Rheumatoid Arthritis

Educational Solutions for Workforce Development

Pharmacy

Rheumatoid Arthritis

Carole Callaghan

Principal Pharmacist

NHS Lothian


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.


PharmacyObjectives

• 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.


PharmacyRheumatoid Arthritis

A chronic systemic inflammatory disease, characterised by potentially deforming

symmetrical polyarthritis and extra-articular features.


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


PharmacyPathogenesis

• cause remains unknown

• toxic substances found in synovium

• destruction of joints

• immunological disturbances identified

• RA is an autoimmune disease


PharmacyPathology

• disease of the synovium

• inflammation due to infiltration of lymphocytes, macrophages etc

• proliferation of cells results in ”pannus” formation


PharmacyPathology


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)


PharmacyManagement (1st stage)

• lifestyle – maintain where possible

• multidisciplinary e.g.

– physiotherapy

– occupational therapy

– podiatry


PharmacyManagement (2nd stage)

• relief of symptoms


PharmacyNSAIDs

• more effective than simple analgesics

• variation in response

• balance efficacy

• and toxicity


PharmacyNSAID toxicity

• related to dose and duration of therapy

– GI

– renal and cardiovascular

– elderly more at risk


PharmacyGI 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


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


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??


PharmacyManagement (3rd stage)

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


PharmacyEarly DMARD

• stabilise joint function as early as possible = better outcome

• greater awareness of NSAID toxicity

• DMARDs slow disease progression


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


PharmacyDMARDs (cont)

• DAS28 (Disease Activity Score)-swollen joints-tender joints-ESR-patient’s general health score

• Monitoring-FBC-LFTs-U&Es-BP-urinalysis


PharmacySystemic corticosteroids

• not recommended for routine use

• if necessary, use lowest dose, shortest time

• monitor due to side effect profile


PharmacyIntra-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


PharmacyTNF -Mode of Action

ActivatedActivatedMacrophageMacrophage

TNFTNF

TargetTargetCellCell

SignalSignal

sTNFR

sTNFR


Pharmacy

Anti-TNF Biologics - Mode of Anti-TNF Biologics - Mode of ActionAction

ActivatedActivated Macrophage TargetTargetCellCell

SignalSignalsTNFR

sTNFR

TNFTNF

TNFRTNFR


PharmacyTNF

Three agents currently licensed in UK and

SMC approved:

infliximab (human antichimeric antibody)

etanercept (fusion protein)

adalimumab (fully humanised monocloncal antibody)


PharmacyEffects of Blocking TNF

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


PharmacyBiologic Pathways


PharmacyNomenclature

-ximab Chimeric antibody

-zumab Humanised antibody

-umab Human antibody

-cept Fusion protein


PharmacyImmunogenecity


Pharmacy

Eligibility Criteria for Biologic Therapy (BSR)

DAS28 >5.1

At least 2 previous DMARDs

Adequate response at 3 months

3-monthly monitoring


PharmacyInfection

Do not initiate in presence of serious

active infection or in patients at high risk

Discontinue in presence of serious

infection


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


PharmacyOther Infections

Listeria/salmonella

Varicella

HBV/HCV

HIV


PharmacyVaccination

Data limited

Influenza and pnuemococcal

recommended (many also on MTX)

Hep B


PharmacyMalignancy

No increased risk of solid tumours or

lymphoproliferative disease

Investigate/stop therapy

Caution in pre-malignant conditions

Preventative skin care/ongoing surveillance


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


PharmacySafety with Rituximab

Delay post-anti-TNF

Check immunoglobulins

Re-treat on clinical signs

Active infection, severe immunocompromised

Screen for hepatitis (B & C)


PharmacyAbatacept


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

Increase in efficacy after first year of treatment


PharmacyTocilizumab


PharmacyTocilizumab (contd)

Recommended by SMC for combination

therapy only i.e. with MTX

ADRs e.g. liver enzymes, neutropenia,

lipids etc . . .

Place in therapy?


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 outcome due May 2010


PharmacySummary

• RA = inflammatory & destructive

• symptomatic relief

• early disease modification

Documents

Rheumatoid Arthritis