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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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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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 >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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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