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Rheumatoid Arthritis Update

Rheumatoid Arthritis Update. Ivonne Herrera, MD Rheumatologist July 20, 2013. Disclosure. Nothing to be disclosed. Outline. Clinical presentation Diagnosis: New diagnostic criteria for RA (2010) Morbidity and Mortality Treatment options. Pierre Auguste Renoir 1841-1919.

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Rheumatoid Arthritis Update

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  1. Rheumatoid Arthritis Update Ivonne Herrera, MD Rheumatologist July 20, 2013

  2. Disclosure • Nothing to be disclosed

  3. Outline • Clinical presentation • Diagnosis: New diagnostic criteria for RA (2010) • Morbidity and Mortality • Treatment options

  4. Pierre Auguste Renoir1841-1919

  5. Rheumatoid Arthritis • Disabling • Destructive • Cause of mortality as well as morbidity

  6. Rheumatoid Arthritis • RA is a symmetric, peripheral polyarthritis of unknown etiology. • If untreated, leads to joint deformity and destruction.

  7. Rheumatoid ArthritisArthritis that affects the MCP and/or PIP joints of both hands, strongly suggests RA

  8. Rheumatoid ArthritisEarly Intermediate Late

  9. Changes in the joint

  10. RA:Laboratory Features • Rheumatoid Factor (RF) • 70-80% RA patients. • Virtually all patients with Mixed Cryoglobulinemia • Sjogren’s Syndrome 70 % • Hepatitis C/B or other chronic infections 50% • SLE 30% • Healthy individuals 5-10% • Anti-CCP: • Similar sensitivity to RF for RA • 95%-98% specificity • Useful to differentiate RA from infections

  11. Other Laboratory Features • Elevated acute phase reactants: • ESR • CRP • Leukocytosis • Thrombocytosis • Anemia of chronic disease • Hypoalbuminemia • ANA + • Inflammatory Synovial Fluid: White cells >2000

  12. Imaging Studies • Plain film radiography • Color Doppler Ultrasonography • MRI

  13. Plain Film Radiography in RA • Soft tissue swelling • Peri-articularosteopenia • Decrease joint space • Bony erosions

  14. Plain Film Radiography in RA MCP and PIP erosions: • 1st year: • 15-30% of patients • 2nd year: • 90% of patients

  15. AtlantoaxialSubluxation in RA

  16. MRI • Allows early detection of: • Synovitis • Bone edema • Erosions • More sensitive and specific than XRays to identify erosions • 4 months: 45% of patients have erosions

  17. Ultrasonography AAAAA

  18. RA Diagnosis: 1987 ACR Criteria • Morning Stiffness: at least 1 hour • Arthritis of 3 or more joints • Arthritis of at least 1 joint in the hand • Symmetric arthritis • Rheumatoid nodules • Serum Rheumatoid Factor (+) • Radiographic changes: erosions RA Diagnosis: 4 out of 7 criteria

  19. 2010 ACR/EULAR Criteria

  20. Differential Diagnosis • Acute viral polyarthritis: • Parvovirus B 19 • Hepatitis B or C • HTLV-1 • CTD: SLE, Sjogren’s, etc • Overlap syndrome • Jaccoud’sarthropathy • Psoriatic arthritis • Gout and Pseudogout • Myelodysplasia • Erosive OA • PMR • Sarcoidosis

  21. RA: Morbidity andPremature Mortality • Cardiovascular Disease • Infections • Lymphoproliferative disorders • Gastrointestinal • Interstitial Lung Disease

  22. CARDIOVASCULAR DISEASE IN RAEPIDEMIOLOGY • RA ↑ risk of premature death. • The risk of CAD mortality was 59 % higher in patients with RA than in the general population (1) • The risk of CAD in RA patients precedes the ACR criteria-based diagnosis of RA (2) Aviña-Zubieta JA, et al, Arthritis Rheum. 2008;59(12):1690. (2) Maradit-Kremers H, et al, Arthritis Rheum. 2005;52(2):402.

