core course lecture - rheumatoid arthritis
DESCRIPTION
Core course lecture - Rheumatoid Arthritis29 Jan 2008 Carole CallaghanTRANSCRIPT
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Pharmacy
Rheumatoid Arthritis
Carole Callaghan
Principal Pharmacist
NHS Lothian
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PharmacyAim
To update pharmacists on the current
management of rheumatoid arthritis and
explore ways to implement
pharmaceutical care for this patient group
as part of normal working practice.
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PharmacyObjectives
• Describe the common signs and symptoms associated with rheumatoid arthritis.
• Define the current therapeutic management for both the alleviation of symptoms and for modifying disease progression in rheumatoid arthritis.
• Identify pharmaceutical care issues and appropriate management solutions when responding to symptoms in patient scenarios.
• Explore how to implement the principles of a pharmaceutical care needs assessment tool in practice.
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PharmacyRheumatoid Arthritis
A chronic systemic inflammatory disease, characterised by potentially deforming
symmetrical polyarthritis and extra-articular features.
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PharmacyEpidemiology
• prevalence approx. 1% in UK
• 3:1 ratio of females:males affected
• peak onset 40 and 50 years of age
• genetic, environmental and infective factors involved in disease development
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PharmacyPathogenesis
• cause remains unknown
• toxic substances found in synovium
• destruction of joints
• immunological disturbances identified
• RA is an autoimmune disease
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PharmacyPathology
• disease of the synovium
• inflammation due to infiltration of lymphocytes, macrophages etc
• proliferation of cells results in ”pannus” formation
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PharmacyPathology
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PharmacyPathology
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PharmacySymptoms
• joint pain (usually worse on waking)
• morning stiffness (can vary in duration)
• general symptoms e.g. fatigue, malaise, bone ‘ache’
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PharmacySigns
• swelling
• tenderness
• reduced range of movement
• deformities (if untreated over long-term)
• extra-articular features e.g. nodules, anaemia of chronic disease, pleural effusion
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PharmacySigns
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PharmacyJoint involvement
• hands/wrists
• elbows/shoulders
• cervical spine
• knees
• ankles/feet
• unpredictable pattern
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PharmacyInvestigation
• Imaging e.g. x-ray, ultrasound, MRI
• FBC and ESR
• Other tests e.g RhF, anti-CCP (antibodies)
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PharmacyManagement (1st stage)
• lifestyle – maintain where possible
• multidisciplinary e.g.
– physiotherapy
– occupational therapy
– podiatry
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PharmacyManagement (2nd stage)
• relief of symptoms
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PharmacyNSAIDs
• more effective than simple analgesics
• variation in response
• balance efficacy
• and toxicity
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PharmacyNSAID toxicity
• related to dose and duration of therapy
– GI
– renal and cardiovascular
– elderly more at risk
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PharmacyGI toxicity
• well documented in literature
• identifiable risk factors e.g. age, previous history, other medication (steroids, warfarin), alcohol
• improved use secondary to identifying those at risk and using gastroprotection
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PharmacyNSAID summary
• use lowest dose compatible with symptom relief
• use gastroprotection in “at risk” patient
• reduce and, if possible, withdraw when good response from DMARD
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PharmacyCOX-2 Inhibitors
• selectively block COX-2 isoenzyme
• provide pain relief (as efficacious as NSAIDs)
• less GI bleeding than NSAIDs (less significant GI symptoms remain e.g. dyspepsia)
• CV risk??
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PharmacyManagement (3rd stage)
• long-term suppressive drug therapy with disease modifying anti-rheumatic drugs (DMARDs)
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PharmacyEarly DMARD
• stabilise joint function as early as possible = better outcome
• greater awareness of NSAID toxicity
• DMARDs slow disease progression
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PharmacyDMARDs
• efficacy .vs. toxicity
– methotrexate and sulfasalazine have the best efficacy:toxicity ratio in meta-analyses
• Increased use of combination therapy – TICORA, COBRA, BeST.
