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
SE of MTX?
Nausea, diarrhoea, myelosuppression, TEN, SJS, Increase transaminases
Can MTX be used in pregnancy?
NO, it is teratogenic
How to dose adjust MTX for RA?
- AS/ALT >3x ULN: 75% dose
- CrCl < 50: 50% dose
- CrCl < 30: avoid
MTX CI
Pre-existing liver disease, immunodef syndrome, blood dyscrasias
DDI with MTX?
NSAID/COX-2i, PPI, probenecid, vaccines, alcohol
What to monitor if pt on MTX?
FBC, LFT, SCr
Smx: SOB, cough, N/V, mouth sores, diarrhoea, jaundice, derm tox, infection
Sulfasalazine CI
Sulfonamide allergies
Caution in G6PD def
Which DMARDs can be used in pregnancy?
Sulfasalazine and hydroxychloroquine
Most impt SE of hydroxychloroquine?
Retinopathy
What to monitor if pt on sulfasalazine
FBC
Smx: N/V, rash, infection
When to avoid leflunomide?
ALT>2x ULT
Leflunomide SE
diarrhoea, increase transaminases, alopecia, myelosuppression
Can leflunomide be used in pregnancy?
No, it is teratogenic
What to monitor if pt on leflunomide?
FBC, LFT
Smx: diarrhoea, hair loss, jaundice, infection
DDI with leflunomide
Cholestyramine
Activated charcoal
Rosuvastatin
Warfarin
Vaccines
Alcohol
If pt is on MTX for RA but not at target, what can be added?
Add bDMARD or tsDMARD (can maximise improvement quickly)
Add hydroxychloroquine & sulfasalazine (“triple therapy”; less risk of adverse events & lower cost)
If pt on bDMARD/tsDMARD for RA but not at target, what can be done?
Switch to bDMARD or tsDMARD of a different class
How does bDMARD work in RA?
Binds to cytokines or their receptors to downregulate/inhibit their functions, which reduces immune & inflammatory responses
How does tsDMARD work in RA?
Binds to JAK proteins inside cells to prevent JAKs from transphosphorylating the associated cytokine & growth factor receptor
What are some safety concerns of using bDMARD and tsDMARDs?
Injection/infusion site rxns
Myelosuppression
Infections
Malignancy risk
Autoimmune disease
CVD
Hepatic effects
Metabolic effects
Pulmonary diseases
GI perforation
Thrombosis
What must you be careful when using bDMARD/tsDMARD?
- Do not use > 1 bDMARD/tsDMARD at the same time
- Consider contraindications during selection:
Hypersensitivity to components of the formulation
Severe infections e.g. sepsis, TB, opportunistic infections
HF (for TNF-𝛼 inhibitors) - Anti-drug antibodies (ADA) may occur with TNF-𝛼 inhibitors → loss of efficacy
- Switch to a bDMARD w a different MOA when one fails
- Switch to another after 3months if dont work.
Are bDMARD or tsDMARD preferred and why?
bDMARD preferred:
Tofacitinib carries higher risk for major adverse cardiovascular events (MACEs) & malignancy (compared to TNF-𝛼 inhibitors) for individuals with risk factors (below)
? similar risk with other JAK inhibitors
What must be done before initiating bDMARD/tsDMARD?
i.e screenings, vaccines, labs
Pre-treatment screening:
- Tuberculosis (latent/active): start after completing anti-TB Tx
- Hepatitis B & C: avoid if untreated disease detected
Vaccination required before initiation:
- Pneumococcal
- Influenza
- HepatitisB
- Varicella Zoster
Laboratory screening/monitoring:
- CBC w differential white count & platelet count
- LFT(ALT,AST,bilirubin,ALP)
- Lipid Panel
- SCr
If RA pt reaches target for >=6m, what should be done?
- Do NOT discontinue DMARD abruptly (may result in flares)
- Continuation of all DMARDS recommended over reduction of dose / gradual discontinuation, but…:
Triple therapy: gradual discontinuation of sulfasalazine is recommended over hydroxychloroquine (for lower adverse events & better tx persistence)
MTX + bDMARD/tsDMARD: gradual discontinuation of MTX is recommended (for better disease control)
- Usually MTX still remains.
What nonpharm should be educated to RA pts?
- Patient education regarding RA & management
- Psychosocial interventions e.g. CBT for enhancing self-efficacy / QoL
- Rest inflamed joint / use of splints to support joints & reduce pain:
Caution against promoting rest for fatigue symptoms → may lead to sedentary lifestyle - Physical activity & exercise e.g. swimming
Maintain range of joint motion:
Increase muscle strength → avoid contractures & muscle atrophy → can prevent decrease in joint stability → reduce fatigue & pain
Improve sleep
Avoid high-intensity weight-bearing exercises / activities - PT/OT (adherence, ensure exercise is done correctly)
- Nutritional & dietary counselling:
Weight management if obese
Dietary interventions for reducing inflammation e.g. fish oil (EPA/DHA ~ 5.5g daily?)
Dietary interventions for reducing ASCVD risk
