ic16 rheumatoid arthritis management Flashcards
risk factors for RA
peak incidence 40-50 yo, more common in women
- family history
- genetics: HLA-DRB1 gene in MHC region = major genetic susceptibility
- smoking
what is the clinical presentation of rheumatoid arthritis?
1) pain
2) swelling
3) erythematous + warm
4) early morning stiffness >30min
5) SYMMETRICAL poly-arthritis usually with the small joints (MCP and PIP of hand; IP of thumb; wrist; MTP of toes)
also large joints (elbows, shoulders, hips, knees, ankles)
*MCP = metacarpal
*IP = intermediate phalanges
*PIP = proximal inter-phalanges
*MTP = meta-tarso-phalangeal
systemic symptoms of RA
1) generalised aching or stiffness
2) fatigue
3) fever
4) weight loss
5) depression
more present in disease onset >60 yo
what are the extra-articular complications of RA
eye: scleritis (inflammation of sclera), sjogren syndrome (dry eyes/mouth)
heart:** CAD**, AF, HF, myocarditis…
haematology: anemia, Felty’s syndrome (triad of RA, splenomegaly, granulocytopenia), lymphoproliferative disease (excessive production of lymphocytes)
lungs: pleural effusion (accumulation of fluid in the pleural space), interstitial lung disease
renal: glomerulonephritis, amyloidosis (amyloid build-up)
skin: rheumatoid nodules, neutrophilic dermatoses, skin ulcers
vascular: **rheumatoid vasculitis **(blood vessel inflammation), PVD
presentation of chronic RA
1) deformities
- swan neck, boutonniere
- z shaped thumb
- MCP subluxation (finger); MTP subluxation (toes)
- ulnar deviation
- rheumatoid nodules (elbow)
- popliteal cyst (fluid filled growth behind the knee)
2) loss of physical function and ability to carry out ADL
*subluxation = partial dislocation of joints with bones still touching.
lab findings for RA
1) autoantibodies (not all patients will have, only confirmatory if positive)
- RF
- anti-citrullinated peptide antibodies ACPA using anti-CCP assays
2) acute phase response (active disease/inflammation)
- ESR, CRP increase
3) FBC
- decreased Hg, increased platelets and WBC
4) radiology
- narrowing joint space, erosion, hypertrophic synovial tissue.
diagnosis of RA
AT LEAST 4 of the following
1) early morning stiffness ≥1h for ≥6wks
2) swelling of ≥3 joints for ≥6wks
3) swelling of wrist/MCP/PIP joints for ≥6 wks
4) rheumatoid nodules
5) positive RF and/or anti-CCP
6) radiographic changes
diagnosis of RA based on ACRA guidelines
≥6 out of 10 = confirmed diagnosis
when is disease remission
atleast 6 months with
boolean 2.0
- TJC , SJC ≤1
- CRP ≤1
- PGA using 10cm VAS ≤2cm
INDEXES
- SDAI ≤3.3
- CDAI ≤2.8
- DAS28 <2.6
NSAID use in RA?
normally used before diagnosis/confirmation of RA to manage pain and inflammation
DOES NOT ALTER COURSE OF DISEASE
GC use in RA
low dose bridging therapy
PO PREDNISOLONE <7.5MG/DAY
when initiating DMARDs or changing DMARDs
for up to 3 months (or when bDMARD/tsDMARD started)
with predefined tapering
use of continuous low dose therapy?
use for over 2 years
may be efficacious BUT risk of CV diseases, infections, fractures = not recommended
intra-articular GC use?
can be used to control monoarticular or oligoarticular flares via local injection
repeated q3 monthly
BUT no more than 2-3 times per year per joint due to risk of tendon atrophy and accelerated joint destruction…
what is the first line treatment for DMARDs
start csDMARDs to slow or prevent radiographic joint damage, improve physical function and lower ESR/CRP
For moderate to high disease
- MTX 1st choice
- Sulfasalazine or Leflunomide 2nd choice if MTX contra/not tolerated
For low disease activity
- can consider hydroxychloriquine without poor prognostic factors and other three are contraindicated
STARTED ASAP
frequency of disease monitoring
every 1-3 months
treatment should be adjusted if no disease improvement in 3 months and remission not reached by 6 months
what are poor prognostic factors
high disease activity (DAS28>3.2, SDAI>11, CDAI >10)
high ACPA or RF
high CRP
high TJC or SJC
presence of early erosions
failure of ≥2 csDMARDs
if treatment failure to csdmard?
if no poor prognostic factor
= consider adding another csDMARD or changing to a new csDMARD (can consider triple therapy)
if poor prognostic factor
= add bDMARD (1st choice)
= add tsDMARD (last choice)
MTX dose? + folic acid dose?
initiation: 7.5mg once weekly
increase 2.5-5mg/week every 4-12 weeks OR target 15mg/week in 4-6 weeks
max 25mg per week
ADD ON folic acid 5mg once weekly, taken the day after MTX dosing
sulfasalazine dosing
initiate 500mg OD-BD
increase by 500mg per week
maintenance = 1g BD
max 3g/day
hydroxychloroquine dosing
200-400mg in one-two divided doses
max 5mg/kg/day
leflunomide dosing
100mg/day for 3 days (loading dose)
and
20mg/day maintenance dose
dose adjustment for methotrexate
if AST/ALT >3xULN = 75% of dose
if CrCl 30-50ml/min = 50% of dose
if CrCl <30min/min = avoid use
it is 80% renally excreted unchanged
contraindications to methotrexate
preexisting liver disease
immunodeficiency syndrome
blood dyscrasia
DDi MTX
NSAIDs
PPI
probenecid
vaccines
alcohol
side effects of MTX
GI: nausea, diarrhoea, anorexia, stomatitis
Liver: increase transaminase, cirrhosis
Lung: fibrosis
Haem: myelosuppression
Derm: photosx, SJS/TEN
pregnancy status for MTX
DO NOT GIVE, teratogenic, embryo fetal toxicity
monitoring sx MTX
lUNG: sob, cough
GI: n/v, mouth sores, diarrhoea
liver: jaundice
Derm: toxicity
Infection
monitoring labs MTX
FBC
LFT = AST/ALT, albumin, bilirubin
SCr
sulfasalazine dose adjustments
eGFR <60 = lower dose
dialysis = (start at 50%) initiate at 250mg oD instead, up to 1g/day
metabolites excreted via urine
contraindications of sulfasalazine
sulfonamide allergy
caution in G6PD deficiency
side effects of sulfasalazine
N/V, headache, dyspepsia
rash
agranulocytosis
oligospermia (reversible)
urinary discolouration
sulfasalazine pregnancy status
risk B
monitoring for sulfasalasin sx and labs
sx: n/v, rash, infection
labs: FBC
hydroxychloriquine dose adjustments
only caution in renal or hepatic impairment
contraindications of hydroxychloroquine
preexisting retinopathy
caution in g6pd def
side effects of hydroxychloroquine
retinopathy
hypoglycaemia
qtc prolongation
rash
photosx
hyperpigmentation
headache dizziness, neuropsych sx
pregnancy risk for hydroxychloroquine
risk C
monitoring for hydroxychloroquine labs and sx
sx = nil
labs: EYE EXAM
leflunomide cyp interactions
cyp1a2 inducer (mod)
cyp2c8, BCRP, ABCG2, OATP1B1/1B3 inhibitor (mod)
undergoes enterohepatic recirculation = long t1/2 18-19 days
dose adjustment for leflunomide
alt > 2x ULN
- CONTRAINDICATED
CONTRAINDICATIONS for leflunomide
liver disease
immunodeficiency states
DDI leflunomide
cholestyramine
activated charcoal
rosuvastatin
warfarin
alcohol
vaccines
leflunomide SE
diarrhoea, nausea, headache
liver transaminase increase
alopecia
myelosuprresion
rash
pregnancy status for leflunomide
avoid RISK X pregnancy
monitoring of sx for leflunomide
diarrhoea
ahir loss
jaundice
infection
monitoring labs for leflunomide
FBC
LFT (ast/alt/albu/bili)
bMARDs and tsDMARDs in SG
adalimumab = SC admin (SDL)
infliximab = IV (SDL)
eternacept = SC (MAF)
tocilizumab = IV (MAF)
rituximab = IV (MAF)
tofacitinib = PO (MAF)
baricitinib = PO (MAF)
safety concerns with bDMARDs and tsDMARDs
1) injection site/infusion reaction
2) myelosuppression - monitor CBC with WBC differentials and platelet count
3) infections - URTI, TB, hepatitis, opportunistic infections
4) malignancy risk
5) autoimmune diseases - SLE? demyelinating peripheral neuropathies
6) CVD - HF, HTN
7) hepatic effect - increase LFT? aminotransferase
8) metabolic effect - hyperlipidemia - monitor lipids
9) pulmonary disease - pulmonary toxicity, caution in interstitial disease
10) GI perforation - evaluate abdo pain/repeat vomiting
11) thrombosis - avoid in pMH thrombotic events
selection of bdmard or tsdmard?
do not use more than 1
consider
- hypersx
- severe infections
- HEART FAILURE (SPECIFIC TO TNF BLOCKERS)
selection of tsDMARD? what are the risk factors for MACE and malignancy
1) CV factors
- obesity, smoking, PMH DM, HTN, >65yo
2) malignancy
- PMH malignancy
3) bleeding risk
- PMH MI, HF, blood clotting disorders,
- use of CHC, HRT
- undergoing major surgery
- immobility
what to do before initiating bDMARD or tsDMARD (general)
pre treatment
- screen for TB (latent or active); only start after completion of anti-TB TX
- hep B and C = avoid if untreated
vaccination
- Pneumococcal, influenza, hepB, varicella, herpes zoster
lab screening
- CBC w/ differentials for WBC, PLT count
- LFT : alt, ast, bilirubin, alp
- Lipid panel
- SCr
what is the end goal for RA
low disease activity or remission = do not discontinue DMARD abruptly, advised to continue all DMARDs rather than decrease dose/disocntinue
non phx management for RA
1) PATIENT EDUCATION = about disease and management and expctations
2) psychological interventions
- CBT to improve QOL
3) rest inflamed joint
4) physical activity and exercise
- swimming
- range of motion = preserve joint motion
- increase muscle strength, avoid contractures and muscle atrophy
- aerobic exercises = reduce pain, fatigue, improve sleep
**AVOID HIGH INTENSITY, WEIGHT BEARING EXERCISES
**
5) diet
- manage ASCVD risk
- possible to use fish oil to reduce inflammation
- weight management if obese
- overcome anorexia and poor dietary intake during RA disease course
specific MONITORING for IL6 and JAKi
high risk of gi perforation
increases with diverticulitis, >65yo, GC use, NSAID use
MONITOR for abdo pain, repeated vomiting
high risk of thrombosis, specifically with patients with PMH thrombotic events
- to monitor as well
specific contraindications for tnf alpha
avoid in heart failure esp nyha class 3 and 4
