1. Modern Therapeutics in Rheumatic Diseases Alistair Duncan (Clinical Pharmacist) Lynn Sinclair (Rheumatology Nurse) The Robert Gordon University Non Medical Prescribing Conference 2014

2. Developments in Therapeutics for.... Rheumatoid Arthritis Psoriatic Arthritis Ankylosing Spondylitis Biologics have revolutionised treatment and outlook for those with inflammatory joint diseases

3. Rheumatoid Arthritis Emphasis is now on: –Early diagnosis –Early (and aggressive) treatment Methotrexate is the GOLD STANDARD treatment

4. Goals of Treatment Reduce pain and inflammation Preserve function Maintain employment Remission / Cure Reduce cardiovascular risk

6. Symptomatic Control Analgesia –As per WHO analgesic ladder NSAIDs –Take into account co-morbidities –COX 1 vs COX 2 selectivity –Cardiovascular and GI side effects Steroids – i.m. / i.a. / oral

8. Traditional DMARDs Disease Modifying Anti-Rheumatic Drugs Methotrexate Sulfasalazine Hydroxychloroquine Leflunomide Penicillamine Ciclosporin Gold (injection) Azathioprine Cyclophosphamide Chlorambucil Prednisolone

9. A: Placebo ! B: Auranofin C: Antimalarial D: Azathioprine E: Methotrexate F: Sulfasalazine G: Penicillamine H: IM Gold

10. Methotrexate First used in 1947 for childhood leukaemia Probably the most effective DMARD Convenient ONCE weekly dosing ??? Faster onset of action (6 weeks to 3 months) –(compared to other DMARDs) Mode of action - unclear!! Remember – Folic acid

11. Side Effects Nausea, stomatitis Haematological toxicity Hepatic toxicity –LFTs, cirrhosis, hepatic fibrosis Pulmonary toxicity –pneumonitis Teratogenic (ova and sperm)

13. Responsibility of the Consultant Responsibility of the GP + monitoring schedule Patient specific information

14. What to do if…? General Responsibilities Prescribing Information

16. A Patient’s Story

17. Methotrexate Safety 2.5mg tablets and 10mg tablets now as different shapes NHSG policy is to always prescribe 2.5mg tablets Ensure patient understands dose in terms of mg and number of tablets Avoid use of “as directed” Remove prescriptions from repeat piles Ensure regular monitoring

18. Methotrexate Prescribing Points Ensure folic acid is prescribed Avoid Trimethoprim (+ Co-trimoxazole) Refer unexplained breathlessness/cough Caution alcohol intake Ensure adequate contraception Avoid live vaccines Follow shared care protocol

19. How to measure Rheumatoid Arthritis? 28 Joint Count

20. DAS (28) Score Swollen and Tender Joint Count ESR Global health assessment by patient DAS28 = 0.56 x sqrt(tender28) + 0.28 x sqrt(swollen28) + 0.70 x ln(ESR) + 0.014 x GH

21. DAS in Practice “An objective method for measuring disease activity”“An objective method for measuring disease activity” >5.1 = Active disease>5.1 = Active disease <3.2 = low disease activity<3.2 = low disease activity <2.6 = Remission<2.6 = Remission

22. Health Assessment Questionnaire Dress yourself including tying shoe laces and doing buttons Shampoo your hair Stand up from an armless straight chair Get in and out of bed Cut your meat Lift a full cup or glass to your mouth Walk outdoors on flat ground

23. Aids or devices that you may use Cane Crutches Walking frame Built up chair

24. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single- blind randomised controlled trial Catriona Grigor, MBChB, Hilary Capell, MD, Anne Stirling, RGN, Alex D McMahon, PhD, Peter Lock, MSc, Ramsay Vallance, FRCR, Wilma Kincaid and Duncan Porter, MBChB The Lancet Volume 364, Issue 9430, Pages 263-269Volume 364, Issue 9430, Pages 263-269 (July 2004) DOI: 10.1016/S0140-6736(04)16676-2 Copyright © 2004 Elsevier Ltd Terms and ConditionsTerms and Conditions

25. TICORA Tight Control for Rheumatoid Arthritis Intensive out-patient management of RA vs Routine Care “Treat to target” If DAS > 2.4, = step up in treatment Joints injected at monthly visits if necessary.

