Rheumatology

1. Rheumatology Dr Nicky Minaur Consultant Rheumatologist North Bristol NHS Trust

2. Talk Outline • The local Rheumatology Service • A tale of two patients – opportunities and challenges • Recording biologic treatments in primary care • CTD pathway • Patients with chronic pain • Discussion

3. Rheumatology in the Region • NBT (8 Consultants), UHB (4 Consultants), Weston (2 Consultants), Gloucester (5 Consultants) • In-patient beds for all Bristol & Weston patients on Trym Ward, Avon Orthopaedic Centre, Southmead • Number of beds is currently 9 reduced from 25 beds 10 years ago New hospital?

4. Rheumatology Team at NBT • Clinics held at Southmead, Frenchay and Cossham Hospitals (Henshaw House) • 8 Consultants, 3 SpRs, 1 ST1/2 ward doctor • Specialist Nurses • Specialist Rheumatology Physiotherapy, Occupational Therapy, Psychologist • Orthotics

5. Consultant Rheumatology Staff – all see inflammatory arthritis • Dr Peter Hollingworth • SMD- medicolegal • Dr Val Kyle • FHY, CSSHM- PMR/GCA, vasculitis • Dr Paul Creamer (Clinical Lead) • SMD, FHY, CSSHM- clinical research, ankylosing spondylitis, gout • Dr Sam Patel (Rheumatology/General Medicine) • FHY- MAU, Behçet’s syndrome, vasculitis

6. Consultant Rheumatology Staff (contd) • Dr Nicky Minaur • SMD, CSSHM- modernisation, transition clinic for JIA • Prof Jon Tobias (previously UHB) • SMD- academic, osteoporosis, metabolic bone disease • Dr Emma Clark (Senior Lecturer) • SMD- academic, osteoporosis, hypermobility syndrome • Dr Harsha Gunawardena • SMD, CSSHM- connective tissue diseases, vasculitis

7. Specialised & Combined Clinics • Specialised clinics for connective tissue diseases, osteoporosis, transition patients • Combined clinics with orthopaedics hands, upper limbs, hips, knees and feet • Combined clinics with dermatology, respiratory, neurology

8. Request • Please don’t allow patients with inflammatory joint disease or connective tissue diseases (eg scleroderma) to go to an independent treatment centre for elective orthopaedic sugery • These patients need the specialised, multidisciplinary care available at NBT

9. What’s new in Rheumatology?

10. A Tale of Two Patients • Colin, now aged 71, developed RA 21 years ago • Stopped work age 50 due to RA • IM Gold, D-Penicillamine, SSZ, steroids • R TKR

11. Patient 1 • Lost to follow-up in the 1990’s • Referred back 2005, on SSZ, active RA • MTX, escalated, switched to S/C • Assessed for anti-TNF, SOB++ on Etanercept - pulmonary fibrosis • Treated with Rituximab Feb/Mar 2009

12. Patient 2 • Jill developed RA aged 50 in 2010 • Off work with RA, also diagnosed with DM • Had been started on Prednisolone 15mg by GP before referral, CRP 92 • Seen first in June 09 • Started on MTX 15mg/wk, FA, Pred weaned • Referred Rheumatology PT, OT

13. Patient 2 • Reviewed 1 month later July 09 • August 09 - SSZ added to MTX, now off steroids and diabetes resolved • Sep 09 – DAS28 6.29 (active RA), SSZ increased • Oct 09 – RSN – DAS28 5.86 (still active RA), MTX increased to 17.5mg/wk. Mood↓

14. Patient 2 • November 09 – DAS28 5.15, MTX increased to 20mg/wk, SSZ reduced to 1g bd • Reviewed 8 weeks later, Feb 10 - DAS28 3.1 • Reviewed April 10 – DAS28 2.1 • In remission after 8 visits and 10 months

15. Colin Never worked again Very disabled RA never really controlled Comorbidities Has had 2 different biologic agents Jillian RA under control within a year Back at work No disability Diabetes gone Self-managing RA, loosing weight Differences

16. 3 or 4 monthly visits for 20 years is 60-80 visits Estimate 55 visits as lost for 2 years Major joint surgery 2 biologic agents Benefits Poor quality of life 8 visits in first 10 months Estimate annual review for next 20 years This is 28 visits Additional visits as needed In work, no disability Costs: standard vs aggressive

17. Rheumatology in 1980 • NSAIDs were 1st line • Wait for erosions before starting treatment with a second-line drug • Use of IM Gold and D-Penicillamine still common

