR 1.45, 95% CI 1.08 to 1.94)10, level II-2 female (OR 3.36, 95% CI 1.20 to 9.40)11, level II-2 obesity (OR 5.2, 95% CI 1.8 to 15.2)12, level I smoking (OR 2.17, 95% CI 1.06 to 4.45)13, level I presence of ACPA/anti-CCP (OR ranging from 1.01 to 4.22)11, level II-2; 14, level I; 15-16, level II-2; 17, level IIIpresence of RF (OR ranging from 2.483 to 3.64)10-11, level II-2; 18, level IIIhigh CRP (OR ranging from 1.04 to 1.52)13, level I; 19, level II-2high ESR (OR ranging from 1.72 to 3.20)11, level II-2; 13, level I; 15, level II-2anaemia20, level II-2high erosion score at baseline (OR ranging from 2.29 to 18.060)13, level I; 16, level II-2; 19, level II-29

Management of Rheumatoid Arthritis6. REFERRALAll RA patients should be primarily managed by rheumatologists. Thisis due to the complexity of making a definite diagnosis and ensuringadequate treatment of the disease.Indications for referral are as listed below:21-22a. Referral for diagnosis1. Clinical suspicion of RA supported by the presence of any of thefollowing: more than three swollen joints MCP/MTP joint involvement with positive squeeze test (referto Figure 3) early morning stiffness of more than 30 minutes2. Clinical evidence of persistent synovitis of undetermined causeFigure 3. Positive Squeeze Testb. Referral following diagnosis1. Development of a co-management plan2. Optimisation of therapy in active disease3. Disease-related complication

Dr. Norhaslira Abdul Rahim Family Medicine Specialist Klinik Kesihatan Sg. Besi, Kuala Lumpur Dr. Shereen Ch'ng Suyin Consultant Rheumatologist Hospital Selayang, Selangor Dr. Tan Bee Eng Consultant Rheumatologist Gleneagles Penang, Pulau Pinang Dr. Zil Azwan Abdullah Family Medicine Specialist Klinik Kesihatan Presint 9, Putrajaya