Core course lecture - Rheumatoid Arthritis

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Core course lecture - Rheumatoid Arthritis
29 Jan 2008
Carole Callaghan

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Core course lecture - Rheumatoid Arthritis

  1. 1. Rheumatoid Arthritis Carole Callaghan Principal Pharmacist NHS Lothian
  2. 2. Aim <ul><li>To update pharmacists on the current </li></ul><ul><li>management of rheumatoid arthritis and </li></ul><ul><li>explore ways to implement </li></ul><ul><li>pharmaceutical care for this patient group </li></ul><ul><li>as part of normal working practice. </li></ul>
  3. 3. Objectives <ul><li>Describe the common signs and symptoms associated with rheumatoid arthritis. </li></ul><ul><li>Define the current therapeutic management for both the alleviation of symptoms and for modifying disease progression in rheumatoid arthritis. </li></ul><ul><li>Identify pharmaceutical care issues and appropriate management solutions when responding to symptoms in patient scenarios. </li></ul><ul><li>Explore how to implement the principles of a pharmaceutical care needs assessment tool in practice. </li></ul>
  4. 4. Rheumatoid Arthritis <ul><li>A chronic systemic inflammatory disease, characterised by potentially deforming symmetrical polyarthritis and extra-articular features. </li></ul>
  5. 5. Epidemiology <ul><li>prevalence approx. 1% in UK </li></ul><ul><li>3:1 ratio of females:males affected </li></ul><ul><li>peak onset 40 and 50 years of age </li></ul><ul><li>genetic, environmental and infective factors involved in disease development </li></ul>
  6. 6. Pathogenesis <ul><li>cause remains unknown </li></ul><ul><li>toxic substances found in synovium </li></ul><ul><li>destruction of joints </li></ul><ul><li>immunological disturbances identified </li></ul><ul><li>RA is an autoimmune disease </li></ul>
  7. 7. Pathology <ul><li>disease of the synovium </li></ul><ul><li>inflammation due to infiltration of lymphocytes, macrophages etc </li></ul><ul><li>proliferation of cells results in ”pannus” formation </li></ul>
  8. 8. Pathology
  9. 9. Pathology
  10. 10. Symptoms <ul><li>joint pain (usually worse on waking) </li></ul><ul><li>morning stiffness (can vary in duration) </li></ul><ul><li>general symptoms e.g. fatigue, malaise, bone ‘ache’ </li></ul>
  11. 11. Signs <ul><li>swelling </li></ul><ul><li>tenderness </li></ul><ul><li>reduced range of movement </li></ul><ul><li>deformities (if untreated over long-term) </li></ul><ul><li>extra-articular features e.g. nodules, anaemia of chronic disease, pleural effusion </li></ul>
  12. 12. Signs
  13. 13. Joint involvement <ul><li>hands/wrists </li></ul><ul><li>elbows/shoulders </li></ul><ul><li>cervical spine </li></ul><ul><li>knees </li></ul><ul><li>ankles/feet </li></ul><ul><li>unpredictable pattern </li></ul>
  14. 14. Investigation <ul><li>Imaging e.g. x-ray, ultrasound, MRI </li></ul><ul><li>FBC and ESR </li></ul><ul><li>Other tests e.g RhF, anti-CCP (antibodies) </li></ul>
  15. 15. Management (1st stage) <ul><li>lifestyle – maintain where possible </li></ul><ul><li>multidisciplinary e.g. </li></ul><ul><ul><li>physiotherapy </li></ul></ul><ul><ul><li>occupational therapy </li></ul></ul><ul><ul><li>podiatry </li></ul></ul>
  16. 16. Management (2nd stage) <ul><li>relief of symptoms </li></ul>
  17. 17. NSAIDs <ul><li>more effective than simple analgesics </li></ul><ul><li>variation in response </li></ul><ul><li>balance efficacy </li></ul><ul><li>and toxicity </li></ul>