18. Outcome of delayed, tentative treatment

19. Rheumatology in 1990’s • Start DMARD as soon as diagnosis made-don’t wait for erosions- but there was often a 9 month wait from GP referral to Rheumatology appointment • Increasing use of Methotrexate and doses creeping up to 15mg/week or higher • Combination treatment eg MTX and SSZ shown to be effective in trials, not used much in practice

20. Rheumatology in 2000’s • Methotrexate became thought of as the ‘anchor drug’ • S/C Methotrexate use increased, and doses increased- commence at 15mg/wk, max 25-30mg/wk • Leflunomide introduced 2000 • Increasing use of combination Rx- MTX, SSZ, HCQ, Prednisolone

21. Rheumatology in the 2000’s • Services changed with the NHS plan • Waiting times came down dramatically • Musculoskeletal interface services developed • Case-mix in rheumatology has changed as non-inflammatory conditions are not reviewed, and ‘simple’ conditions not seen

22. Rheumatology in 2000’s • First RCT of anti-TNF therapy in RA was published in 1999 Infliximab (Maini & Feldman) • Many others followed • NICE has approved use of • Infliximab, Etanercept (2002) • Adalimumab (2007) • Certolizumab (2010) • Rituximab (2007) • In pipeline Tocilizumab and Golimumab…….

23. ATTRACT Study 2004 MTX did not halt new erosions, especially in early RA (< 2years), but may slow their development compared to no treatment Infliximab does halt new erosions, even in early RA

24. Anti-TNF is more effective in combination with MTX In clinical practice, 70% of patients are still on Rx with anti-TNF and MTX after 1 year MTX is the comparator drug in all biologic trials now

25. Standard care in 2010 • Patient may delay more than 3 months to see GP • GP may try NSAID or 2, occasionally start steroids, arrange x-rays hands and feet, do bloods (FBC, CRP, PV, RF) • GP then refers, using Choose and Book • Seen in rheumatology 6-9 weeks later, diagnosis made • Starts MTX, review 3 months

26. Standard care in 2010 • 3 monthly reviews and MTX gradually increased, then SSZ added and/ or MTX changed to S/C injections, as necessary • After approx 2 years, if still active RA • Assessed for anti-TNF

27. Timing needs to change

28. How can we apply these tools in good time?

29. NICE Clinical Guideline 79 • Rheumatoid Arthritis: the management of rheumatoid arthritis in adults • Issued February 2009 • Guidance is aspirational and will require a major shift in the way services are delivered

30. Window of opportunity ‘Remission’ may be low disease activity, or drug-free remission. NB RA does not ‘burn out’.

31. Refer for specialist opinion any person with suspected persistent synovitis of undetermined cause. Refer urgently if any of the following apply: − the small joints of the hands or feet are affected (squeeze MCPJs and MTPJs, should not hurt) − more than one joint is affected − there has been a delay of 3 months or longer between onset of symptoms and seeking medical advice. Referral for specialist treatment (NICE CG79)

32. Do not put off referring a patient with persistent synovitis to a specialist if the bloods and x-rays are normal- these tests can be normal in early RA • If symptoms have been present already for more than 3 months, reactive arthritis is unlikely and further delay affects outcome, so refer immediately

33. Single joint pain – not NICE guidance • Should be referred to Rheumatology if inflammatory • Early morning stiffness > 30 minutes, or • Boggy swelling suggesting synovitis, or • Raised inflammatory markers eg PV/CRP • Any of these features is significant • Psoriatic arthritis often presents with a mono-arthritis- personal or FH of Psoriasis?

34. Disease modifying agents(NICE CG79) Offer a combination of disease-modifying anti-rheumatic drugs (DMARDs) in people with newly diagnosed active RA, (including methotrexate and at least one other DMARD, plus short-term glucocorticoids) as soon as possible, ideally within 3 months of the onset of persistent symptoms. Start DMARD monotherapy in people with newly diagnosed RA for whom combination DMARD therapy is not appropriate.

35. Disease modifying agents(NICE CG79) • Cautiously reduce drug doses to levels that maintain disease control in people with recent-onset RA receiving combination DMARD therapy in whom disease has been controlled ie those who have gone into remissison.

