Rheumatoid Arthritis (1 of 23) 1 Patient presents w/ signs & symptoms of rheumatoid arthritis (RA) 2 4 DIAGNOSIS No Is RA confi rmed? ALTERNATIVE DIAGNOSIS Yes A Pharmacological therapy • Conventional synthetic disease-modifying anti-rheumatic drug (DMARD) (csDMARD) monotherapy [Methotrexate (preferred), Lefl unomide or Sulfasalazine] • Adjunctive therapy [corticosteroids, nonsteroidal anti-infl ammatory drugs (NSAIDs)] B Non-pharmacological therapy 3 CONTINUE TREATMENT Symptoms improved Yes • at 3 mth & treatment goal Consider decreasing achieved at 6 mth? dose if in sustained remission No A Pharmacological therapy A Add any one of the Pharmacological following: therapy 3 • TNF inhibitor1 or • Change to or add a No Yes • Non-TNF second csDMARD Are poor prognostic factors 1 B present? biological or Non-pharmacological • Jak-inhibitor therapy MIMS B Non- pharmacological therapy TREATMENT © See next page 1In patients who cannot use csDMARDs as comedication, interleukin-6 receptor antagonists & targeted synthetic DMARDs (tsDMARDs) have some advantages over other biological DMARDs (bDMARDs) Not all products are available or approved for above use in all countries. Specifi c prescribing information may be found in the latest MIMS. B105 © MIMS 2020 Rheumatoid Arthritis (2 of 23) TREATMENT OF PATIENTS W/ POOR PROGNOSTIC FACTORS CONT’D CONTINUE 3 TREATMENT RHEUMATOID ARTHRITIS RHEUMATOID Symptoms improved • Yes Consider decreasing at 3 mth & treatment goal dose or increasing achieved at 6 mth? interval if in sustained remission No A Pharmacological therapy • Switch to another TNF inhibitor or non-TNF biological1 or • Jak-inhibitor B Non-pharmacological therapy 3 Symptoms improved Yes at 3 mth & treatment goal achieved at 6 mth? No 1In patients who failed one TNF inhibitor therapy, considerMIMS giving a second TNF inhibitor or changing to an agent from a diff erent class © Not all products are available or approved for above use in all countries. Specifi c prescribing information may be found in the latest MIMS. B106 © MIMS 2020 Rheumatoid Arthritis (3 of 23) 1 RHEUMATOID ARTHRITIS (RA) • A chronic, infl ammatory arthritis of unknown etiology - Most common autoimmune infl ammatory arthritis in adults - Persistent synovitis leads to joint destruction & deformity Etiology • Smoking increases incidence for developing RA in anti-citrullinated protein antibody (ACPA)-positive patients • Bacteria (eg Escherichia coli, Helicobacter pylori, Mycobacteria, Mycoplasma, Streptococcus), viruses (eg Epstein-Barr virus, rubella, parvovirus) & periodontal disease (Porphyromonas gingivalis) is strongly associated RHEUMATOID ARTHRITIS RHEUMATOID w/ the occurrence of RA Clinical Manifestations General • Joint pain &/or swelling • Morning stiff ness lasting ≥1 hour • Myalgia, fatigue, weight loss, low-grade fever, depression • Typically involves the joints of the fi ngers, wrists, toes - Upper & lower extremity joints are also aff ected (eg shoulders, elbows, knees & ankles) • Syndrome of polymyalgia rheumatica may occasionally be present Early Rheumatoid Arthritis • Duration of occurrence of RA signs & symptoms is <6 months & meets the classifi cation criteria for RA Established Rheumatoid Arthritis • Duration of occurrence of RA signs & symptoms is ≥6 months & meets the classifi cation criteria for RA Palindromic Rheumatism • Follows an episodic pattern - Joints may be aff ected for hours to days followed by symptom-free periods lasting for days to months Undiff erentiated Arthritis • May indicate onset of a polyarticular disease - Interval between monoarthritis & polyarthritis may extend from days to week in patients w/ progressive disease • Large joints are frequently aff ected (eg shoulder, wrist, hip, knee, ankles) • History of joint trauma may be the initiating event Extra-articular Involvement • Anemia, fatigue, pleuropericarditis, interstitial lung disease, neuropathy, scleritis, Sjogren’s syndrome, vasculitis • Subcutaneous rheumatoid nodules on extensor surfaces of elbows & over Achilles tendons • Splenomegaly Physical Findings • Joint pain & swelling are the key features of RA • Limited or restricted range of motion • Hand & foot involvements are common in the early course of RA - Symmetric polyarthritis involving the interphalangeal thumb joints, metacarpophalangeal (MCP) &/or proximal interphalangeal (PIP) joints of the hands & the metatarsophalangeal (MTP) joints of the feet strongly suggests RA • Deformities due to joint & tendon destruction are late manifestations of RA - Ulnar deviation or drift - Radial deviation of wrist - Boutonnière & swan-neck deformities - Hammer toes MIMS - Joint ankylosis (uncommon) - Genu varus or valgus may also be seen secondary to erosion of femoral condyles & tibial plateau Severity of Disease • RA can be