  18. 18. NSAID toxicity <ul><li>related to dose and duration of therapy </li></ul><ul><ul><li>GI </li></ul></ul><ul><ul><li>renal and cardiovascular </li></ul></ul><ul><ul><li>elderly more at risk </li></ul></ul>
  19. 19. GI toxicity <ul><li>well documented in literature </li></ul><ul><li>identifiable risk factors e.g. age, previous history, other medication (steroids, warfarin), alcohol </li></ul><ul><li>improved use secondary to identifying those at risk and using gastroprotection </li></ul>
  20. 20. NSAID summary <ul><li>use lowest dose compatible with symptom relief </li></ul><ul><li>use gastroprotection in “at risk” patient </li></ul><ul><li>reduce and, if possible, withdraw when good response from DMARD </li></ul>
  21. 21. COX-2 Inhibitors <ul><li>selectively block COX-2 isoenzyme </li></ul><ul><li>provide pain relief (as efficacious as NSAIDs) </li></ul><ul><li>less GI bleeding than NSAIDs (less significant GI symptoms remain e.g. dyspepsia) </li></ul><ul><li>CV risk?? </li></ul>
  22. 22. Management (3rd stage) <ul><li>long-term suppressive drug therapy with disease modifying anti-rheumatic drugs (DMARDs) </li></ul>
  23. 23. Early DMARD <ul><li>stabilise joint function as early as possible = better outcome </li></ul><ul><li>greater awareness of NSAID toxicity </li></ul><ul><li>DMARDs slow disease progression </li></ul>
  24. 24. DMARDs <ul><li>efficacy .vs. toxicity </li></ul><ul><ul><li>methotrexate and sulfasalazine have the best efficacy:toxicity ratio in meta-analyses </li></ul></ul><ul><li>Increased use of combination therapy – TICORA, COBRA, BeST. </li></ul><ul><ul><li>better than sequential monotherapy </li></ul></ul>
  25. 25. DMARDs (cont) <ul><li>DAS28 (Disease Activity Score) </li></ul><ul><li>- swollen joints </li></ul><ul><li>-tender joints </li></ul><ul><li>-ESR </li></ul><ul><li>-patient’s general health score </li></ul><ul><li>Monitoring </li></ul><ul><li>-FBC </li></ul><ul><li>-LFTs </li></ul><ul><li>-U&Es </li></ul><ul><li>-BP </li></ul><ul><li>-urinalysis </li></ul>
  26. 26. Systemic corticosteroids <ul><li>not recommended for routine use </li></ul><ul><li>if necessary, use lowest dose, shortest time </li></ul><ul><li>monitor due to side effect profile </li></ul>
  27. 27. Intra-articular corticosteroids <ul><li>“ target” joint i.e. one or two large joints affected, can avoid systemic steroid </li></ul><ul><li>maximum number per joint/time – but no evidence for this theory </li></ul><ul><li>evidence lacking for this practice, </li></ul><ul><li>but patients report benefit </li></ul>
  28. 28. TNF  -  Mode of Action Activated Macrophage TNF Target Cell Signal sTNFR
  29. 29. Anti-TNF Biologics - Mode of Action Activated Activated Macrophage Target Target Cell Cell Signal Signal sTNFR sTNFR TNF TNF TNFR TNFR
  30. 30. TNF  <ul><li>Three agents currently licensed in UK and </li></ul><ul><li>SMC approved: </li></ul><ul><li>infliximab (human antichimeric antibody) </li></ul><ul><li>etanercept (fusion protein) </li></ul><ul><li>adalimumab (fully humanised monocloncal antibody) </li></ul>
  31. 31. Effects of Blocking TNF  <ul><li>Immunology </li></ul><ul><ul><li> RF, T cell function restored </li></ul></ul><ul><li>Inflammation </li></ul><ul><ul><li> Cytokine production in joints (IL1, IL6, TNF) </li></ul></ul><ul><li>Angiogenesis </li></ul><ul><ul><li> levels of angiogenesis </li></ul></ul><ul><li>Joint destruction </li></ul><ul><ul><li> damage to bone and cartilage </li></ul></ul><ul><li>Haematology </li></ul><ul><ul><li> platelets, fibrinogen, restoration of Hb </li></ul></ul>
  32. 32. B Cell Involvement in the Pathogenesis of RA