  23. RISK OF CVD • DM type II 2-fold increase risk • RA 2.2-fold increase risk

  24. The increase incidence of cardiovascular events in RA patients can not be completely explained by traditional cardiovascular risk factors

  25. CARDIOVASCULAR DISEASE IN RA: PATHOGENESIS • In the general population inflammation has a significant role in the development of CAD • Chronic inflammation in RA may enhance the development of atherosclerosis - Cytokines - Immune complexes - Coagulation abnormalities

  26. Biomarkers for atherosclerosis in patients with RA • ↑ CRP (1) • ↑ESR (2) • ↑IL-6 (3) • ↑TNF α (3) • ↑Von Willebrandfactor, Plasminogen activator inhibitor-1, Fibrinogen (4) • ↓ Endothelial cell progenitors (5) • ↑Ox-LDL-ab (6) • ↑Proinflammatory high-density lipoprotein. (7) Solomon DH, et al, Arthritis Rheum. 2004;50(11):3444. Maradit-KremersH, et al, Arthritis Rheum. 2005;52(3):722. Rho YH, et al, Arthritis Rheum. 2009;61(11):1580 Wållberg-JonssonS, et al, J Rheumatol. 2000;27(1):71. GrisarJ,et al, Circulation. 2005;111(2):204. Peters MJ, J Rheumatol. 2008;35(8):1495. Charles-Schoemanet al, Arthritis Rheum. 2009;60(10):2870

  27. CVD IN RA: PATHOGENESIS • Medications used in RA patients: • Glucocorticoids • Prednisone >7.5mg/day: ↑ MI, CVA, CHF, Mortality • NSAIDs: • Diclofenac • Ibuprofen • Naproxen • COX-2 inhibitors: Celecoxib Risk of MI: ibuprofen ˃Celecoxib ˃diclofenal ˃naproxen Naproxen and Ibuprofen attenuate the antiplatelet effect of aspirin

  28. Traditional Risk Factors for CAD • Hypertention • Smoking • Dyslipidemia • Obesity • Diabetes • Age • Sedentary lifestyle • Family history CAD • Rheumatoid Arthritis..!

  29. RA AS AN INDEPENDENT RISK FACTOR OF CAD • ↑ Prevalence of traditional risk factors (1) • ↑ Prevalence of preclinical atherosclerosis independent of traditional risk factors (2) • Coronary artery calcification on CT scanning is more prevalent in RA patients independent of other CAD risk factors(3) Chung CP, et al, Arthritis Rheum.2005;52(10):3045 Roman MJ, et al, Ann Intern Med. 2006;144(4):249. Kao AH, et all, J Rheumatol. 2008;35(1):61.

  30. Clinical manifestations of CAD in RA patients • ↑ unrecognized MI and sudden cardiac death (1) • Patients with RA are less likely to report chest pain during an acute coronary event (2) Maradit-Kremers H, et all, Arthritis Rheum. 2005;52(2):402 Douglas KM, et all, Ann Rheum Dis. 2006;65(3):348.

  31. Prevention of CHD in RA patients • Smoking cessation • Dyslipidemia control • Healthy diet • Exercise • Weight control • Blood pressure control

  32. Prevention of CHD in RA patients: Early aggressive therapy for RA • MTX is associated with a reduced risk of CVD events in patients with RA (1) • Risk of MI is markedly reduced in those who respond to TNF blockers by 6 months compared with nonresponders (2) • Risk of CVD is lower in patients with RA treated with TNF blockers (3) (1) Westlake SL, et al, Rheumatology (Oxford). 2010;49(2):295. (2) Dixon WG, et al, Arthritis Rheum. 2007;56(9):2905. (3)JacobssonLT, et al, J Rheumatol. 2005;32(7):1213

  33. Early and aggressive therapy in patients with Rheumatoid Arthritis Prevent severe joint destruction and deformities Reduce the risk of CVD and CAD

  34. Treatment Goal in RA • Prevent Joint damage and disability • Prevent Comorbidities • Prevent premature death. • Improve quality of life • Relief symptoms • Achieve clinical REMISSION

  35. Treatment: The Earlier the BetterSharp Score Patients were treated with chloroquine or azathioprine Lard LR, et al. Am J Med. 2001;111:446-451.

