Pharmacy
Rheumatoid Arthritis
Carole Callaghan
Principal Pharmacist
NHS Lothian
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Aim
Pharmacy
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
Pharmacy
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
Pharmacy
A chronic systemic inflammatory disease,
characterised by potentially deforming
symmetrical polyarthritis and extraarticular features.
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Epidemiology
Pharmacy
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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Pathogenesis
cause remains unknown
toxic substances found in synovium
destruction of joints
immunological disturbances identified
RA is an autoimmune disease
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Pharmacy
Pathology
disease of the synovium
inflammation due to infiltration of
lymphocytes, macrophages etc
proliferation of cells results in pannus
formation
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Pharmacy
Pathology
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Pharmacy
Pathology
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Pharmacy
Symptoms
Pharmacy
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
Pharmacy
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
Pharmacy
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Joint involvement
hands/wrists
elbows/shoulders
cervical spine
knees
ankles/feet
unpredictable pattern
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Pharmacy
Investigation
Imaging e.g. x-ray, ultrasound, MRI
FBC and ESR
Other tests e.g RhF, anti-CCP
(antibodies)
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Pharmacy
Management (1st stage)
lifestyle maintain where possible
multidisciplinary e.g.
physiotherapy
occupational therapy
podiatry
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Pharmacy
Management (2nd stage)
relief of symptoms
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Pharmacy
NSAIDs
Pharmacy
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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Pharmacy
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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Pharmacy
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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Pharmacy
COX-2 Inhibitors
Pharmacy
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)
Pharmacy
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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Pharmacy
DMARDs
Pharmacy
efficacy .vs. toxicity
methotrexate and sulfasalazine have
the best efficacy:toxicity ratio in metaanalyses
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
-U&Es
-BP
-urinalysis
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Pharmacy
Systemic corticosteroids
not recommended for routine use
if necessary, use lowest dose, shortest
time
monitor due to side effect profile
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Pharmacy
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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Pharmacy
TNF a - Mode of Action
Activated
Macrophage
Pharmacy
Target
Cell
Signal
TNF
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Anti-TNF Biologics - Mode of
Action
Activated Macrophage
Pharmacy
Target
Cell
Signal
TNF
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TNF a
Pharmacy
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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Pharmacy
B Cell Involvement in the
Pathogenesis of RA
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Pharmacy
Biologic Pathways
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Pharmacy
Nomenclature
-ximab
Chimeric antibody
-zumab
Humanised antibody
-umab
Human antibody
-cept
Fusion protein
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Pharmacy
Immunogenecity
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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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Pharmacy
Infection
Pharmacy
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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Pharmacy
Other Infections
Listeria/salmonella
Varicella
HBV/HCV
HIV
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Pharmacy
Vaccination
Data limited
Influenza and pnuemococcal
recommended (many also on MTX)
Hep B
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Pharmacy
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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Pharmacy
Rituximab
Pharmacy
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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Pharmacy
Abatacept
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Pharmacy
Abatacept (contd)
Pharmacy
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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Tocilizumab
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Pharmacy
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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Pharmacy
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)
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Pharmacy
Summary
RA = inflammatory & destructive
symptomatic relief
early disease modification
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Pharmacy