– better than sequential monotherapy
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PharmacyDMARDs (cont)
• DAS28 (Disease Activity Score)-swollen joints-tender joints-ESR-patient’s general health score
• Monitoring-FBC-LFTs-U&Es-BP-urinalysis
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PharmacySystemic corticosteroids
• not recommended for routine use
• if necessary, use lowest dose, shortest time
• monitor due to side effect profile
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PharmacyIntra-articular corticosteroids
• “target” joint i.e. one or two large joints affected, can avoid systemic steroid
• maximum number per joint/time – but no evidence for this theory
• evidence lacking for this practice,but patients report benefit
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PharmacyTNF -Mode of Action
ActivatedActivatedMacrophageMacrophage
TNFTNF
TargetTargetCellCell
SignalSignal
sTNFR
sTNFR
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Pharmacy
Anti-TNF Biologics - Mode of Anti-TNF Biologics - Mode of ActionAction
ActivatedActivated Macrophage TargetTargetCellCell
SignalSignalsTNFR
sTNFR
TNFTNF
TNFRTNFR
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PharmacyTNF
Three agents currently licensed in UK and
SMC approved:
infliximab (human antichimeric antibody)
etanercept (fusion protein)
adalimumab (fully humanised monocloncal antibody)
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PharmacyEffects of Blocking TNF
Immunology
RF, T cell function restored
Inflammation
Cytokine production in joints (IL1, IL6, TNF)
Angiogenesis
levels of angiogenesis
Joint destruction
damage to bone and cartilage
Haematology
platelets, fibrinogen, restoration of Hb
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Pharmacy
B Cell Involvement in the Pathogenesis of RA
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PharmacyBiologic Pathways
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PharmacyNomenclature
-ximab Chimeric antibody
-zumab Humanised antibody
-umab Human antibody
-cept Fusion protein
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PharmacyImmunogenecity
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Pharmacy
Eligibility Criteria for Biologic Therapy (BSR)
DAS28 >5.1
At least 2 previous DMARDs
Adequate response at 3 months
3-monthly monitoring
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PharmacyInfection
Do not initiate in presence of serious
active infection or in patients at high risk
Discontinue in presence of serious
infection
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PharmacyTuberculosis
Screen for TB
Active TB needs to adequately treated
Prophylactic anti-TB therapy for potential latent
disease
Monitor during/after biologic; treat if required
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PharmacyOther Infections
Listeria/salmonella
Varicella
HBV/HCV
HIV
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PharmacyVaccination
Data limited
Influenza and pnuemococcal
recommended (many also on MTX)
Hep B
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PharmacyMalignancy
No increased risk of solid tumours or
lymphoproliferative disease
Investigate/stop therapy
Caution in pre-malignant conditions
Preventative skin care/ongoing surveillance
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PharmacyRituximab
With MTX only (SMC restricted use)
Inadequate response or intolerant of other
DMARDs, including at least one anti-TNF
By specialists in accordance with criteria
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PharmacySafety with Rituximab
Delay post-anti-TNF
Check immunoglobulins
Re-treat on clinical signs
Active infection, severe immunocompromised
Screen for hepatitis (B & C)
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PharmacyAbatacept
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PharmacyAbatacept (contd)
Selective T cell co-stimulation modulator – blocks the co-stimulatory signal required for full T cell activation
Not recommended by SMC and reserved for refractory disease. However, this advise superseded by NICE MTA 195 and can now be used in anti-TNF or rituximab failure/intolerant
Increase in efficacy after first year of treatment
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PharmacyTocilizumab
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PharmacyTocilizumab (contd)
Recommended by SMC for combination
therapy only i.e. with MTX
ADRs e.g. liver enzymes, neutropenia,
lipids etc . . .
Place in therapy?
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PharmacyCertolizumab
Nanomolecule comprising a humanised antibody fragment against TNF alpha with a polyethylene glycol tail - designed to increase bioavailability
RCTs show rapid improvement in disease activity (ACR20) compared with placebo and methotrexate
SMC approved (in conjunction with patient access scheme)
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PharmacySummary
• RA = inflammatory & destructive
• symptomatic relief
• early disease modification