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