Rheumatoid Arthritis What is Rheumatoid arthritis Pathophysiology What

Rheumatoid Arthritis: What is Rheumatoid arthritis ? Pathophysiology

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 8. Felty`s Syndrome 9. Investigations 10 Assessment of severity

• Radiological changes • Treatment : NSAIDS, DMARDs • Treatment Immunosuppression and other agents • Treatment-Biological response modifiers • Physiotherapy • Surgeons role

Boutenniere

Atlanto axial subluxation

Nodule

Caplan syndrome

ILD

Pleural effusion

Out come • Goal of thearpy

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

Rheumatoid arthritis

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 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 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 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 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)

Tempo Trial MTX Klareskog et al. Lancet. 2004; 363: 675

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 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 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.