characterized as mild, moderate or severe which is best applied to untreated patients Mild Disease • Patients meet the criteria for RA, have <6 infl amed joints, w/ absence of extra-articular involvement & evidence of bone erosions or cartilage loss on X-ray Moderate Disease • Patients have 6-10 infl amed joints • Presence of some of the following: Elevated erythrocyte sedimentation rate (ESR) &/or C-reactive protein (CRP), positive© rheumatoid factor (RF) &/or ACPA, appearance of infl ammation as well as minimal joint space narrowing & small peripheral erosions on X-ray, absence of extra-articular disease Severe Disease • Patients have >20 infl amed joints, elevated ESR &/or CRP • Presence of ≥1 of the following clinical features: Anemia of chronic disease &/or hypoalbuminemia, positive RF &/or ACPA, appearance of bone erosions & cartilage loss on X-ray, presence of extra-articular disease B107 © MIMS 2020 Rheumatoid Arthritis (4 of 23) 2 DIAGNOSIS • Based on clinical signs & symptoms, lab results & imaging features • Early diagnosis is essential in disease impact reduction on diff erent systems New Classifi cation Criteria for Rheumatoid Arthritis • Developed by the American College of Rheumatology (ACR) Board of Directors & European League Against Rheumatism (EULAR) Executive Committee • Can be applied to patients at more than one point in the evolution of their signs & symptoms • RHEUMATOID ARTHRITIS RHEUMATOID Limited only to patients w/ clinical synovitis in at least 1 joint & synovitis not secondary to other disease • A total score of ≥6/10 is needed to classify a patient as having defi nite RA • Number & site of involved joints - 5 points for >10 joints, including at least 1 small joint1 - 3 points for 4-10 small joints1 - 2 points for 1-3 small joints1 - 1 point for 2-10 large joints (eg shoulders, elbows, hips, knees, ankles) • Serological abnormality (at least 1 test result is needed) - 3 points for high-positive [>3x upper limit of normal (ULN)] RF or ACPA - 2 points for low-positive (≤3x ULN) RF or ACPA • Acute-phase reactants abnormality (at least 1 test result is needed) - 1 point for abnormal CRP or ESR • Symptom duration - 1 point for ≥6 weeks Lab Exams Rheumatoid Factor (RF) • Present in approximately 60-80% of patients w/ RA • Not recommended in monitoring patients w/ RA but useful in diagnosis especially if measured w/ ACPA - Presence of both RF & ACPA show a more severe disease • RF titers rarely change w/ disease activity Anti-citrullinated Protein Antibody (ACPA) • Shows similar diagnostic sensitivity as RF but w/ higher specifi city rate of approximately 95-98% • Not recommended in monitoring patients w/ RA Acute Phase Reactants • Infl ammatory markers ESR & CRP are not specifi c for RA but refl ect the degree of synovial infl ammation • Monitoring of these acute phase reactants can be used to assess disease activity Complete Blood Count (CBC) • May show anemia of chronic disease, leukocytosis & thrombocytosis Imaging Studies X-ray • Commonly used to assess the presence of joint damage secondary to RA • Early changes include soft-tissue swelling & juxta-articular demineralization • Later changes involve erosions through the cortex of the bone & around the margins of the joint • Decreased sensitivity if taken during the 1st 6 months of the course of the disease Magnetic Resonance Imaging (MRI) • More sensitive than standard radiographyMIMS for detecting bone destruction • Detects bone erosions & subclinical synovitis earlier in the course of the disease • May be used in patients w/ suggestive cervical myelopathy Ultrasonography • Alternative method to estimate the degree of infl ammation & volume of infl amed tissue • As w/ MRI, shows features of joint infl ammation that are not physically evident (eg subclinical synovitis for suspected RA) & detects bone erosions in early disease • May also be used to assess joints for intra-articular steroid injections • Should not be used for routine disease activity monitoring in adults w/ RA 1Eg MCP joints,© PIP joints, 2nd-5th MTP joints, thumb interphalangeal joint, wrists B108 © MIMS 2020 Rheumatoid Arthritis (5 of 23) 3 ASSESSMENT OF DISEASE ACTIVITY • Several indices are developed to assess disease activity which are useful in monitoring the response to therapy & in defi ning remission • Preferred RA disease activity measurements by ACR for regular clinical use include the Disease Activity Score in 28 Joints (DAS28) w/ ESR or CRP Level, Simplifi ed Disease Activity Index (SDAI), Clinical Disease Activity Index, Patient Activity Scale-II & Routine Assessment of Patient Index Data 3 • Scores are categorized to low, moderate & high disease activity Disease Activity Score 28 (DAS28) RHEUMATOID ARTHRITIS RHEUMATOID • Assesses the patient’s RA disease by measuring the following: