Rheumatoid arthritis Flashcards
ACR/EULAR 2010 criteria for RA
Number of joints involved. The more joints, the more points.
Serology
- RF, Anti-CCP
Acute phase reactant
- CRP, ESR
Duration of symptoms
≥6 weeks
A score of ≥6 = definite RA
Serology for RA
RF
Positive in 70% RA
Low specificity
More severe disease, more extra-articular complications e.g. nodules, vasculitis, lung
Anti-CCP Specificity >90% Correlate with RF Sensitivity 60-80% Precede onset and an important predictor of development of RA More severe disease, ILD, CV disease
Extraarticular features of RA
7 organ systems
1) Skin
Rheumatoid nodules
Vasculitis - small and medium sized vessels; poor prognosis
Ulcers
2) Eyes
Episcleritis/scleritis
Secondary Sjogren’s syndrome
3) Lungs Pleuritis/pleural effusion Pulmonary nodules +/- cavitation ILD - NSIP, UIP Bronchiectasis Cryptogenic organising pneumonia
4) Cardiovascular Premature atherosclerosis/CVD/PVD Pericarditis/pericardial effusion Arrhythmias Myocarditis HFpEF Cardiac nodules
5) Renal
Glomerulonephritis (usually mesangioproliferative)
Proteinuria
6) Liver
Liver nodules/hyperplasia
Portal fibrosis
7) Haem Lymphadenopathy Felty's syndrome - splenomegaly, leukopenia, LL ulceration, hyperpigmentation Lymphoma Amyloidosis Cryoglobulinemia
What is the most important drug in RA?
MTX Everyone should get MTX unless there is - Mild, seronegative disease - Renal impairment - Liver disease - High ETOH - Lung disease
Concomitant folic acid
Subcut better than PO
Monitor FBC, Cr, LFTs
Does everyone with RA need treatment?
YES 90% progressive disease Damage occurs early with loss of BMD in first year Disability occurs early Spontaneous remission is rare
Vaccination for RA
Hep B
Pneumococcus
Annual fluvax
HPV
VZV recommended age >50
- Shingrix available
- Should be given before biologics or tofacitinib
- Can give to patients on MTX and Arava
No live vaccines (yellow fever, MMR, BCG, Rubella) on biologics or MTX or Arava or Pred >10mg
*Vaccinate before they go on drugs
MTX lung disease
Fever, SOB, non-productive cough, pleuritic chest pain
Pulmonary crackles
Hypoxia, reduced DLCO
Acute interstitial and alveolar often bibasally
DDx: opportunistic infection
Mx: discontinue MTX, steroids
Majority recover completely
MTX and malignancy
Increased incidence of lymphoma
Stop MTX before surgery?
No
MTX hepatotoxicity associated with
Strong association with
ETOH
Preexisting liver disease
Renal insufficiency
Probable association
Duration
Cumulative disease
Obesity and diabetes
Lefulonamide MOA and efficacy in RA
Pyrimidine synthesis inhibitor –> kills T cells
Response rate similar to MTX
Takes 3/12 to work
Reduces joint damage
AE lefluonamide
Peripheral neuropathy - must cease drug. Need to do cholestyramine wash out.
Diarrhoea, hair loss
Pneumonitis
Criteria for biologics
Must have tried
MTX for 3/12
A second DMARD for 3/12
So can’t trial DMARD for at least 6/12
TNFi in RA
Completely turns off joint damage even if there is active disease (radiologically)
BUT TNFi has clinically the same effect as MTX
Any biologics + MTX work better than single therapy alone
When combined with MTX, all biologics/treatment specific DMARDs have similar efficacy when used as a first treatment strategy in early RA
Only 70% will get a good response
<50% will go into remission
What to do before starting TNFi?
Screen for latent TB, hep B, C, HIV
Vaccinate
How to do TB screening before TNFi?
Quantiferon gold
Mantoux
If patients come in with weight loss, feeling unwell after starting TNFi, they have TB until proven otherwise, even if quantiferon gold negative.
AE TNFi
Infections e.g. TB
Demyelination
- Avoid in those with MS 1st degree relatives
Malignancies
- Non-melanoma skin cancers, lymphoma (children)
Autoantibodies (ANA, dsDNA)
Drug-induced lupus
Hepatotoxicity
Uncommon
Vasculitis
Psoriasis
Sarcoidosis
Generally well tolerated
All work better with MTX
Abatacept MOA and use in RA
MOA: Ig binds to B7 (CD80/86) on APC so it can’t bind to CD28 on T cell = block constimulation
Only approved in combination with MTX
More effective in anti-CCP positive
Tocilizumab MOA and use in RA
Humanised anti-IL6 receptor antibody
Only biologic that is clinically more efficacious than MTX as monotherapy
Superior to TNFi as monotherapy but not better than TNFi + MTX
Consider after failure of multiple TNFi
AE Tocilizumab
Increased infections including TB reactivation Infusion reactions Bowel perforation Lipid elevations Neutropenia LFTs derangement
Can’t look at CRP! Will be normal even in sepsis.
More side effects than TNFi so we don’t go to this straight away
Rituximab MOA and use in RA
Anti-CD20 ab
Depletes B cells. Plasma cells spared.
Produces significant and sustained improvement in disease outcome for many months
Only available with MTX
Use in patients with malignancy or have failed TNFi
Useful in rheumatoid lung disease
Don’t use in hep B
JAK inhibitors AE
Infection; reactivation of TB Herpes zoster Cytopenias Hyperlipidaemia Malignancy CV disease Venous thromboses
JAK inhibitors MOA
Small molecules that inhibit JAK and ILD
JAK 1 inhibitor - helpful for RA
JAK 2 and 3 - side effects
More effective with MTX
Quick onset of action
Tofacitinib (JAKi) AEs
Dirty drug like tocilizumab (IL6 inhibition)
On top of class AEs there are
Transaminitis
Increased serum Cr
Bowel perforation (avoid in severe diverticulitis)
Which biologics can be used in pregnancy and breastfeeding?
TNFi
Best data is with certoluzimab (don’t cross placenta)
But try and avoid in 3rd trimester because then the baby shouldn’t have live vaccines (6 month rotavirus, MMR, varicella)
Baracitinib (JAKi) use in RA
Baracitinib + MTX is the most potent combination we have
Better than TNFi + MTX
JAK1 and 2 inhibitor
Not much pregnancy data
Increased thromboses
Mild increase creatinine and lipids
Upadacitinib (JAKi)
Upadacitinib + MTX is the other most potent combination we have
Better than TNFi + MTX
JAK 1 inihibitor
Not much pregnancy data
Mild increase in creatinine and lipids
Do they stay on biologics forever?
Likely
Very hard to get them off it
Biologics pre-op
Cease 1-2 treatment cycles prior
E.g. Etanercept 2 weeks, adalimumab 2-4 weeks
Restart when wounds healed
Rituximab when B cells normal
Minor surgery no need for cessation
Hep C
Which biologic to choose?
Etanercept
Untreated chronic hep B
Which biologic to choose?
No biologic recommended
Treated solid malignancy <5 years or treated
melanoma
Which biologic to choose?
Rituximab
Treated solid malignancy >5 years
Which biologic to choose?
Any biologic
Is combination therapy better in RA?
YES
MTX + SSZ + HCQ better than SSZ + HCQ or MTX alone
But these days if ineffective on 2 csDMARDS for 6/12, we go to biologics (probably 50% will need biologics)
Main cause of reduced life expectancy in RA
Increased cardiovascular risk (from uncontrolled inflammation)
Risk factors for developing RA
Genetic factors
HLADRB1
Smoking
Peridontal disease
Main cytokines involved in RA
TNF-alpha
IL1
IL6
IL17
Pro-inflammatory
Activate synovial fibroblasts, osteoclasts –> bone and cartilage damage
Pattern of joint involvement in RA
Morning stiffness +++
Symmetrical, bilateral
Small joints affected first
MCP, PIP (spares DIP; affected in p`soriatic arthritis, OA)
C spine (atlanto-axial subluxation; C1-C2 instability)
Wrist synovitis/radial deviation of wrist and ulnar deviation of fingers at MCPs/CTS
Swan neck deformity
Boutonniere deformity
Hindfoot and forefoot synovitis/MTPs affected (“walking on marbles”)
Radiology findings of RA
Periarticular soft tissue swelling (joint effusion, tenosynovitis)
Juxta-articular osteoporosis
Bone erosions
Joint space narrowing
Deformities in advanced disease - subluxation
When is prednisolone useful in RA?
Useful to give pred for a few weeks (maximum 4-5/12) for bridging until DMARD efficacy reached (4-6/52 usually), or for flares
Rituximab AEs
Infection (especially if low Ig)
Infusion reaction
Reduced response to vaccine
Reactivation of hep B
Treatment for RA 1st line 2nd line 3rd line Remission phase
1st line: MTX and short-term glucocorticoid
2nd line: Continue csDMARD and add a bDMARD/tsDMARD
3rd line: Use other bDMARD or tsDMARD in combination with existing csDMARD
Move down the ladder until target reached. Once in remission phase, consider weaning therapy or spacing out treatments more.
Which bDMARD is best in RA?
Similar efficacy despite different MOA
Always combine with MTX!
