rheumatoid arthritis proj

8/12/2019 Rheumatoid Arthritis Proj

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Efficacy of Methotrexate and/or

Etanercept for treatment of RA

Rheumatoid Arthritis:


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Rheumatoid Arthritis

RA has an incredibly high disease burdenand cost to society

Drastic affect on quality of life

Increased disability (80% disabled after 20years of disease)

Patients with RA have shorter life

expectancies It is important to initiate therapy early so

as to halt/slow disease progression


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Pathogenesis

Exact mechanism unknown

Most likely related to acute and chronicinflammation in the synovium in addition to

a proliferate and destructive process of

joint tissues


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Treatment Options

Methotrexate has been one of themainstays of RA treatment

Action: Inhibits dihydrofolate reductase

Over the past few years newer biologicdisease modifying anti-rheumatic drugshave been developed

These drugs target select aspects of theimmune response so as to decreaseinflammation


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Etanercept

Recombinant fusion protein of the TNF (tumornecrosis factor) receptor that is solubilized bylinking to the Fc portion of human IgG1

Inhibits TNF: cytokine produced primarily bymacrophages

Administered by subcutaneous injection twice

weekly

Extremely expensive


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TNF

RF

Autoantibodies

Activates

ActivatesActivates

Inflammation

Joint damage

BB

T

T T

T

FLS

PC

PC

FLS

M M

T T

APC/DC

Mechanism of Etanercept

EtanerceptX


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Clinical Question

Is Etanercept superior to MTX when used

as a monotherapy for early RA?

Is combination therapy consisting of both

MTX and Etanercept superior to either

MTX or Etanercept alone?


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ACR Response Criteria

20% / 50% / 70% Improvement in:Number of swollen joints (SJC)

Number of tender joints (TJC)

Improvement of at least three of the following:

Patient Global Assessment

Physician Global Assessment

Patient Pain Scale

Health Assessment Questionnaire (HAQ)ESR or CRP

Felson DT et al. Arthritis Rheum. 1993; 41: 1564-1570


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ERA (Early rheumatoid arthritis trial)


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Tempo Trial

MTX

Klareskog et al. Lancet.2004;363:675


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COMETcombo vs monotherapy

ACR Score

0

20

40

60

80

100

AR20 ACR50 ACR70

Pr

oportionofpatien

ts(%)

Methotrexate

Etanercept +

Methotrexate86

71

48

67

49

28

Emery et al. Lancet 2008; 372: 37582


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Negatives / Side effects

Entanercept Injection site infections

Good safety profile for the most partrare eventsresulting from immunosuppression (TB, opportunistic

infections, URIs), slightly increased risk of lymphomaand CHF, drug induced lupus

MTX

Pneumonitis,hepatic toxicity, anemia,thrombocytopenia, leukopenia, slightly increased riskof lymphoma, alopecia, mouth ulcers, N/V

- Frequent laboratory testing needed. (3-6 times ayear) Requires folic acid supplementation.


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Conclusions Patients on Etanercept vs MTX monotherapy experience

a small but statistically significant improvement in ACR20,50,70 at 1 year. Etanercept reduced disease activity,arrested structural damage, and decreased disabilitymore effectively then MTX.

Etanercept has been shown to be a safe therapy whichactually has a slightly lower serious infection rate thenMTX.

Combination therapy is substantially more effective in

achieving all ACR levels then either therapy alone andshould be used without hesitation in severe cases of RA.

Combination therapy results in no increase in seriousinfection rates over MTX alone.

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