36. In people with recent-onset active RA measure: - C-reactive protein (CRP) - key components of disease activity Do this monthly until disease controlled to level agreed with the person with RA Monitoring disease (NICE CG79)

37. This implies treating to a target Disease Activity Score (DAS28)- composite outcome measure of tender joints, swollen joints, patient’s global assesment of their condition, and CRP • Please measure CRP rather than PV with monitoring bloods • Target should be agreed with the patient at the start of treatment by the rheumatologist • People’s expectations are low and they are often grateful for any reduction in symptoms

38. DAS28 • Greater than 5.1 – high disease activity, threashold currently for biologic therapy, but may come down to 3.2 • Less than 3.2 – low disease activity • Less than 2.1 - remission

39. People with RA should have access to a named member of the multidisciplinary team who is responsible for coordinating their care. The multidisciplinary team (NICE CG79)

40. Person-centred care(NICE CG79) • Explain the risks and benefits of treatment options. • Offer the chance to discuss and agree care, respecting decisions made. • Offer verbal and written information to improve understanding and counter misconceptions. • Offer opportunities to take part in existing educational activities, including self-management programmes, to people who are interested.

41. NICE - see early RA monthly until in remission, perhaps 9-12 visits over first 2 years This should translate into 70% patients in remission rather than 30%- fewer for TNF We all have clinics full of existing patients, many diagnosed and treated pre-biologic era- complicated patients! We are being asked to see all chronic disease patients less often Dilemma

42. Can we abandon all the long-standing pre-biologic patients? • No, we have a duty of care to these patients too • However, in established RA (> 2 yrs), usual review should be annual • Advice and sooner review available- telephone advice line (on handout) • Patient reps’ group view

43. Recording biologic treatments in primary care • A recent audit at NBT found patients given Rituximab did not have it recorded in the GP medication lists, as hospital prescribed • Anti-TNF side effects – risk of severe infection, reactivation of TB & Hep B, worsening cardiac failure, multiple sclerosis, SLE-syndrome, if previous solid tumour increased risk of malignancy

44. Rituximab- anti-B cell • 2 infusions given a month apart, and then re-treatment if needed- mean 9 months later • Effect on immune system long-lasting • Side effects- severe infections, reactivation of TB and Hep B, rare neurological side effects progressive multifocal leucoencephalopathy, migraine, urticaria

45. Aid to ensure these medications are recorded in primary care • We propose to add a phrase to letters from the specialist nurses when patients start treatment with anti-TNF and Rituximab • Please add this treatment to the patient’s medication list, marked hospital-prescription only • Then if another GP or speciality sees the patient, they are aware of the biologic treatment • ? Likely to happen

46. Autoimmune Connective Tissue Disease Referral Pathway Symptoms of fever, weight loss, malaise, rash, arthritis, renal insufficiency, chronic sinusitis, unilateral headache, cough and/or SOB Constitutional symptoms, rash, photosensitivity, arthralgia/arthritis, Raynaud’s, alopecia, serositis, muscle weakness, skin tightening, SOB History of recurrent miscarriages or unexplained thromboses Clinically stable? Yes Consider infection or malignancy NO Negative ANA /ANCA Pre-clinic investigations: FBC, UE, LFT, PV, CK, ANA, urine dipstick, CXR, consider ANCA No other cause identified – still consider CTD / vasculitis Rheumatology SpR Southmead via Southmead switchboard or CTD Consultant Dr. Harsha Gunawardena 0117 3232175 (secretary) & 0117 323 5289 (fax) 0117 9505050 ext: 2615 (office) Mobile via NBT switchboard Email: harsha.gunawardena@nbt.nhs.uk (Positive ANA /ANCA) Clinically stable? Yes NO Refer to Dr. Harsha Gunawardena - CTD clinic (Southmead / Cossham) via Choose and Book Directorate of Musculoskeletal Services Department of Rheumatology

47. Osteoporosis • Open access DXA if amber risk on -www.sheffield.ac.uk/FRAX • Refer complex or severe OP to Prof Tobias’ osteoporosis clinic • Rachel Lewis (rheum physio) can do lunchtime meetings for interested practices talking about the physiotherapy service for osteoporosis and hypermobility syndrome

48. Patients with widespread chronic pain- ? fibromyalgia • Handout suggesting some blood tests and conditions to consider • Coeliac disease • Hypermobility syndrome

49. Benign joint hypermobility syndrome Rheumatology physio can help with postural and core stability, or, refer rheumatology (Dr Emma Clark).

50. Thanks for listening • Any Questions or Comments? • nicola.minaur@nbt.nhs.uk