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Core course lecture - Rheumatoid Arthritis
 

Core course lecture - Rheumatoid Arthritis

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Core course lecture - Rheumatoid Arthritis

Core course lecture - Rheumatoid Arthritis
29 Jan 2008
Carole Callaghan

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    Core course lecture - Rheumatoid Arthritis Core course lecture - Rheumatoid Arthritis Presentation Transcript

    • Rheumatoid Arthritis Carole Callaghan Principal Pharmacist NHS Lothian
    • Aim
      • 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.
    • Objectives
      • 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.
    • Rheumatoid Arthritis
      • A chronic systemic inflammatory disease, characterised by potentially deforming symmetrical polyarthritis and extra-articular features.
    • Epidemiology
      • 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
    • Pathogenesis
      • cause remains unknown
      • toxic substances found in synovium
      • destruction of joints
      • immunological disturbances identified
      • RA is an autoimmune disease
    • Pathology
      • disease of the synovium
      • inflammation due to infiltration of lymphocytes, macrophages etc
      • proliferation of cells results in ”pannus” formation
    • Pathology
    • Pathology
    • Symptoms
      • joint pain (usually worse on waking)
      • morning stiffness (can vary in duration)
      • general symptoms e.g. fatigue, malaise, bone ‘ache’
    • Signs
      • swelling
      • tenderness
      • reduced range of movement
      • deformities (if untreated over long-term)
      • extra-articular features e.g. nodules, anaemia of chronic disease, pleural effusion
    • Signs
    • Joint involvement
      • hands/wrists
      • elbows/shoulders
      • cervical spine
      • knees
      • ankles/feet
      • unpredictable pattern
    • Investigation
      • Imaging e.g. x-ray, ultrasound, MRI
      • FBC and ESR
      • Other tests e.g RhF, anti-CCP (antibodies)
    • Management (1st stage)
      • lifestyle – maintain where possible
      • multidisciplinary e.g.
        • physiotherapy
        • occupational therapy
        • podiatry
    • Management (2nd stage)
      • relief of symptoms
    • NSAIDs
      • more effective than simple analgesics
      • variation in response
      • balance efficacy
      • and toxicity
    • NSAID toxicity
      • related to dose and duration of therapy
        • GI
        • renal and cardiovascular
        • elderly more at risk
    • GI 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
    • NSAID summary
      • use lowest dose compatible with symptom relief
      • use gastroprotection in “at risk” patient
      • reduce and, if possible, withdraw when good response from DMARD
    • COX-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??
    • Management (3rd stage)
      • long-term suppressive drug therapy with disease modifying anti-rheumatic drugs (DMARDs)
    • Early DMARD
      • stabilise joint function as early as possible = better outcome
      • greater awareness of NSAID toxicity
      • DMARDs slow disease progression
    • DMARDs
      • 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
    • DMARDs (cont)
      • DAS28 (Disease Activity Score)
      • - swollen joints
      • -tender joints
      • -ESR
      • -patient’s general health score
      • Monitoring
      • -FBC
      • -LFTs
      • -U&Es
      • -BP
      • -urinalysis
    • Systemic corticosteroids
      • not recommended for routine use
      • if necessary, use lowest dose, shortest time
      • monitor due to side effect profile
    • Intra-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
    • TNF  -  Mode of Action Activated Macrophage TNF Target Cell Signal sTNFR
    • Anti-TNF Biologics - Mode of Action Activated Activated Macrophage Target Target Cell Cell Signal Signal sTNFR sTNFR TNF TNF TNFR TNFR
    • TNF 
      • Three agents currently licensed in UK and
      • SMC approved:
      • infliximab (human antichimeric antibody)
      • etanercept (fusion protein)
      • adalimumab (fully humanised monocloncal antibody)
    • Effects 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
    • B Cell Involvement in the Pathogenesis of RA
    • Biologic Pathways
    • Nomenclature
      • -ximab Chimeric antibody
      • -zumab Humanised antibody
      • -umab Human antibody
      • -cept Fusion protein
    • Immunogenecity
    • Eligibility Criteria for Biologic Therapy (BSR)
      • DAS28 >5.1
      • At least 2 previous DMARDs
      • Adequate response at 3 months
      • 3-monthly monitoring
    • Infection
      • Do not initiate in presence of serious
      • active infection or in patients at high risk
      • Discontinue in presence of serious
      • infection
    • Tuberculosis
      • Screen for TB
      • Active TB needs to adequately treated
      • Prophylactic anti-TB therapy for potential latent
      • disease
      • Monitor during/after biologic; treat if required
    • Other Infections
      • Listeria/salmonella
      • Varicella
      • HBV/HCV
      • HIV
    • Vaccination
      • Data limited
      • Influenza and pnuemococcal
      • recommended (many also on MTX)
      • Hep B
    • Malignancy
      • No increased risk of solid tumours or
      • lymphoproliferative disease
      • Investigate/stop therapy
      • Caution in pre-malignant conditions
      • Preventative skin care/ongoing surveillance
    • Rituximab
      • 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
    • Safety with Rituximab
      • Delay post-anti-TNF
      • Check immunoglobulins
      • Re-treat on clinical signs
      • Active infection, severe immunocompromised
      • Screen for hepatitis (B & C)
    • Abatacept
    • Abatacept (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
    • Tocilizumab
    • Tocilizumab (contd)
      • Recommended by SMC for combination
      • therapy only i.e. with MTX
      • ADRs e.g. liver enzymes, neutropenia,
      • lipids etc . . .
      • Place in therapy?
    • Certolizumab
      • 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)
    • Summary
      • RA = inflammatory & destructive
      • symptomatic relief
      • early disease modification