What do you expect RF and HLAB27 to be in seronegative spondyloarthritis?
RF negative
HLAB27 positive
Features of inflammatory back pain
Onset <45 years
> 3 consecutive months
Alternating buttock pain
Awaken at night particularly 2nd half of night, improves on arising
Responds to NSAIDs
Axial spondyloarthritis clinical features
Axial features
- Inflammatory back/buttock pain (sacroiliitis), restriction in spinal movement
Extra-axial features
- Peripheral arthritis (asymmetric, oligoarthritis of LL, enthesitis)
Extra-articular features
- Anterior uveitis (unilateral)
- IBD, psoriasis, apical fibrosis, AR
Diagnostic criteria for AS (ACAS classification criteria)
Sacroilitis on imaging and ≥1 SpA feature
HLAB27 and ≥2 SpA features
SpA features
- Inflammatory back pain
- Arthritis
- Enthesitis (heel)
- Uveitis
- Psoriasis
- Crohn’s/colitis
- Good response to NSAIDs
- HLAB27
- Elevated CRP
What’s the difference between non-radiographic axial spondyloarthropathy vs AS?
Spectrum of the same disease
85% Non-radiographic axial spondyloarthropathy will eventually progress to AS
…% of HLAB27+ will develop AS
5%
…% of AS has HLAB27+
> 90%
What imaging should you do in suspected AS?
Xray (takes months-years to evolve)
Sacro-iliac joints
Cervical, thoraco-lumbar spine
MRI
Management of AS
Back pain and stiffness
1st line: NSAIDs (minimum 12 weeks), non-pharmacological tx
2nd line: TNF-alpha blocker or IL-17 blocker (Secukinumab)
Peripheral arthritis
1st line also includes local steroids, DMARDs (MTX, sulfasalazine)
How to qualify for biological therapy (2nd line) in AS?
Must have trialled 12/52 NSAIDs and exercise
Do people need to have psoriasis to have psoriatic arthritis?
No
Clinical features of psoriatic arthritis
Asymmetric oligoarthritis (most common)/monoarthritis/polyarthritis
DIP and PIP joints
Can also have spondyloarthritis like AS
Dactylitis (sausage digits)
Nail disease (pitting, onycholysis, nail plate crumbling)
Arthritis mutilans (complete destruction of involved joint –> looks like a telescope)
Enthesitis (achilles tendon, plantar fascia)
RF and CCP in Psoriatic arthritis
Negative
Management of psoriatic arthritis
NSAIDs
csDMARDs - MTX, sulfasalazine, lefluonamide
Anti-TNF - infliximab, adalimumab, etanercept, golimumab, certolizumab
Anti-IL17 - secukinumab, ixekizumab
Anti-p40 subunit IL12/23 - ustekinumab
Causes of reactive arthritis
Genito-urinary infection - chlamydia trachomatis
GI infection - girardia, salmonella, campylobacter, yersinia
Reactive arthritis clinical presentation
Classic triad (Reiter's syndrome): arthritis, urethritis, conjunctivitis = can't see, can't pee, can't climb a tree
Asymmetric, oligoarticular, lower limb
Enthesitis
Dactylitis
Sacro-ilitis
Treatment of IBD associated spondyloarthritis
NSAIDs
DMARDs e.g. sulfasalazine; peripheral disease only, not axial
Anti-TNF
Controlling bowel disease
Ab associated with SLE
ANA dsDNA Anti-histone Anti-SM (most specific) Low C3/C4
Ab associated with Sjogren’s
Anti-Ro
Anti-La
ANA
Ab associated with mixed CT disease
Anti-RNP
Ab associated with scleroderma
ANA
Anti-Scl70 (diffuse)
Anti-centromere (limited)
RNA polymerase III (renal crisis)
Ab associated with myositis
ANA
Anti-Jo1 (anti-synthetase syndrome)
Anti-HMG Co-A reductase ab (statin induced ISMN)
Ab associated with RA
RF
Anti-CCP
don’t repeat testing
Not markers of disease activity
Ab associated with GPA
c-ANCA (PR3)
Ab associated with MPA
p-ANCA (MPO)
Ab associated with EGPA
p-ANCA (MPO)
What is the one drug that men trying to conceive should avoid?
Cyclophosphamide
Is tacrolimus and cyclophosphamide safe in pregnancy?
Yes
Are TNFi safe in pregnancy?
Yes
The only biologics that are safe
Should you continue csDMARDs and bDMARDs peri-op?
Continue csDMARDs e.g. MTX
Hold bDMARDS e.g. rituximab
In mild SLE, should you hold rheumatic medications peri-op?
Yes
Hold 1/52 before surgery
In severe SLE, should you hold rheumatic medications peri-op?
No
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