corecourselecture-phpapp01.ppt

8/10/2019 corecourselecture-phpapp01.ppt

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Educational Solutions for Workforce Development

Pharmacy

Rheumatoid Arthritis

Carole Callaghan

Principal Pharmacist

NHS Lothian


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PharmacyAim

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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PharmacyObjectives

Describe the common signs and symptoms associated with

rheumatoid arthritis.

Define the current therapeutic management for both thealleviation 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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PharmacyRheumatoid Arthritis

A chronic systemic inflammatory disease,

characterised by potentially deforming

symmetrical polyarthritis and extra-

articular features.


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PharmacyEpidemiology

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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PharmacyPathogenesis

cause remains unknown

toxic substances found in synovium

destruction of joints

immunological disturbances identified

RA is an autoimmune disease


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PharmacyPathology

disease of the synovium

inflammation due to infiltration of

lymphocytes, macrophages etc

proliferation of cells results in pannus

formation



PharmacyPathology



PharmacySymptoms

joint pain (usually worse on waking)

morning stiffness (can vary in duration)

general symptoms e.g. fatigue, malaise,

bone ache



PharmacySigns

swelling

tenderness

reduced range of movement

deformities (if untreated over long-term)

extra-articular features e.g. nodules,anaemia of chronic disease, pleural

effusion



PharmacySigns



PharmacyJoint involvement

hands/wrists

elbows/shoulders

cervical spine

knees

ankles/feet unpredictable pattern



PharmacyInvestigation

Imaging e.g. x-ray, ultrasound, MRI

FBC and ESR

Other tests e.g RhF, anti-CCP(antibodies)


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PharmacyManagement (1st stage)

lifestylemaintain where possible

multidisciplinary e.g.

physiotherapy

occupational therapy podiatry


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PharmacyManagement (2nd stage)

relief of symptoms


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PharmacyNSAIDs

more effective than simple analgesics

variation in response

balance efficacy

and toxicity


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PharmacyNSAID toxicity

related to dose and duration of therapy

GI

renal and cardiovascular

elderly more at risk


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PharmacyGI toxicity

well documented in literature

identifiable risk factors e.g. age,previous history, other medication(steroids, warfarin), alcohol

improved use secondary to identifyingthose at risk and using gastroprotection


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PharmacyNSAID 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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PharmacyCOX-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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PharmacyManagement (3rd stage)

long-term suppressive drug therapy with

disease modifying anti-rheumatic drugs(DMARDs)


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PharmacyEarly DMARD

stabilise joint function as early as

possible = better outcome

greater awareness of NSAID toxicity

DMARDs slow disease progression


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PharmacyDMARDs

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


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PharmacyDMARDs (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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PharmacySystemic corticosteroids

not recommended for routine use

if necessary, use lowest dose, shortest

time

monitor due to side effect profile


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PharmacyIntra-articular corticosteroids

target joint i.e. one or two large jointsaffected, can avoid systemic steroid

maximum number per joint/timebutno evidence for this theory

evidence lacking for this practice,

but patients report benefit


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PharmacyTNF a -Mode of Action

Activated

Macrophage

TNF

Target

Cell

Signal


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Pharmacy

Anti-TNF Biologics - Mode of

Action

ActivatedActivated Macrophage TargetTarget

CellCell

SignalSignal

TNFTNF


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PharmacyTNF 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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PharmacyEffects 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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PharmacyBiologic Pathways


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PharmacyNomenclature

-ximab Chimeric antibody

-zumab Humanised antibody

-umab Human antibody

-cept Fusion protein


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PharmacyImmunogenecity


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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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PharmacyInfection

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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PharmacyTuberculosis

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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PharmacyOther Infections

Listeria/salmonella

Varicella

HBV/HCV

HIV


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PharmacyVaccination

Data limited

Influenza and pnuemococcal

recommended (many also on MTX)

Hep B


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PharmacyMalignancy

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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PharmacyRituximab

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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PharmacySafety 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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PharmacyAbatacept


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PharmacyAbatacept (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


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PharmacyTocilizumab


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PharmacyTocilizumab (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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PharmacyCertolizumab

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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PharmacySummary

RA = inflammatory & destructive

symptomatic relief

early disease modification

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