Rheumatoid Arthritis Pharmacotherapy Flashcards
Define RA and its pathophysiology
Chronic autoimmune inflammatory condition
- Genetic disposition
- T-cell mediated immune response
- Inflammatory response
- Angiogenesis in synovium
- Synovial cell proliferation
- Pannus Invasion
- Protease, Prostaglandin and Cytokines
- Articular Cartilage and underlying bone destruction
Diagnostic Criteria for RA
At least 4 of the following:
1) Anti-RF autoantibodies / Anti-CCP
2) Early morning stiffness ≥ 1h ≥ 6 wks
3) Swelling of ≥ 3 joints ≥ 6 wks
4) Swelling of wrist/MCP/PIP ≥ 6 wks
5) Rheumatoid nodules
6) Radiographic changes
Subjective Clinical Presentation of RA
Symmetrical Polyarthritis with pain, swelling, red, warm and early morning stiffness > 30 min
- Small Joints
- Large Joints
- Systemic Symptoms (Ache, fatigue, fever, weight loss, depression)
- Extra-articular complications
Deformities (Swan-neck)
Loss of ADL function
Laboratory Findings for RA
- Autoantibodies (RF, CCP)
- ESR and CRP rise (Acute phase response)
- FBC (Hct & Hg drop, WBC & Plt rise)
- Radiologic (Narrow joint space, erosion, hypertrophic synovial tissue)
Goals of RA treatment
Remission or Low disease activity at 6 months
Boolean 2.0 criteria for remission:
- Tender joint count ≤ 1
- Swollen joint count ≤ 1
- CRP ≤ 1 mg/dL
- Patient global assessment (PGA) using 10 cm VAS ≤ 2 cm
Functional improvement and reduce progression
Pain management
Role of NSAIDs in RA
Adjunct to DMARD for pain relief and minor inflammation (Effect in 1-2 weeks)
Role of glucocorticoids in RA
- Low-dose bridging therapy (Oral)
- Control flare (Intraarticular)
What is the approach to pharmacotherapy in RA? What is the dosing for the glucocorticoid used?
1) DMARD Treatment
2) Bridging therapy: PO Prednisolone 7.5mg/day up to 3 months (Tapered and Discontinue if bDMARD or tsDMARD initiation)
How to choose what DMARD to start for RA? Give MTX dosing as well (Initial, increments, target).
High activity:
- MTX 7.5mg QD + Folic acid 5mg/wk
- Increase by 2.5-5 mg/week every 4-12 weeks
- Target dose: 15mg/week within 4-6 weeks of initiation
Low activity:
- Hydroxychloroquine (Tolerability) >
Sulfasalazine (Less immunosuppressive) >
MTX (Dosing flexibility) > Leflunomide
Dosing for sulfasalazine, hydroxychloroquine, leflunomide
Sulfa: 500 mg QD or BD => 1g BD maintenance
Hydroxy: 200-400 mg in 1-2 divided doses (5mg/kg max)
Leflu: 100 mg/day for 3 days LD, 20 mg/day MD
Hepatic and Renal impairment - Which csDMARD cannot use?
MTX: CrCL< 30 mL/min
Leflu: ALT > 2 X ULN
Teratogenic - Which csDMARDs?
MTX and Leflunomide
Contraindications of sulfasalazine and hydroxychloroquine
Sulfasalazine: Sulfonamide allergy, G6PD deficiency
Hydroxychloroquine: Preexisting retinopathy, G6PD deficiency
If patients are on MTX but not at target, what should be done?
1) Adding bDMARD OR tsDMARD to MTX
- Switch bDMARD or tsDMARd if using already
2) Triple Therapy: Add hydroxychloroquine and sulfasalazine (Less ADR, cost)
Contraindications to bDMARD / tsDMARD
- Severe infections (Sepsis, TB, opportunistic)
- Heart failure (TNF-alpha) and Risk of MACE
- Thrombotic risk patients (JAK & IL-6 inhibitor)
- GI perforation (JAK & IL-6 inhibitor)
