Rheumatoid Arthritis

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Rheumatoid Arthritis

• Carole Callaghan
• Principal Pharmacist
• NHS Lothian

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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.

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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.

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Rheumatoid Arthritis

• A chronic systemic inflammatory disease,
  characterised by potentially deforming
  symmetrical polyarthritis and extra-articular
  features.

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Epidemiology

• prevalence approx. 1 in UK
• 31 ratio of femalesmales affected
• peak onset 40 and 50 years of age
• genetic, environmental and infective factors
  involved in disease development

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Pathogenesis

• cause remains unknown
• toxic substances found in synovium
• destruction of joints
• immunological disturbances identified
• RA is an autoimmune disease

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Pathology

• disease of the synovium
• inflammation due to infiltration of lymphocytes,
  macrophages etc
• proliferation of cells results in pannus
  formation

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Pathology
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Pathology
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Symptoms

• joint pain (usually worse on waking)
• morning stiffness (can vary in duration)
• general symptoms e.g. fatigue, malaise, bone
  ache

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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

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Signs
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Joint involvement

• hands/wrists
• elbows/shoulders
• cervical spine
• knees
• ankles/feet
• unpredictable pattern

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Investigation

• Imaging e.g. x-ray, ultrasound, MRI
• FBC and ESR
• Other tests e.g RhF, anti-CCP (antibodies)

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Management (1st stage)

• lifestyle maintain where possible
• multidisciplinary e.g.
• physiotherapy
• occupational therapy
• podiatry

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Management (2nd stage)

• relief of symptoms

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NSAIDs

• more effective than simple analgesics
• variation in response
• balance efficacy
• and toxicity

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NSAID toxicity

• related to dose and duration of therapy
• GI
• renal and cardiovascular
• elderly more at risk

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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

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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

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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??

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Management (3rd stage)

• long-term suppressive drug therapy with disease
  modifying anti-rheumatic drugs (DMARDs)

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Early DMARD

• stabilise joint function as early as possible
  better outcome
• greater awareness of NSAID toxicity
• DMARDs slow disease progression

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DMARDs

• efficacy .vs. toxicity
• methotrexate and sulfasalazine have the best
  efficacytoxicity ratio in meta-analyses
• Increased use of combination therapy TICORA,
  COBRA, BeST.
• better than sequential monotherapy

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DMARDs (cont)

• DAS28 (Disease Activity Score)
• -swollen joints
• -tender joints
• -ESR
• -patients general health score
• Monitoring
• -FBC
• -LFTs
• -UEs
• -BP
• -urinalysis

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Systemic corticosteroids

• not recommended for routine use
• if necessary, use lowest dose, shortest time
• monitor due to side effect profile

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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

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TNF a - Mode of Action
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Anti-TNF Biologics - Mode of Action
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TNF a

• 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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Effects of Blocking TNFa

• 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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B Cell Involvement in the Pathogenesis of RA
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Biologic Pathways
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Nomenclature

• -ximab Chimeric antibody
• -zumab Humanised antibody
• -umab Human antibody
• -cept Fusion protein

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Immunogenecity
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Eligibility Criteria for Biologic Therapy (BSR)

• DAS28 gt5.1
• At least 2 previous DMARDs
• Adequate response at 3 months
• 3-monthly monitoring

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Infection

• 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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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

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Other Infections

• Listeria/salmonella
• Varicella
• HBV/HCV
• HIV

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Vaccination

• Data limited
• Influenza and pnuemococcal
• recommended (many also on MTX)
• Hep B

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Malignancy

• 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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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

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Safety 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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Abatacept
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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
• Increase in efficacy after first year of treatment

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Tocilizumab
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Tocilizumab (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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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 outcome due May 2010

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Summary

• RA inflammatory destructive
• symptomatic relief
• early disease modification