Rheumatoid Arthritis: Carole Callaghan Principal Pharmacist NHS Lothian

Pharmacy
Rheumatoid Arthritis
Carole Callaghan
Principal Pharmacist
NHS Lothian
Educational Solutions for Workforce Development
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.
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.
Rheumatoid Arthritis
Pharmacy
A chronic systemic inflammatory disease,

characterised by potentially deforming
symmetrical polyarthritis and extraarticular features.
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
Pathogenesis
cause remains unknown

toxic substances found in synovium
destruction of joints
immunological disturbances identified
RA is an autoimmune disease
Pharmacy
Pathology
disease of the synovium
inflammation due to infiltration of
lymphocytes, macrophages etc
proliferation of cells results in pannus

formation
Pharmacy
Pathology
Pharmacy
Pathology
Pharmacy
Symptoms
Pharmacy
joint pain (usually worse on waking)

morning stiffness (can vary in duration)
general symptoms e.g. fatigue, malaise,

bone ache
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
Signs
Pharmacy
Joint involvement
hands/wrists
elbows/shoulders
cervical spine
knees
ankles/feet
unpredictable pattern
Pharmacy
Investigation
Imaging e.g. x-ray, ultrasound, MRI
FBC and ESR
Other tests e.g RhF, anti-CCP
(antibodies)
Pharmacy
Management (1st stage)

lifestyle maintain where possible
multidisciplinary e.g.
physiotherapy
occupational therapy
podiatry
Pharmacy
Management (2nd stage)
relief of symptoms
Pharmacy
NSAIDs
Pharmacy
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
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
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
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??
Management (3rd stage)
Pharmacy
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
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
DMARDs (cont)
DAS28 (Disease Activity Score)
-swollen joints
-tender joints
-ESR
-patients general health score
Monitoring
-FBC
-LFTs
-U&Es
-BP
-urinalysis
Pharmacy
Systemic corticosteroids
not recommended for routine use
if necessary, use lowest dose, shortest
time
monitor due to side effect profile
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
Pharmacy
TNF a - Mode of Action

Activated
Macrophage
Pharmacy
Target
Cell
Signal
TNF
Anti-TNF Biologics - Mode of

Action
Activated Macrophage
Pharmacy
Target
Cell
Signal
TNF
TNF a
Pharmacy
Three agents currently licensed in UK and

SMC approved:
infliximab (human antichimeric antibody)
etanercept (fusion protein)
adalimumab (fully humanised
monocloncal antibody)
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
Pharmacy
B Cell Involvement in the

Pathogenesis of RA
Pharmacy
Biologic Pathways
Pharmacy
Nomenclature
-ximab
Chimeric antibody
-zumab
Humanised antibody
-umab
Human antibody
-cept
Fusion protein
Pharmacy
Immunogenecity
Pharmacy
Eligibility Criteria for Biologic Therapy

(BSR)
DAS28 >5.1
At least 2 previous DMARDs
Adequate response at 3 months
3-monthly monitoring
Pharmacy
Infection
Pharmacy
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
Pharmacy
Other Infections
Listeria/salmonella
Varicella
HBV/HCV
HIV
Pharmacy
Vaccination
Data limited
Influenza and pnuemococcal
recommended (many also on MTX)
Hep B
Pharmacy
Malignancy
No increased risk of solid tumours or
lymphoproliferative disease
Investigate/stop therapy
Caution in pre-malignant conditions
Preventative skin care/ongoing surveillance
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
Safety with Rituximab

Delay post-anti-TNF
Check immunoglobulins
Re-treat on clinical signs
Active infection, severe immunocompromised
Screen for hepatitis (B & C)
Pharmacy
Abatacept
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
Tocilizumab
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?
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)
Pharmacy
Summary
RA = inflammatory & destructive

symptomatic relief
early disease modification
Pharmacy

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Pharmacy

To update pharmacists on the current

Educational Solutions for Workforce Development

Describe the common signs and symptoms associated with

Educational Solutions for Workforce Development

A chronic systemic inflammatory disease,

Educational Solutions for Workforce Development

Educational Solutions for Workforce Development

cause remains unknown

Educational Solutions for Workforce Development

proliferation of cells results in pannus

Educational Solutions for Workforce Development

Educational Solutions for Workforce Development

joint pain (usually worse on waking)

general symptoms e.g. fatigue, malaise,

Educational Solutions for Workforce Development

Educational Solutions for Workforce Development

Educational Solutions for Workforce Development

Management (1st stage)

Educational Solutions for Workforce Development

Management (2nd stage)

Educational Solutions for Workforce Development

more effective than simple analgesics

improved use secondary to identifying

Educational Solutions for Workforce Development

selectively block COX-2 isoenzyme

Management (3rd stage)

long-term suppressive drug therapy with

Educational Solutions for Workforce Development

DMARDs slow disease progression

Educational Solutions for Workforce Development

efficacy .vs. toxicity

monitor due to side effect profile

Educational Solutions for Workforce Development

TNF a - Mode of Action

Educational Solutions for Workforce Development

Anti-TNF Biologics - Mode of

Educational Solutions for Workforce Development

Three agents currently licensed in UK and

Educational Solutions for Workforce Development

Effects of Blocking TNFa

Educational Solutions for Workforce Development

B Cell Involvement in the

Educational Solutions for Workforce Development

Educational Solutions for Workforce Development

Educational Solutions for Workforce Development

Eligibility Criteria for Biologic Therapy

Do not initiate in presence of serious

Educational Solutions for Workforce Development

Educational Solutions for Workforce Development

With MTX only (SMC restricted use)

By specialists in accordance with criteria

Educational Solutions for Workforce Development

Safety with Rituximab

Educational Solutions for Workforce Development

Selective T cell co-stimulation modulator

Educational Solutions for Workforce Development

RA = inflammatory & destructive