1. Southampton Biologics Review Service Dr Chris Holroyd Consultant Rheumatologist University Hospital Southampton NHS FT

2. Teaching hospital and tertiary referral centre Foundation Trust since October 2011 Rheumatology department serves a population of approx. 800,000 2900 new referrals per year 11,800 follow-up appointments per year At time: 3 FTE consultant; 2 SpRs; 2 SHOs and 0.5 WTE clinical assistant; 5 nurse specialists.

3. Biologic use in UHS FT The treatment of inflammatory arthritis has been revolutionized by the introduction of biological therapies A large body of clinical research and NICE guidance supports the use of these therapies NICE recommends that a specialist reviews all patients starting biological therapies at 3 months and 6 monthly thereafter

4. Biologic use in UHS FT ~2000 patients with RA under review Biologics to 569 patients with inflammatory arthritis. Biologics spend of ~£6 million Despite local funding supporting the provision of these drugs, no infrastructure costs were provided to ensure NICE compliance and service delivery UHS also had a low number of rheumatology consultants compared to national average (3 FTE) lowest 5% of acute trusts for Rheumatology consultants per head of population) The pressure from workload has made it difficult to review patients on biological therapies adequately

5. Challenges Insufficient follow-up frequency, lack of continuity, lack of consultant follow-up ?NICE compliant – eligibility and response How many patients on which drug and for which condition Inadequate patient education Excess biologic waste; delays in prescription changes reaching delivery company Unable to feedback to commissioners re: biologics use Inaccurate tallying of biologic cost to commissioners billing

6. Solution - Biologics Review Service 4 key objectives, in line with NHS Health and Social Care Bill 2011 Prioritise patients (quality, outcome,satisfaction) Increase efficiency (QIPP initiative) Deliver outcome measures Facilitate and promote research

7. Prioritise patients Ensure we provide highest level of care Continuity of care Extended appointment time for patient education Clinical assessment of disease activity and related co- morbidities Musculoskeletal ultrasound Patient satisfaction

8. Increase efficiency Part of UHS QIPP agenda “streamlined one-stop shop” with a dedicated nurse specialist and consultant provide single point of contact Regular review allows rapid identification of non-responders and discontinuation of inappropriate or ineffective treatments Increased patient education to reduce out-patient DNA Pharmacy measures to reduce waste SHIPP guidance (Hampshire biologic pathway)

9. Deliver outcome measures DAS/ BASDAI/ pSARC / USS/ HAQ assessment Unique database of biologics patients Regular feedback to commissioners (quarterly reports)

10. Research Identify eligible patients for clinical trials –Commercial clinical trials –Other CLRN research studies Develop novel real world research projects –Biologic dose reduction –Biosimilars

11. Process 2010 - Issues and concerns raised with commissioners Commissioners and providers worked very closely together from the beginning to agree investment terms from outset. Early collaboration with commissioners has been highlighted as one of the strengths of service Initially funding agreed for a dedicated biologics pharmacist Business case assembled for a dedicated biologics review service (2011) Funding annually required for: –Consultant (6 PAs) –USS machine: (annualised over 5 years) –Ultrasound technician (0.4 FTE) –Biologics pharmacist (0.6 FTE) –Nursing and admin support~ £239K PA Projected savings of £543,989 annually Savings based on 77 (~20%) patients with inadequately controlled disease switching to more effective and cheaper biologic (Rituximab), 23 (~5%) patients stopping biologic therapy

12. Process Business case agreed by commissioners Higher tariff per patient attendance £237 in view of extended appointment time (including USS appointment); covers Trust costs Cost to commissioners: 239k (BRC) – 112k (routine F-up) = 127k pa Gain share: agree to share net savings (544-127= 417k pa) between trust and commissioners; 50/50 for first 3 years – then 100% of savings to commissioners Regular feedback to commissioners

