rheumatoid arthritis update
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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. - PowerPoint PPT PresentationTRANSCRIPT
Rheumatoid Arthritis Update
Ivonne Herrera, MDRheumatologist
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 Renoir1841-1919
Rheumatoid Arthritis• Disabling• Destructive• Cause of mortality as well as
morbidity
Rheumatoid Arthritis • RA is a symmetric,
peripheral polyarthritis of unknown etiology.
• If untreated, leads to joint deformity and destruction.
Rheumatoid ArthritisArthritis that affects the MCP and/or PIP joints of both hands,
strongly suggests RA
Rheumatoid Arthritis
Early Intermediate Late
Changes in the joint
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
Other Laboratory Features• Elevated acute phase reactants:
– ESR – CRP– Leukocytosis – Thrombocytosis
• Anemia of chronic disease• Hypoalbuminemia• ANA +• Inflammatory Synovial Fluid: White cells
>2000
Imaging Studies
• Plain film radiography
• Color Doppler Ultrasonography
• MRI
Plain Film Radiography in RA• Soft tissue swelling
• Peri-articular osteopenia
• Decrease joint space
• Bony erosions
Plain Film Radiography in RA
MCP and PIP erosions:
– 1st year: • 15-30% of patients
– 2nd year: • 90% of patients
Atlantoaxial Subluxation in RA
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
Ultrasonography AAAAA
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
2010 ACR/EULAR Criteria
Differential Diagnosis• Acute viral
polyarthritis:– Parvovirus B 19– Hepatitis B or C– HTLV-1
• CTD: SLE, Sjogren’s, etc– Overlap syndrome– Jaccoud’s
arthropathy
• Psoriatic arthritis• Gout and
Pseudogout• Myelodysplasia• Erosive OA• PMR• Sarcoidosis
RA: Morbidity andPremature Mortality
• Cardiovascular Disease• Infections• Lymphoproliferative disorders• Gastrointestinal• Interstitial Lung Disease
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)
(1)Aviña-Zubieta JA, et al, Arthritis Rheum. 2008;59(12):1690.
(2) Maradit-Kremers H, et al, Arthritis Rheum. 2005;52(2):402.
RISK OF CVD
• DM type II 2-fold increase risk
• RA 2.2-fold increase risk
The increase incidence of cardiovascular events in RA
patients can not be completely explained by traditional
cardiovascular risk factors
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
Biomarkers for atherosclerosis in patients with RA
• ↑ CRP (1)• ↑ESR (2)• ↑IL-6 (3)• ↑TNF α (3)• ↑Von Willebrand
factor, Plasminogen activator inhibitor-1, Fibrinogen (4)
• ↓ Endothelial cell progenitors (5)
• ↑Ox-LDL-ab (6)• ↑Proinflammatory
high-density lipoprotein. (7)
(1)Solomon DH, et al, Arthritis Rheum. 2004;50(11):3444.
(2)Maradit-Kremers H, et al, Arthritis Rheum. 2005;52(3):722.
(3)Rho YH, et al, Arthritis Rheum. 2009;61(11):1580 (4)Wållberg-Jonsson S, et al, J Rheumatol.
2000;27(1):71. (5)Grisar J,et al, Circulation. 2005;111(2):204.(6)Peters MJ, J Rheumatol. 2008;35(8):1495.(7)Charles-Schoeman et al, Arthritis Rheum.
2009;60(10):2870
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 ˃naproxenNaproxen and Ibuprofen attenuate the antiplatelet effect of aspirin
Traditional Risk Factors for CAD• Hypertention • Smoking• Dyslipidemia • Obesity • Diabetes• Age• Sedentary lifestyle• Family history CAD
• Rheumatoid Arthritis..!
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)
(1)Chung CP, et al, Arthritis Rheum. 2005;52(10):3045
(2)Roman MJ, et al, Ann Intern Med. 2006;144(4):249.
(3)Kao AH, et all, J Rheumatol. 2008;35(1):61.
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)
(1)Maradit-Kremers H, et all, Arthritis Rheum. 2005;52(2):402(2)Douglas KM, et all, Ann Rheum Dis. 2006;65(3):348.
Prevention of CHD in RA patients
• Smoking cessation• Dyslipidemia control• Healthy diet• Exercise• Weight control• Blood pressure control
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) Jacobsson LT, et al, J Rheumatol. 2005;32(7):1213
Early and aggressive therapy in patients with Rheumatoid Arthritis
Prevent severe joint destruction and deformities
Reduce the risk of CVD and CAD
Treatment Goal in RA• Prevent Joint damage and disability • Prevent Comorbidities• Prevent premature death.• Improve quality of life• Relief symptoms• Achieve clinical REMISSION
Treatment: The Earlier the BetterSharp Score
6 Months 12 Months 18 Months 24 Months0123456789
10
Early (15 days)Delayed (123 days)
Patients were treated with chloroquine or azathioprineLard LR, et al. Am J Med. 2001;111:446-451.
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 der Heijde DM. J Rheum. 1995:34 (suppl 2):74-78.
RA: TREATMENT OPTIONSDMARDs Agents• Prednisone• Methotrexate• Hydroxychloroquine• Sufasalazine• Leflunomide• Cyclosporine• Azathioprine
BIOLOGIC Agents• Etanercept (ENBREL)• Infliximab (REMICADE)• Adalimumab (HUMIRA)• Golimumab (SIMPONI)• Certolizumab (CIMZIA)• Anakinra (KINERET)• Abatacept (ORENCIA)• Rituximab (RITUXAN)• Tocilizumab (ACTEMRA)• Tofacitinib (XELJANZ)
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
Efficacy of Biologic Agents• Efficacy often superior to DMARDs• Rapid onset of action• Well tolerated• Sustained response in many
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 radiographically than 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
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.
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
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
QUESTIONS
Thank you