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

2. Educational Solutions for Workforce Development Pharmacy Aim 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.

3. Educational Solutions for Workforce Development Pharmacy Objectives 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.

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

5. Educational Solutions for Workforce Development Pharmacy Epidemiology 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

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

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

8. Educational Solutions for Workforce Development Pharmacy Pathology

9. Educational Solutions for Workforce Development Pharmacy Pathology

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

11. Educational Solutions for Workforce Development Pharmacy Signs swelling tenderness reduced range of movement deformities (if untreated over long-term) extra-articular features e.g. nodules, anaemia of chronic disease, pleural effusion

12. Educational Solutions for Workforce Development Pharmacy Signs

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

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

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

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

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

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

19. Educational Solutions for Workforce Development 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

20. Educational Solutions for Workforce Development 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

21. Educational Solutions for Workforce Development Pharmacy COX-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??

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

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

24. Educational Solutions for Workforce Development Pharmacy DMARDs 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

25. Educational Solutions for Workforce Development Pharmacy DMARDs (cont) DAS28 (Disease Activity Score) - swollen joints -tender joints -ESR -patient’s general health score Monitoring -FBC -LFTs -U&Es -BP -urinalysis

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

27. Educational Solutions for Workforce Development 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

28. Educational Solutions for Workforce Development Pharmacy TNF  -  Mode of Action ActivatedMacrophage TNF sTNFR

29. Educational Solutions for Workforce Development Pharmacy Anti-TNF Biologics - Mode of Action

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

31. Educational Solutions for Workforce Development Pharmacy Effects 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

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

33. Educational Solutions for Workforce Development Pharmacy Biologic Pathways

34. Educational Solutions for Workforce Development Pharmacy Nomenclature -ximabChimeric antibody -zumabHumanised antibody -umabHuman antibody -ceptFusion protein

35. Educational Solutions for Workforce Development Pharmacy Immunogenecity

36. Educational Solutions for Workforce Development Pharmacy Eligibility Criteria for Biologic Therapy (BSR) DAS28 >5.1 At least 2 previous DMARDs Adequate response at 3 months 3-monthly monitoring

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

38. Educational Solutions for Workforce Development Pharmacy 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

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

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

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

42. Educational Solutions for Workforce Development Pharmacy Rituximab 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

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

44. Educational Solutions for Workforce Development Pharmacy Abatacept

45. Educational Solutions for Workforce Development Pharmacy 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. However, this advice 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

46. Educational Solutions for Workforce Development Pharmacy Tocilizumab

47. Educational Solutions for Workforce Development 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?

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