13. Process Dedicated consultant rheumatologist (6 PAs) was appointed to lead the service alongside a dedicated biologics specialist nurse and trained msk ultrasonographer All patients receiving biologic therapies for inflammatory arthritis were identified and moved across dedicated biologics review clinics Estimate: 24 patients per week (504 patients every 6 months (457 follow-ups + -20 new starters (based on 42 weeks clinical activity). 4 clinics (each with 6 patients) 40 minutes with consultant; 20 minutes USS Biologics review service commenced Jan 2012 Jan 2013 – clinic appointment reduced to 30mins (3 BIO clinic of 8 patients plus 1 parallel nurse clinic of 6 patients)

14. Other process changes Improved patient education to support adherence and understanding Patient information leaflet: stock control, storage, faulty devices, communication with homecare company Patient contract: signed to acknowledge their responsibility i.e. attending review clinic, blood tests, correct storage and stock control of biologic

15. Process Electronic home care biologic prescription within UHS information system. Supports accurate reconciliation of invoices and billing of PCTs. Homecare biologic spend captured – aids budget planning. Revised home care service in line with Hackett report: 4 weeks delivery, telephone stock checks, increased patient training, timely communication of prescription changes from clinic to home care company (same day). Patient accounts closed on day treatment stopped to prevent deliveries not required. Reduced waste.

16. Patient attends biologic clinic appointment MSK USS by dedicated biologics clinic ultrasonographer (20 mins) Review by consultant rheumatologist and dedicated biologics specialist nurse (30 mins) Assessment of disease activity (DAS / pSARC BASDAI/ HAQ) Assesment of CV risk Asessment of fracture risk Education Notes searched from diagnosis onwards and details entered into database Patient responding to biologic therapy in accordance with NICE Patient response to biologic in inadequate ?clinical trial Switch/ stop biologic (+/- non-bio DMARD changes) RV 3 months Continue with biologic (+/- non-bio) ?biologic dose reduction DMARD changes RV 6 months

17. Specialist Nurse Role Providing continuity of care - named point of contact for patients, telephone support between appointments. All bioloigcs helpline calls dealt with by single nurse Education- focusing on infection, vaccines, surgery, home delivery, storage of drugs, wastage and lifestyle advice e.g. smoking Managing patient expectations Smoking cessation - 24% of patients asked still smoke Close links with clinical trial nurses

18. Database APEX database (within trust IT system) All patients notes searched from diagnosis onwards and entered into database (earliest date of diagnosis Jan 1962) Separate entry for each clinic attendance Easily auditable Several built-in programmes to generate reports for commissioners Provided “free” by trust. No admin/ support fees Single point of access with IT

19. Southampton Biologics Review Clinic Commissioner’ Report Number of patients on a biologic therapy: ….of which __ (%) have a completed NHS number __ (%) have the date of birth recorded __ (%) have the registered GP recorded __ (%) have a diagnosis of Rheumatoid Arthritis (RA), AS or PsA __ (%) of the patients with RA have a pre-therapy DAS score recorded __ (%) of the patients with RA and a pre-therapy DAS scores meet NICE eligibility criteria. __ (%) of the patients with AS have a pre-therapy BASDAI score recorded __ (%) of the patients with AS and a pre-therapy BASDAI meet NICE eligibility criteria

20. __ (%) of the patients with RA have a current DAS score recorded __ (%) of the patients with AS have a current BASDAI score recorded __ (%) of patients with AS or RA have a current DAS or BASDAI score recorded with a date __ (%) have their current drug, dose and frequency all recorded __ (%) have no missing data in ANY of the following fields: –NHS Number, Date of birth, Registered GP, Current biologic including dose and frequency Recently __(%) of patients on a reduced dose/ frequency biologic

21. Outcome data 569 patients receiving biologics reviewed Mean space between scheduled appointments is 4.6 months All RA patients attending underwent DAS assessment (if recent ESR/ CRP available) All patients attending completed HAQ assessment Self-reported employment status completed for all patients Smoking history obtained All patients with RA and pSA underwent MSK ultrasound and grading of synovitis