  36. Therapeutic Window of Opportunity • Erosive changes occur EARLY in disease • Delay of therapy can have a significant impact • Early DMARD treatment that suppresses the disease appears to reset the rate of progression for years to come O’Dell JR. Arthritis Rheum. 2002;46:283-285. Van derHeijde DM. J Rheum. 1995:34 (suppl 2):74-78.

  37. RA: TREATMENT OPTIONS DMARDs Agents BIOLOGIC Agents Etanercept (ENBREL) Infliximab (REMICADE) Adalimumab (HUMIRA) Golimumab (SIMPONI) Certolizumab (CIMZIA) Anakinra (KINERET) Abatacept (ORENCIA) Rituximab (RITUXAN) Tocilizumab (ACTEMRA) Tofacitinib (XELJANZ) • Prednisone • Methotrexate • Hydroxychloroquine • Sufasalazine • Leflunomide • Cyclosporine • Azathioprine

  38. Several Treatment OptionsWhere should we start? • Methotrexate (MTX) is the most widely used DMARD • SWEFOT *: Monotherapy with MTX • 30% patients responded to initial 3-4months of MTX • 16% in remission • 75% MTX patients maintain low disease activity at 12 months (DAS28<3.2) *Van Vollenhoven RF, et al. Lancet. 2009;374(9688):459-466

  39. Efficacy of Biologic Agents • Efficacy often superior to DMARDs • Rapid onset of action • Well tolerated • Sustained response in many

  40. Evidence Based Medicine with Biologic Agents • The initial use of TNFi or biologic agents with MTX in early RA resulted in significant decreases in radiographic progression in early RA patients (1) • Initial use of TNFi + MTX is more effective clinically than MTX monotherapy in early RA patients (2) • ABA+MTX is more effective clinically and radiographicallythan MTX monotherapy in early RA patients (3) (1)Smolen JS, et al. Lancet. 2007;370(9602):1861-1874) (2)Breedveld FC, et al.Arthritis Rheum.2006;54(1):26-37) (3)Westhovens R, et al.Ann Rheum Dis. 2009;68(12):1870-77

  41. Evidence Based Medicine with Biologic Agents • In patients with early RA who do not achieve LDA with MTX monotherapy, adding a TNFi results in less radiographic progression than adding of non-biologic DMARD(1) • Rituximab is clinically and radiographically effective in TNF-I R patients(2) • Abatacet is clinically effective in TNF-IR patients(3) • Tocilizumab is clinically effective in TNF-IR patients(4) (1)Van Vollenhoven RF, et al. Presented at: 2009 ACR Scientific meeting; October17- 21,2009;Philladelphia, PA. Abstract LB6. (2)Cohen SB, et al. Arthritis Rheum. 2006;54(9):2793-2806. (3)Genovesse MC, et al. Ann Rheum Dis. 2008;67(4):547-554. (4)Emery P, et al. Ann Rheum Dis. 2008;67:1516-1523.

  42. Safety considerations with Biologics • Serious infections • Opportunistic infections (TB) • Malignancies • Demyelination • Hematologic abnormalities • COPD • Administration reactions • CHF • Hepatic impairment • Autoantibodies and Drug induced Lupus • GI perforation • Progressive multifocal leukoencephalopathy

  43. Rheumatoid Arthritis: Summary • Early Diagnosis: Apply the new 2010 Diagnostic criteria for RA • Early aggressive intervention: in patients with RA, critical to best possible outcome • The combination of MTX plus a biologics is frequently more effective than either agent alone • Tight control of traditional risk factors for CAD and early aggressive therapy for RA may reduce the risk of CVD

  44. QUESTIONS Thank you

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