Pharmacy Rheumatoid Arthritis Carole Callaghan Principal Pharmacist NHS

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Pharmacy Rheumatoid Arthritis Carole Callaghan Principal Pharmacist NHS Lothian Educational Solutions for Workforce Development

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

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. Educational Solutions for Workforce Development

Objectives Pharmacy • Describe the common signs and symptoms associated with rheumatoid arthritis. •

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. Educational Solutions for Workforce Development

Rheumatoid Arthritis Pharmacy A chronic systemic inflammatory disease, characterised by potentially deforming symmetrical polyarthritis

Rheumatoid Arthritis Pharmacy A chronic systemic inflammatory disease, characterised by potentially deforming symmetrical polyarthritis and extraarticular features. Educational Solutions for Workforce Development

Epidemiology • • Pharmacy prevalence approx. 1% in UK 3: 1 ratio of females:

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 Educational Solutions for Workforce Development

Pathogenesis • • • cause remains unknown toxic substances found in synovium destruction of

Pathogenesis • • • cause remains unknown toxic substances found in synovium destruction of joints immunological disturbances identified RA is an autoimmune disease Educational Solutions for Workforce Development Pharmacy

Pathology • disease of the synovium • inflammation due to infiltration of lymphocytes, macrophages

Pathology • disease of the synovium • inflammation due to infiltration of lymphocytes, macrophages etc • proliferation of cells results in ”pannus” formation Educational Solutions for Workforce Development Pharmacy

Pathology Educational Solutions for Workforce Development Pharmacy

Pathology Educational Solutions for Workforce Development Pharmacy

Pathology Educational Solutions for Workforce Development Pharmacy

Pathology Educational Solutions for Workforce Development Pharmacy

Symptoms Pharmacy • joint pain (usually worse on waking) • morning stiffness (can vary

Symptoms Pharmacy • joint pain (usually worse on waking) • morning stiffness (can vary in duration) • general symptoms e. g. fatigue, malaise, bone ‘ache’ Educational Solutions for Workforce Development

Signs • • • Pharmacy swelling tenderness reduced range of movement deformities (if untreated

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 Educational Solutions for Workforce Development

Signs Pharmacy Educational Solutions for Workforce Development

Signs Pharmacy Educational Solutions for Workforce Development

Joint involvement • • • hands/wrists elbows/shoulders cervical spine knees ankles/feet unpredictable pattern Educational

Joint involvement • • • hands/wrists elbows/shoulders cervical spine knees ankles/feet unpredictable pattern Educational Solutions for Workforce Development Pharmacy

Investigation • Imaging e. g. x-ray, ultrasound, MRI • FBC and ESR • Other

Investigation • Imaging e. g. x-ray, ultrasound, MRI • FBC and ESR • Other tests e. g Rh. F, anti-CCP (antibodies) Educational Solutions for Workforce Development Pharmacy

Management (1 st stage) • lifestyle – maintain where possible • multidisciplinary e. g.

Management (1 st stage) • lifestyle – maintain where possible • multidisciplinary e. g. – physiotherapy – occupational therapy – podiatry Educational Solutions for Workforce Development Pharmacy

Management (2 nd stage) • relief of symptoms Educational Solutions for Workforce Development Pharmacy

Management (2 nd stage) • relief of symptoms Educational Solutions for Workforce Development Pharmacy

NSAIDs Pharmacy • more effective than simple analgesics • variation in response • balance

NSAIDs Pharmacy • more effective than simple analgesics • variation in response • balance efficacy • and toxicity Educational Solutions for Workforce Development

NSAID toxicity • related to dose and duration of therapy – GI – renal

NSAID toxicity • related to dose and duration of therapy – GI – renal and cardiovascular – elderly more at risk Educational Solutions for Workforce Development Pharmacy

GI toxicity • well documented in literature • identifiable risk factors e. g. age,

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 Educational Solutions for Workforce Development Pharmacy

NSAID summary • use lowest dose compatible with symptom relief • use gastroprotection in

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 Educational Solutions for Workforce Development Pharmacy

COX-2 Inhibitors Pharmacy • selectively block COX-2 isoenzyme • provide pain relief (as efficacious

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? ? Educational Solutions for Workforce Development

Management (3 rd stage) Pharmacy • long-term suppressive drug therapy with disease modifying anti-rheumatic

Management (3 rd stage) Pharmacy • long-term suppressive drug therapy with disease modifying anti-rheumatic drugs (DMARDs) Educational Solutions for Workforce Development

Early DMARD • stabilise joint function as early as possible = better outcome •

Early DMARD • stabilise joint function as early as possible = better outcome • greater awareness of NSAID toxicity • DMARDs slow disease progression Educational Solutions for Workforce Development Pharmacy

DMARDs Pharmacy • efficacy. vs. toxicity – methotrexate and sulfasalazine have the best efficacy:

DMARDs Pharmacy • efficacy. vs. toxicity – methotrexate and sulfasalazine have the best efficacy: toxicity ratio in metaanalyses • Increased use of combination therapy – TICORA, COBRA, Be. ST. – better than sequential monotherapy Educational Solutions for Workforce Development

DMARDs (cont) • DAS 28 (Disease Activity Score) -swollen joints -tender joints -ESR -patient’s

DMARDs (cont) • DAS 28 (Disease Activity Score) -swollen joints -tender joints -ESR -patient’s general health score • Monitoring -FBC -LFTs -U&Es -BP -urinalysis Educational Solutions for Workforce Development Pharmacy

Systemic corticosteroids • not recommended for routine use • if necessary, use lowest dose,