26. Figure 3 Source: The Lancet 2004; 364:263-269 (DOI:10.1016/S0140-6736(04)16676-2)The Lancet 2004; 364:263-269 Terms and Conditions

27. Treat to Target

28. Traditional DMARDs Disease Modifying Anti-Rheumatic Drugs Methotrexate Sulfasalazine Hydroxychloroquine Leflunomide Penicillamine Ciclosporin Gold (injection) Azathioprine Cyclophosphamide Chlorambucil Prednisolone

29. Biologics** Target pro-inflammatory cytokines –Tumour necrosis factor (TNF) alpha –Interleukin 6 –Interleukin 1 –Interleukin 12/23 (Ustekinumab for Psoriatic arthritis) Other immune pathways –B Cells –T Cells **All co-prescribed with MTX where possible

30. Eligibility for Biologics (SMC) Active disease (DAS > 5.1) –On 2 occasions, 1 month apart Adequate therapeutic trial of at least 2 DMARDs (inc methotrexate)

31. Treat to Target - Next Steps

32. The nurses role in assessing patients prior to commencing Anti-TNF therapy

33. Medical Requirements Bloods checked for Hepatitis B + C core Antibodies Recent chest x-ray No history of TB or MS No history of cancer Patient is not awaiting any surgical/medical/dental procedures

34. Consultant referral letter Ensure patient does not require to be TB screened Varicella Does patient meet the DAS requirement to commence Biologic (>5.1) What medication is the patient currently using for arthritis?

35. Patient safe to commence Anti-TNF When all investigations are completed and the patient is safe to proceed with the nurses assessment they will attend the department to have a repeat disease activity assessment (DAS) If patient has had recent steroids this may reflect on the actual score

36. The nurses role is then to assess the patients joints for any tenderness or swelling. ESR is obtained and recorded. Health assessment questionnaire filled in by patient and results recorded. Pain score, early morning stiffness and patients global assessed. All scores are entered into a DAS calculator

37. Patient meets the criteria to commence treatment. Education provided on the chosen drug Injection demonstrated to patient –opportunity to familiarise themselves with the injection device by using demonstration syringes Patient registered with Homecare company –Injections delivered to patients home –Homecare nurse to supervise patient doing first injection. Nurse review at 3 months - DAS recorded. Nurses review again after 3 months, then 6 monthly thereafter.

38. Patient X Etanercept Patient currently has rheumatoid arthritis and medical staff would like him assessed for possibility of commencing anti tnf therapy DAS prior to any treatment 7.64 DAS 3 months after commencing treatment 4.02 DAS 6 months after commencing treatment 2.16

39. Anti –TNF alpha Certolizumab – fortnightly s/c inj. Etanercept – weekly s/c inj. Adalimumab – fornightly s/c inj. Infliximab – 8 weekly iv infusion Golimumab – monthly s/c inj. Typically (£9 - 10k per patient per year) S/C treatments via Homecare Company

40. TNFα and it’s Receptor

41. Recombinant TNFα Soluble Receptor

42. Monoclonal antibody against TNFα

43. Adverse Effects of TNF Inhibitors Serious Infections –TB –Skin and soft tissue –Blood borne viruses Malignancy –? Lymphoma –? Solid Tumors –Conflicting data Injection site reactions Infusion reactions Increased risk of cardiac failure Demeyelination

45. When to with-hold biologics? Should be discontinued in the presence of serious infections, but can be recommenced once the infection has resolved clinically. Stop biologic 3 to 5 half lives before major surgery. Should not be restarted after surgery until there is good wound healing and no evidence of infection.

46. B Cell Depletion Rituximab –2 x fixed 1g doses 14 days apart –IV infusion –Dose repeated, but not at a fixed interval

47. T Cell Co-Stimulation Modulator Abatcept –4 weekly iv infusion –Now available as weekly s/c injection Interleukin 6 Inhibitor Tocilizumab 4 weekly iv infusion Now available as weekly s/c injection

48. Remember Always consider that a patient with RA / AS / PSa may be on a drug supplied via homecare Ensure recommended monitoring is carried out. Caution in patients going for major surgery, or with concurrent infection.

49. Info Resources British Society for Rheumatology (BSR) http://www.rheumatology.org.uk European League against Rheumatism (EULAR) http://www.eular.org/ Arthritis Research http://www.arthritisresearchuk.org/ SIGN 123: Management of Early RA http://www.sign.ac.uk