22. Outcome data 39% no change in biologic 28% switched biological therapy 15% stopped biological therapy 18% maintained on reduced dose / frequency of biological therapy

23. Patient satisfaction survey results All participants agree they are treated with respect and dignity by all staff at the clinic. 93% find it beneficial to see the same Dr and nurse at clinic visits. 75% found the ultrasound service beneficial. 90% find the extra time in clinics valuable. 87% were satisfied that their questions were answered when they phoned the advice line. 83% of patients agree that they have been able to get help quickly when their disease flares. 100% agree that the clinic provides them with information about their condition and treatment. 100% of patients are satisfied with the care that they receive at the clinic. 97% feel confident in understanding and managing their disease, as a result of attending the clinic. Only 26% of patients were interested in attending relevant education sessions and a local patient group. ‘ A fantastic service offering lots of support and advice.’ ‘ Fantastic specialist nurses.’ ‘ Specialist R.A physio would be invaluable.’ ‘ Excellent Service. Thank – you.’

24. Financial Benefits Commissioners: Drugs savings £747k / 16% Increase in new clinic activity £239k Reduction in follow up activity £112k Net saving £620k –310k trust –310k commissioners

25. Research Novel real-world data presented nationally/ internationally –Holroyd C et al. A strategy for selecting individuals with RA for reduction of anti-TNF therapy using combined clinical and ultrasound assessment. Arthritis Rheum 2013; 65(Suppl): S339 –Marks J, Holroyd C et al. Characteristics of rheumatoid arthritis patients able to reduce anti-TNF therapy using a strategy combining clinical and ultrasound assessment. Rheumatology 2014; 53(Suppl 1): i94 –Marks J, Holroyd C et al. Does combined clinical and ultrasound assessment allow selection of individuals with rheumatoid arthritis for sustained reduction of anti-TNF therapy? Arth Care Res 2015;67:746-753 –Fong W, Holroyd C et al. Effectiveness of dose reduction of TNF inhibitors in maintaining low disease activity in severe ankylosing spondylitis. Ann Rheum Dis 2015;74(Suppl2): 285 –Fong W, Holroyd C et al. Effectiveness of dose reduction of TNF inhibitors in maintaining low disease activity in severe psoriatic arthritis. Ann Rheum Dis2015;74(Suppl2): 351 –Serhal L, Holroyd C et al. Are there negative effects on disease activity and function associated with failed anti-TNF dose reduction strategies for RA patients? EULAR 2016 –Wallis D, Holroyd C et al. Dose reduction of biological therapies in rheumatoid arthritis - the patient's perspective. BSR 2016 –Holroyd C, Parker L et al. Switching to biosimilar infliximab: real world data from the Southampton biological therapies review service. BSR 2016

26. Research Recruitment into NIHR CRN adopted studies has increased –ALIGN (Multi-country cross-sectional study to determine patient specific and general beliefs towards medication and their treatment adherence to selected systemic therapies in 6 inflammatory diseases) –ASCORE (Long term experience with abatacept sc in routine clinical practice) –CIMAX (A Non-interventional study to assess the effectiveness of certolizumab in patients with axial spondyloarthritis in daily practice) –R4RA (A Randomised, open labelled study in anti-TNF inadequate responders to investigate the mechanisms for Response – resistance to Rituximab versus Tocilizumab in RA)

27. Next steps Service has been audited yearly AS/ PsA/ RA – separated into dedicated clinics to improve outcome data collection Dedicated physiotherapist appointed RA biologics patient forum established to explore patient views on biologics Further gain share – biosimilar infliximab (50/50 saving for 3 years) –Savings used to appoint permanent dedicated biologics administrator Biosimilar etanercept gain share presently in discussion

28. Thank you