IC16 RA Flashcards
main goal of treatment
Achieve disease remission
- at least 6 months
- Boolean 2.0 criteria (remission)
- Index based classification
pharmacotherapy approach in RA
- Glucocorticoid (ST use; bridging to DMARD)
- DMARDs (LT use)
non-pharmacological management strategies of RA
- physical activity & exercise (avoid high-intensity weight-bearing)
- PT/OT
- healthy diet to reduce CV risk & inflammation e.g. fish oil,
- weight management
what is RA
Chronic autoimmune INFLAMMATORY systemic disease
Prevalence of RA - age, gender
- Can occur at any age, peak at 40-50 y/o
- 3x more common in women
Genetic predisposition to RA
- HLA-DR1 or HLA-DR4 typing
- Parents are RF+
- Twin have RA
Clinical presentation of RA (KEY FEATURES)
- Inflammation (pain, swelling, redness, warmth)
- Early Morning stiffness > 30 mins
- Symmetrical polyarthritis
- Systemic sx (fever, aching/stiffness, etc)
- Extra-articular complications
Clinical presentation in CHRONIC RA
- deformities
- loss of physical fn & inability to carry out ADL
Radiologic finding - in late course of RA
- Narrowing of joint space
- Erosion (around margin of joint)
- Hypertrophic synovial tissue
Diagnosis of RA
At least 4 of the following:
- Early Morning Stiffness >/= 1 hour for > 6 weeks
- Swelling of >/= 3 joints for > 6 weeks
- Swelling of wrist/ MCP/ PIP joints for > 6 weeks
- Rheumatoid nodules
- +ve RF and/or anti-CCP tests
- Radiographic changes
Lab findings for RA - all stages of RA
- Autoantibodies (RF +ve, anti-CCP +ve)
- Acute phase response (Incr ESR & incr CRP)
- FBC (decr haematocrit, incr WBC & incr platelets)
Examples of csDMARD
- methotrexate
- sulfasalazine
- leflunomide
- hydroxychloroquine
Examples of tsDMARD (JAK inhibitor)
- tofacitinib, baricitinib
Examples of TNF-alpha inhibitor (bDMARD)
Etanercept, infliximab, adalimumab
Examples of IL6-receptor antagonist (bDMARD)
tocilizumab
Examples of anti-CD20 B cell depleting monoclonal antibody (bDMARD)
rituximab
Why is glucocorticoid not recommended for LT use?
Side effects
Indication for glucocorticoid
- Low dose bridging therapy when initiating/changing csDMARD (for moderate-high disease activity)
- Low-dose continuous therapy for difficult to control patients (but not recommended)
- Control flares (up to 2-3 injection per joint/ yr, q3 months)
MOA of glucocorticoid
anti-inflammatory & immunosuppressive ppty
Side effects of glucocorticoid
- osteoporosis, osteonecrosis
- impaired glucose metabolism, insulin resistance, beta cell dysfunction
- gastric ulcer (if concomitant NSAID)
- incr CV risk
- cataract, glaucoma
Do DMARDs alter disease progression?
Yes
Onset of DMARDs
Slow onset (weeks to months)
When to adjust tx for DMARD
- No improvement aft 3 months
- Target not reached aft 6 months
Monitoring frequency active disease
Every 1-3 months
DMARD therapy for moderate-severe RA disease activity
MTX + folic acid 5mg / week
+/- short-term GC
Dose for glucocorticoid
PO prednisolone < 7.5mg/day
DMARD therapy for low RA disease activity
In order of preference:
- Hydroxychloroquine (better tolerated)
- Sulfasalazine (less immunosuppressive)
- MTX (low cost)
- Leflunomide
MTX dose (initiation, increment, target, max)
- Initiation: 7.5mg once weekly
- Dose increment: 2.5-5mg every 4-12 wks based on response
- Target: 15mg/week (within 4-6 wks of initiation)
- Max dose: 25mg/week
MTX tablet strength
2.5mg
How long is GC added to DMARD for bridging
up to 3 months
Can GC be used in bDMARD/tsDMARD?
No
Renal/ liver dose adj: MTX
- AST/ALT > 3xULN: 75% of dose
- CrCl < 50 ml/min: 50% of dose
- CrCl < 30 ml/min: avoid use
Monitoring (sx & labs): MTX
Infection -like sx, jaundice, skin blisters;
FBC, LFT (AST,ALT,albumin, bilirubin), SCr
csDMARD C/I pregnancy
MTX, leflunomide
Which csDMARD could cause retinopathy?
Hydroxychloroquine
Drugs to use when not at target with MTX
- Add bDMARD or tsDMARD (maximise improvements)
or - Add Sulfasalazine & leflunomide (triple therapy; less adverse effects & lower cost)
Approach when patients with bDMARD/ tsDMARD but not at target
Switch to bDMARD or tsDMARD of a different class
General MOA of bDMARD
Binds to cytokine or their receptors to downregulate / inhibit their fn -> reduce immune & inflammatory responses
Administration route of bDMARD
SC inj/ IV infusion
Administration route of tsDMARD
Oral
C/I sulfasalazine
- sulfonamide allergy
- G6pd deficiency
C/I hydroxychloroquine
- pre-existing retinopathy
- g6pd deficiency
MOA of tsDMARD
Binds to JAK proteins inside cells to prevent JAKs from transphosphorylating the associated cytokine & growth factor receptor
JAK MEANING
Janus kinase (small molecule kinase)
-cept meaning
fusion of receptor to Fc region of IgG1
Which DMARDs cannot be used tgt
bDMARD and tsDMARD
Which DMARD to avid in HF (NYHA class III & IV)
TNF-alpha inhibitors
Anti-drug antibodies (ADA) may occur with ____, leading to loss of efficacy
TNF-𝛼 inhibitor
bDMARD or tsDMARD is preferred? why
bDMARD; tsDMARD more adverse effects (MACE, malignancy)
Pre-tx screening prior bDMARD/tsDMARD initiation
- TB
- HepB & C
Vaccination required prior bDMARD/tsDMARD initiation
- Pneumococcal
- Influenza
- Hepatitis B
- Varicella zoster
Lab screening/ monitoring prior starting ts/bDMARD
- CBC w differential white count & platelet count
- LFT(ALT,AST,bilirubin,ALP)
- Lipid panel
- SCr
When is RA considered low disease activity or remission
patients at target for >/= 6 months
