Rheumatoid Arthritis What is Rheumatoid arthritis Pathophysiology What
![Rheumatoid Arthritis: What is Rheumatoid arthritis ? Pathophysiology Rheumatoid Arthritis: What is Rheumatoid arthritis ? Pathophysiology](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-1.jpg)
![What are the clinical features 1. Articular manifestations 2. Articular presentations 3. Extra articular What are the clinical features 1. Articular manifestations 2. Articular presentations 3. Extra articular](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-2.jpg)
![5. Classiifcation criteria • Old and new 6. Juvenile Rheumatoid arthritis 7. Stills disease 5. Classiifcation criteria • Old and new 6. Juvenile Rheumatoid arthritis 7. Stills disease](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-3.jpg)
![• Radiological changes • Treatment : NSAIDS, DMARDs • Treatment Immunosuppression and other • Radiological changes • Treatment : NSAIDS, DMARDs • Treatment Immunosuppression and other](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-4.jpg)
![Boutenniere Boutenniere](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-5.jpg)
![Atlanto axial subluxation Atlanto axial subluxation](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-6.jpg)
![Nodule Nodule](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-7.jpg)
![Caplan syndrome Caplan syndrome](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-8.jpg)
![ILD ILD](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-9.jpg)
![Pleural effusion Pleural effusion](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-10.jpg)
![Out come • Goal of thearpy Out come • Goal of thearpy](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-11.jpg)
![Pathogenesis • Exact mechanism unknown • Most likely related to acute and chronic inflammation Pathogenesis • Exact mechanism unknown • Most likely related to acute and chronic inflammation](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-12.jpg)
![Early RA Early RA](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-13.jpg)
![Rheumatoid arthritis Rheumatoid arthritis](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-14.jpg)
![](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-15.jpg)
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![Treatment Options • Methotrexate has been one of the mainstays of RA treatment – Treatment Options • Methotrexate has been one of the mainstays of RA treatment –](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-17.jpg)
![Etanercept • Recombinant fusion protein of the TNF (tumor necrosis factor) receptor that is Etanercept • Recombinant fusion protein of the TNF (tumor necrosis factor) receptor that is](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-18.jpg)
![Mechanism of Etanercept PC RF Autoantibodies B B Activates T T PC T T Mechanism of Etanercept PC RF Autoantibodies B B Activates T T PC T T](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-19.jpg)
![Clinical Question • Is Etanercept superior to MTX when used as a monotherapy for Clinical Question • Is Etanercept superior to MTX when used as a monotherapy for](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-20.jpg)
![ACR Response Criteria ≥ 20% / 50% / 70% Improvement in: • Number of ACR Response Criteria ≥ 20% / 50% / 70% Improvement in: • Number of](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-21.jpg)
![ERA (Early rheumatoid arthritis trial) ERA (Early rheumatoid arthritis trial)](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-22.jpg)
![Tempo Trial MTX Klareskog et al. Lancet. 2004; 363: 675 Tempo Trial MTX Klareskog et al. Lancet. 2004; 363: 675](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-23.jpg)
![COMET – combo vs monotherapy 86 71 67 49 48 28 Emery et al. COMET – combo vs monotherapy 86 71 67 49 48 28 Emery et al.](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-24.jpg)
![Negatives / Side effects • Entanercept – Injection site infections – Good safety profile Negatives / Side effects • Entanercept – Injection site infections – Good safety profile](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-25.jpg)
![Conclusions • Patients on Etanercept vs MTX monotherapy experience a small but statistically significant Conclusions • Patients on Etanercept vs MTX monotherapy experience a small but statistically significant](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-26.jpg)
- Slides: 26
![Rheumatoid Arthritis What is Rheumatoid arthritis Pathophysiology Rheumatoid Arthritis: What is Rheumatoid arthritis ? Pathophysiology](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-1.jpg)
Rheumatoid Arthritis: What is Rheumatoid arthritis ? Pathophysiology
![What are the clinical features 1 Articular manifestations 2 Articular presentations 3 Extra articular What are the clinical features 1. Articular manifestations 2. Articular presentations 3. Extra articular](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-2.jpg)
What are the clinical features 1. Articular manifestations 2. Articular presentations 3. Extra articular manifestations? Eyes, Hemtological, systemic symptoms, RS, CVS, CNS, Abdomen , 4. general symptoms and skin examination findings 5. Joint deformities
![5 Classiifcation criteria Old and new 6 Juvenile Rheumatoid arthritis 7 Stills disease 5. Classiifcation criteria • Old and new 6. Juvenile Rheumatoid arthritis 7. Stills disease](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-3.jpg)
5. Classiifcation criteria • Old and new 6. Juvenile Rheumatoid arthritis 7. Stills disease 8. Felty`s Syndrome 9. Investigations 10 Assessment of severity
![Radiological changes Treatment NSAIDS DMARDs Treatment Immunosuppression and other • Radiological changes • Treatment : NSAIDS, DMARDs • Treatment Immunosuppression and other](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-4.jpg)
• Radiological changes • Treatment : NSAIDS, DMARDs • Treatment Immunosuppression and other agents • Treatment-Biological response modifiers • Physiotherapy • Surgeons role