Systemic corticosteroids • not recommended for routine use • if necessary, use lowest dose, shortest time • monitor due to side effect profile Educational Solutions for Workforce Development Pharmacy

Intra-articular corticosteroids Pharmacy • “target” joint i. e. one or two large joints affected,

Intra-articular corticosteroids Pharmacy • “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 Educational Solutions for Workforce Development

TNF a - Mode of Action Activated Macrophage s. T NF R Pharmacy Target

TNF a - Mode of Action Activated Macrophage s. T NF R Pharmacy Target Cell Signal TNF Educational Solutions for Workforce Development

Anti-TNF Biologics - Mode of Action Activated Macrophage Pharmacy Target Cell TNFR s. T

Anti-TNF Biologics - Mode of Action Activated Macrophage Pharmacy Target Cell TNFR s. T NF R Signal TNF Educational Solutions for Workforce Development

TNF a Pharmacy Three agents currently licensed in UK and SMC approved: infliximab (human

TNF a Pharmacy Three agents currently licensed in UK and SMC approved: infliximab (human antichimeric antibody) etanercept (fusion protein) adalimumab (fully humanised monocloncal antibody) Educational Solutions for Workforce Development

Effects of Blocking TNFa Immunology RF, T cell function restored Inflammation Cytokine production in

Effects of Blocking TNFa Immunology RF, T cell function restored Inflammation Cytokine production in joints (IL 1, IL 6, TNF) Angiogenesis levels of angiogenesis Joint destruction damage to bone and cartilage Haematology platelets, fibrinogen, restoration of Hb Educational Solutions for Workforce Development Pharmacy

B Cell Involvement in the Pathogenesis of RA Educational Solutions for Workforce Development Pharmacy

B Cell Involvement in the Pathogenesis of RA Educational Solutions for Workforce Development Pharmacy

Biologic Pathways Educational Solutions for Workforce Development Pharmacy

Biologic Pathways Educational Solutions for Workforce Development Pharmacy

Nomenclature -ximab Chimeric antibody -zumab Humanised antibody -umab Human antibody -cept Fusion protein Educational

Nomenclature -ximab Chimeric antibody -zumab Humanised antibody -umab Human antibody -cept Fusion protein Educational Solutions for Workforce Development Pharmacy

Immunogenecity Educational Solutions for Workforce Development Pharmacy

Immunogenecity Educational Solutions for Workforce Development Pharmacy

Eligibility Criteria for Biologic Therapy (BSR) DAS 28 >5. 1 At least 2 previous

Eligibility Criteria for Biologic Therapy (BSR) DAS 28 >5. 1 At least 2 previous DMARDs Adequate response at 3 months 3 -monthly monitoring Educational Solutions for Workforce Development Pharmacy

Infection Pharmacy Do not initiate in presence of serious active infection or in patients

Infection Pharmacy Do not initiate in presence of serious active infection or in patients at high risk Discontinue in presence of serious infection Educational Solutions for Workforce Development

Tuberculosis Screen for TB Active TB needs to adequately treated Prophylactic anti-TB therapy for

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 Educational Solutions for Workforce Development Pharmacy

Other Infections Listeria/salmonella Varicella HBV/HCV HIV Educational Solutions for Workforce Development Pharmacy

Other Infections Listeria/salmonella Varicella HBV/HCV HIV Educational Solutions for Workforce Development Pharmacy

Vaccination Data limited Influenza and pnuemococcal recommended (many also on MTX) Hep B Educational

Vaccination Data limited Influenza and pnuemococcal recommended (many also on MTX) Hep B Educational Solutions for Workforce Development Pharmacy

Malignancy No increased risk of solid tumours or lymphoproliferative disease Investigate/stop therapy Caution in

Malignancy No increased risk of solid tumours or lymphoproliferative disease Investigate/stop therapy Caution in pre-malignant conditions Preventative skin care/ongoing surveillance Educational Solutions for Workforce Development Pharmacy

Rituximab Pharmacy With MTX only (SMC restricted use) Inadequate response or intolerant of other

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 Educational Solutions for Workforce Development

Safety with Rituximab Delay post-anti-TNF Check immunoglobulins Re-treat on clinical signs Active infection, severe

Safety with Rituximab Delay post-anti-TNF Check immunoglobulins Re-treat on clinical signs Active infection, severe immunocompromised Screen for hepatitis (B & C) Educational Solutions for Workforce Development Pharmacy

Abatacept Educational Solutions for Workforce Development Pharmacy

Abatacept Educational Solutions for Workforce Development Pharmacy

Abatacept (contd) Selective T cell co-stimulation modulator – blocks the co-stimulatory signal required for

Abatacept (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 Educational Solutions for Workforce Development Pharmacy

Tocilizumab Educational Solutions for Workforce Development Pharmacy

Tocilizumab Educational Solutions for Workforce Development Pharmacy

Tocilizumab (contd) Recommended by SMC for combination therapy only i. e. with MTX ADRs

Tocilizumab (contd) Recommended by SMC for combination therapy only i. e. with MTX ADRs e. g. liver enzymes, neutropenia, lipids etc. . . Place in therapy? Educational Solutions for Workforce Development Pharmacy

Certolizumab Nanomolecule comprising a humanised antibody fragment against TNF alpha with a polyethylene glycol

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 (ACR 20) compared with placebo and methotrexate SMC outcome due May 2010 Educational Solutions for Workforce Development Pharmacy

Summary • RA = inflammatory & destructive • symptomatic relief • early disease modification

Summary • RA = inflammatory & destructive • symptomatic relief • early disease modification Educational Solutions for Workforce Development Pharmacy