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
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 Arthritis
Arthritis 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)
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–
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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:
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–
–
–
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•
•
•
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
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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 and
Premature Mortality
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•
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Cardiovascular Disease
Infections
Lymphoproliferative disorders
Gastrointestinal
Interstitial Lung Disease
CARDIOVASCULAR DISEASE IN RA
EPIDEMIOLOGY
• 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
increase risk
2-fold
• RA
increase risk
2.2-fold
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
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↑ CRP (1)
• ↓ Endothelial cell
↑ESR (2)
progenitors (5)
↑IL-6 (3)
• ↑Ox-LDL-ab (6)
↑TNF α (3)
• ↑Proinflammatory
↑Von Willebrand
high-density
factor, Plasminogen lipoprotein. (7)
DH, et al, Arthritis Rheum.
activator inhibitor- (1)Solomon
2004;50(11):3444.
(2)Maradit-Kremers H, et al, Arthritis Rheum.
2005;52(3):722.
1, Fibrinogen (4)
(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
˃naproxen
Naproxen and Ibuprofen attenuate the antiplatelet
effect of aspirin
Traditional Risk Factors for
CAD
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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
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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
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Prevent Joint damage and disability
Prevent Comorbidities
Prevent premature death.
Improve quality of life
Relief symptoms
Achieve clinical REMISSION
Treatment: The Earlier the Better
Sharp
Score
10
9
8
7
6
Early (15 days)
Delayed (123 days)
5
4
3
2
1
0
6 Months 12 Months 18 Months 24 Months
Patients were treated with chloroquine or azathioprine
Lard 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 OPTIONS
DMARDs Agents
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Prednisone
Methotrexate
Hydroxychloroquine
Sufasalazine
Leflunomide
Cyclosporine
Azathioprine
BIOLOGIC Agents
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Etanercept (ENBREL)
Infliximab (REMICADE)
Adalimumab (HUMIRA)
Golimumab (SIMPONI)
Certolizumab (CIMZIA)
Anakinra (KINERET)
Abatacept (ORENCIA)
Rituximab (RITUXAN)
Tocilizumab (ACTEMRA)
Tofacitinib (XELJANZ)
Several Treatment Options
Where 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
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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 TNFI 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; October1721,2009;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