Date post: | 03-Jun-2018 |
Category: |
Documents |
Upload: | iwin-soossay-sathianathan |
View: | 215 times |
Download: | 0 times |
of 15
8/12/2019 Rheumatoid Arthritis Proj
1/15
Efficacy of Methotrexate and/or
Etanercept for treatment of RA
Rheumatoid Arthritis:
8/12/2019 Rheumatoid Arthritis Proj
2/15
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
8/12/2019 Rheumatoid Arthritis Proj
3/15
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
8/12/2019 Rheumatoid Arthritis Proj
4/15
8/12/2019 Rheumatoid Arthritis Proj
5/15
8/12/2019 Rheumatoid Arthritis Proj
6/15
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
8/12/2019 Rheumatoid Arthritis Proj
7/15
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
8/12/2019 Rheumatoid Arthritis Proj
8/15
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
8/12/2019 Rheumatoid Arthritis Proj
9/15
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?
8/12/2019 Rheumatoid Arthritis Proj
10/15
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
8/12/2019 Rheumatoid Arthritis Proj
11/15
ERA (Early rheumatoid arthritis trial)
8/12/2019 Rheumatoid Arthritis Proj
12/15
Tempo Trial
MTX
Klareskog et al. Lancet.2004;363:675
8/12/2019 Rheumatoid Arthritis Proj
13/15
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
8/12/2019 Rheumatoid Arthritis Proj
14/15
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.
8/12/2019 Rheumatoid Arthritis Proj
15/15
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.