OA RA Flashcards
OA not done
Is RA more common in women or men?
Women
Does RA have genetic predisposition?
Yes.
- Human Lymphocyte Antigen (HLA) typing HLA-DR4 and/or HLA-DR1 in major histocompatibility complex region
- More likely if parents are RF+ve
- Twin (6x more likely if dizygotic; 30x more likely if monozygotic)
- Fam Hx of inflammatory conditions (RA, lupus etc)
Clinical presentation of RA
- Pain
- Swelling (feels soft & “spongy”)
- Erythematous (redness) & warm
- Early morning stiffness > 30 min (duration correlated with disease activity) takes long time for pain, stiffness to go away.
- Symmetrical polyarthritis (may start with unilateral joint at first)
Small joints (commonly starts w MCP & PIP of hand, IP of thumb, wrist & MTP of toes…)
Large joints (elbows, shoulders, hips, knees, ankles…)
Systemic smx of RA
- Generalised aching/stiffness
- Fatigue
- Fever
- Weight loss
- Depression
- Particularly present in those w disease onset > 60y/o, & up to one third of those with acute onset of polyarthritis.
Chronic clinical presentation of RA
Deformities:
- “Swan neck”
- “Boutonnèire”
- Z-shaped thumb
- MCP subluxation
- Ulnar deviation
- Rheumatoid nodules (elbow)
- Popliteal cyst (knee)
- MTP subluxation (toes)
Loss of physical function & ability to carry out ADL
What labs suggests RA?
Autoantibodies:
- Rheumatoid factor, RF (+ve)
- Anti citrullinated peptide antibodies, ACPA, using anti-CCP assays (+ve)
- Doesnt mean -ve means no RA, sometimes early disease states, it is -ve.
Acute phase response (active disease / inflammation):
- Erythrocyte sedimentation rate, ESR (↑)
- C-reactive protein, CRP (↑)
FBC:
- Hematocrit/Hg (↓)
- Platelets (↑)
- WBC (↑)
Radiologic (X-ray / MRI) – usually occur late in course of disease:
- Narrowing of joint space
- Erosion (around margin of joint)
- Hypertrophic synovial tissue
How to diagnose RA?
History, PE, labs, radiographs…
At least 4 of the following:
- Early Morning Stiffness ≥ 1 hour x ≥ 6 weeks
- Swelling of ≥ 3 joints x ≥ 6 weeks
- Swelling of wrist/ MCP/ PIP joints x ≥ 6 weeks
- Rheumatoid nodules
- +ve RF and/or anti-CCP tests
- Radiographic changes
What is goals of Tx for RA?
Achieve remission or low disease activity:
- At least 6 months
- Boolean 2.0 criteria (remission):
Tender Joint Count (TJC) ≤ 1
Swollen Joint Count (SJC) ≤ 1
CRP ≤ 1 mg/dL
Patient Global Assessment (PGA) using 10cm VAS: ≤ 2 cm
- Index based definition:
SDAI / CDAI / DAS 28
- Achieve maximal functional improvement
- Stop disease progression
- Prevent joint damage
- Control pain
What are the common pharmacotherapy given for RA?
- NSAIDs
- Glucocorticoids
- Disease modifying anti-rheumatic drugs (DMARDs):
Conventional/traditional DMARDs (csDMARDs)
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Biologic DMARDs (bDMARDs)
TNF-𝛼 inhibitor: etanercept, infliximab, adalimumab…
IL-6 receptor antagonist: tocilizumab
Anti-CD20 B-cell depleting monoclonal antibody: rituximab
Targeted synthetic DMARDs (tsDMARDs):
JAK inhibitors: tofacitinib, baricitinib…
What is NSAIDs place in therapy for RA?
- MOA: inhibition of prostaglandin synthesis (small portion of the inflammatory cascade)
- Do NOT alter the course of the disease
- Used as adjuncts to DMARD: relieve pain & minor inflammation (effect in 1-2 weeks), not rly LT Tx
- Comparable efficacy between NSAIDs vs COX-2 inhibitors
What is CS place in therapy for RA?
- MOA: anti-inflammatory & immunosuppressive properties
- Used as low-dose bridging therapy (PO prednisolone < 7.5 mg/day) when initiating DMARDs
- Used as continuous low-dose therapy for difficult-to-control patients.
NOT recommended due to SE & availability of many DMARD choices - Used to control flare (e.g. intraarticular injections).
May be repeated q 3 monthly, but not more than 2-3 x per year per joint (risk of tendon atrophy & accelerated joint destruction)
SE of CS
Osteoporosis
Insulin resistance
Gastric ulcer (if +NSAID)
Cataract/glaucoma
Incr CV risk
What is DMARDs place in therapy for RA?
Alters disease progression:
- Slow/prevent radiographic joint damage
- Improve physical function
- Lower ESR / CRP
How earlier should DMARDs be started?
Start soonest:
- Maximal joint damage within 1st two years
- 30% have radiographic erosions at diagnosis
- 60% by 2 years
Slow onset (weeks to months)
What is usually first line Tx for RA?
DMARDs should be started as soon as the diagnosis is made:
- MTX should be part of first Tx strategy -> v. effective + low cost
- Consider sulfasalazine/leflunomide if MTX is contraindicated or not tolerated
- Hydrochloroquine is best tolerated.
- Short-term glucocorticoids should be considered when initiating/changing DMARDs, but tapered & discontinued as rapidly as clinically feasible
How often should Tx be monitored for RA?
Monitor Frequently in active Disease (every 1-3 months)
Tx should be adjusted if no improvement by 3mth or target not reached by 6mth
For RA pts with mod-high disease activity, what is preferred?
- Methotrexate monotherapy preferred (established efficacy & safety as 1st line DMARD)
- Short-term low-dose glucocorticoid can be added to alleviate symptoms prior to onset of DMARD action
For RA pts with low disease activity, what is preferred?
- Hydroxychloroquine preferred (better tolerated)
- Sulfasalazine recommended over methotrexate (less immunosuppressive)
- Methotrexate recommended over leflunomide (greater dosing flexibility & lower cost)
What is the dosing of MTX for RA?
Initiation dose: 7.5 mg ONCE weekly
Dose increment 2.5 – 5 mg/week every 4-12 weeks based on response
Target dose: 15 mg/week within 4-6 weeks of initiation
1 tab: 2.5mg so means 1-2tabs increment per week.
Max 25 mg/week
What other drug should be given tgt with MTX?
Folic acid 5mg/week
What is sulfasalazine dose for RA?
Sulfasalazine: initiate w 500 mg OD or BD, increase by 500 mg/week → 1g BD (maintenance), max 3000 mg/day
What is hydroxychloroquine dose for RA?
Hydroxychloroquine: 200 – 400 mg in one or two divided doses (max 5 mg/kg/day)
What is leflunomide dose for RA?
Leflunomide: 100 mg/day x 3 days (optional loading dose), 20 mg/day (maintenance dose)
What can be given as bridging therapy when initiating DMARDs? What is the dose?
Short-term low-dose glucocorticoid (GC) can be added…
- When starting/changing DMARD for moderate/high RA disease activity
- E.g. ≤ 7.5 mg/day prednisolone up to 3 months
- BUT to be tapered and discontinued within 3 months
- BUT to be discontinued if bDMARD/tsDMARD started