![Boutenniere Boutenniere](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-5.jpg)
Boutenniere
![Atlanto axial subluxation Atlanto axial subluxation](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-6.jpg)
Atlanto axial subluxation
![Nodule Nodule](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-7.jpg)
Nodule
![Caplan syndrome Caplan syndrome](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-8.jpg)
Caplan syndrome
![ILD ILD](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-9.jpg)
ILD
![Pleural effusion Pleural effusion](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-10.jpg)
Pleural effusion
![Out come Goal of thearpy Out come • Goal of thearpy](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-11.jpg)
Out come • Goal of thearpy
![Pathogenesis Exact mechanism unknown Most likely related to acute and chronic inflammation Pathogenesis • Exact mechanism unknown • Most likely related to acute and chronic inflammation](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-12.jpg)
Pathogenesis • Exact mechanism unknown • Most likely related to acute and chronic inflammation in the synovium in addition to a proliferate and destructive process of joint tissues
![Early RA Early RA](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-13.jpg)
Early RA
![Rheumatoid arthritis Rheumatoid arthritis](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-14.jpg)
Rheumatoid arthritis
![](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-15.jpg)
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![Treatment Options Methotrexate has been one of the mainstays of RA treatment Treatment Options • Methotrexate has been one of the mainstays of RA treatment –](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-17.jpg)
Treatment Options • Methotrexate has been one of the mainstays of RA treatment – Action: Inhibits dihydrofolate reductase • Over the past few years newer biologic disease modifying anti-rheumatic drugs have been developed • These drugs target select aspects of the immune response so as to decrease inflammation
![Etanercept Recombinant fusion protein of the TNF tumor necrosis factor receptor that is Etanercept • Recombinant fusion protein of the TNF (tumor necrosis factor) receptor that is](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-18.jpg)
Etanercept • Recombinant fusion protein of the TNF (tumor necrosis factor) receptor that is solubilized by linking to the Fc portion of human Ig. G 1 • Inhibits TNF : cytokine produced primarily by macrophages • Administered by subcutaneous injection twice weekly • Extremely expensive
![Mechanism of Etanercept PC RF Autoantibodies B B Activates T T PC T T Mechanism of Etanercept PC RF Autoantibodies B B Activates T T PC T T](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-19.jpg)
Mechanism of Etanercept PC RF Autoantibodies B B Activates T T PC T T APC/DC T T Inflammation Joint damage FLS Activates FLS X Etanercept TNFa MΦ MΦ
![Clinical Question Is Etanercept superior to MTX when used as a monotherapy for Clinical Question • Is Etanercept superior to MTX when used as a monotherapy for](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-20.jpg)
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?
![ACR Response Criteria 20 50 70 Improvement in Number of ACR Response Criteria ≥ 20% / 50% / 70% Improvement in: • Number of](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-21.jpg)
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
![ERA Early rheumatoid arthritis trial ERA (Early rheumatoid arthritis trial)](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-22.jpg)
ERA (Early rheumatoid arthritis trial)
![Tempo Trial MTX Klareskog et al Lancet 2004 363 675 Tempo Trial MTX Klareskog et al. Lancet. 2004; 363: 675](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-23.jpg)
Tempo Trial MTX Klareskog et al. Lancet. 2004; 363: 675
![COMET combo vs monotherapy 86 71 67 49 48 28 Emery et al COMET – combo vs monotherapy 86 71 67 49 48 28 Emery et al.](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-24.jpg)
COMET – combo vs monotherapy 86 71 67 49 48 28 Emery et al. Lancet 2008; 372: 375– 82
![Negatives Side effects Entanercept Injection site infections Good safety profile Negatives / Side effects • Entanercept – Injection site infections – Good safety profile](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-25.jpg)
Negatives / Side effects • Entanercept – Injection site infections – Good safety profile for the most part – rare events resulting from immunosuppression (TB, opportunistic infections, URIs), slightly increased risk of lymphoma and CHF, drug induced lupus • MTX – Pneumonitis, hepatic toxicity, anemia, thrombocytopenia, leukopenia, slightly increased risk of lymphoma, alopecia, mouth ulcers, N/V - Frequent laboratory testing needed. (3 -6 times a year) Requires folic acid supplementation.
![Conclusions Patients on Etanercept vs MTX monotherapy experience a small but statistically significant Conclusions • Patients on Etanercept vs MTX monotherapy experience a small but statistically significant](https://slidetodoc.com/presentation_image_h/28882160b11b49751875099d4ccdf9e2/image-26.jpg)
Conclusions • Patients on Etanercept vs MTX monotherapy experience a small but statistically significant improvement in ACR 20, 50, 70 at 1 year. Etanercept reduced disease activity, arrested structural damage, and decreased disability more effectively then MTX. • Etanercept has been shown to be a safe therapy which actually has a slightly lower serious infection rate then MTX. • Combination therapy is substantially more effective in achieving all ACR levels then eitherapy alone and should be used without hesitation in severe cases of RA. • Combination therapy results in no increase in serious infection rates over MTX alone.
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