  33. 33. Biologic Pathways
  34. 34. Nomenclature <ul><li>-ximab Chimeric antibody </li></ul><ul><li>-zumab Humanised antibody </li></ul><ul><li>-umab Human antibody </li></ul><ul><li>-cept Fusion protein </li></ul>
  35. 35. Immunogenecity
  36. 36. Eligibility Criteria for Biologic Therapy (BSR) <ul><li>DAS28 >5.1 </li></ul><ul><li>At least 2 previous DMARDs </li></ul><ul><li>Adequate response at 3 months </li></ul><ul><li>3-monthly monitoring </li></ul>
  37. 37. Infection <ul><li>Do not initiate in presence of serious </li></ul><ul><li>active infection or in patients at high risk </li></ul><ul><li>Discontinue in presence of serious </li></ul><ul><li>infection </li></ul>
  38. 38. Tuberculosis <ul><li>Screen for TB </li></ul><ul><li>Active TB needs to adequately treated </li></ul><ul><li>Prophylactic anti-TB therapy for potential latent </li></ul><ul><li>disease </li></ul><ul><li>Monitor during/after biologic; treat if required </li></ul>
  39. 39. Other Infections <ul><li>Listeria/salmonella </li></ul><ul><li>Varicella </li></ul><ul><li>HBV/HCV </li></ul><ul><li>HIV </li></ul>
  40. 40. Vaccination <ul><li>Data limited </li></ul><ul><li>Influenza and pnuemococcal </li></ul><ul><li>recommended (many also on MTX) </li></ul><ul><li>Hep B </li></ul>
  41. 41. Malignancy <ul><li>No increased risk of solid tumours or </li></ul><ul><li>lymphoproliferative disease </li></ul><ul><li>Investigate/stop therapy </li></ul><ul><li>Caution in pre-malignant conditions </li></ul><ul><li>Preventative skin care/ongoing surveillance </li></ul>
  42. 42. Rituximab <ul><li>With MTX only (SMC restricted use) </li></ul><ul><li>Inadequate response or intolerant of other </li></ul><ul><li>DMARDs, including at least one anti-TNF </li></ul><ul><li>By specialists in accordance with criteria </li></ul>
  43. 43. Safety with Rituximab <ul><li>Delay post-anti-TNF </li></ul><ul><li>Check immunoglobulins </li></ul><ul><li>Re-treat on clinical signs </li></ul><ul><li>Active infection, severe immunocompromised </li></ul><ul><li>Screen for hepatitis (B & C) </li></ul>
  44. 44. Abatacept
  45. 45. Abatacept (contd) <ul><li>Selective T cell co-stimulation modulator – </li></ul><ul><li>blocks the co-stimulatory signal required for full </li></ul><ul><li>T cell activation </li></ul><ul><li>Not recommended by SMC and reserved for </li></ul><ul><li>refractory disease. However, this advise superseded by </li></ul><ul><li>NICE MTA 195 and can now be used in anti-TNF or </li></ul><ul><li>rituximab failure/intolerant </li></ul><ul><li>Increase in efficacy after first year of treatment </li></ul>
  46. 46. Tocilizumab
  47. 47. Tocilizumab (contd) <ul><li>Recommended by SMC for combination </li></ul><ul><li>therapy only i.e. with MTX </li></ul><ul><li>ADRs e.g. liver enzymes, neutropenia, </li></ul><ul><li>lipids etc . . . </li></ul><ul><li>Place in therapy? </li></ul>
  48. 48. Certolizumab <ul><li>Nanomolecule comprising a humanised </li></ul><ul><li>antibody fragment against TNF alpha with </li></ul><ul><li>a polyethylene glycol tail - designed </li></ul><ul><li>to increase bioavailability </li></ul><ul><li>RCTs show rapid improvement in disease </li></ul><ul><li>activity (ACR20) compared with placebo </li></ul><ul><li>and methotrexate </li></ul><ul><li>SMC approved (in conjunction with patient access </li></ul><ul><li>scheme) </li></ul>
  49. 49. Summary <ul><li>RA = inflammatory & destructive </li></ul><ul><li>symptomatic relief </li></ul><ul><li>early disease modification </li></ul>

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