1. BAD Biologic Interventions Register (BADBIR ) An update November 2009

2. Presentation Overview Project rationale Brief history of BADBIR Aim and study design Data collection Conclusions

3. The advent of biologic agents Has been met with: –Considerable enthusiasm from both clinicians and patients –Concerns relatively high cost potential for serious side effects –efalizumab (recently had marketing license withdrawn) –anti-TNF agents (serious infections e.g. tuberculosis, certain malignancies e.g. lymphomas, demyelinating disorders, congestive heart failure)

4. How is Potential Harm of Biologic Therapy assessed? Phase I/II– Phase III Spontaneous pharmacovigilance Observational cohorts National registers Short-term safety of biologics has been evaluated in clinical trials Some long-term safety data on anti-TNF drugs available from use in other conditions e.g. inflammatory arthritis, Crohn’s disease

5. Rationale for BADBIR Patients with severe psoriasis are likely to be obese smoke abuse alcohol have a high risk of cardio-vascular disease be exposed to different types of drugs, e.g. phototherapy Therefore, data on the safety of biologic use in other conditions cannot be directly extrapolated to psoriasis Recommendation from BAD All patients treated with biologic agents be registered with BADBIR

6. Brief History of BADBIR BADBIR Pilot phase Completed n = 143 Dec 2006Aug 2007 Aug 2008 Mar 2007 BADBIR Pilot phase started Apr 2007 MREC Approval achieved MREC submission BADBIR 1st patient recruited Jul 2008 BADBIR Main study

7. Aim of BADBIR  To investigate the long-term outcome of psoriasis patients treated with biologic agents, with particular reference to safety  Primary endpoints of interest  malignancy  infection requiring hospitalisation  serious adverse events  death

8. BADBIR Study Design Observational Cohort Study Inclusion Criteria (both biologic and conventional cohorts)  Diagnosis of psoriasis  Aged 16 years or over  Willing to provide written informed consent  Under the care of a dermatologist

9. BADBIR Study Design Observational Cohort Study Inclusion Criteria (both cohorts)  Diagnosis of psoriasis  Aged 16 years or over  Willing to provide written informed consent  Under the care of a dermatologist Biologic Cohort Starting / switching BIOLOGIC therapy in last 6 months  adalimumab  etanercept  infliximab  ustekinumab

10. BADBIR Study Design Observational Cohort Study Inclusion Criteria (both cohorts)  Diagnosis of psoriasis  Aged 16 years or over  Willing to provide written informed consent  Under the care of a dermatologist Biologic Cohort Conventional cohort (anti-psoriatic therapy) vs. Starting / switching BIOLOGIC therapy in last 6 months  adalimumab  etanercept  infliximab  ustekinumab Starting* / switching CONVENTIONAL therapy in last 6 months  acitretin  ciclosporin  fumaric acid esters  hydroxycarbamide  methotrexate  PUVA Conventional cohort additional criteria: Must be biologic naive * If starting therapy, PASI ≥10 and a DLQI >10

11. Dermatology Team questionnaire 6 MonthlyAnnually 5 YEARS Patient questionnaire & diary LIFE LONG Year 0Year 3Year 5 NHS Information Centre (NHSIC) flagging 6 Monthly 5 YEARS Annually Study Design – Follow-up

12. Switching between cohorts Biologic therapy Anti-psoriatic therapy 061218243036 Drug Time (months) Time contributed to comparison cohort Time contributed to biologic cohort

13. Sample Size Calculation Power to detect a 3-4 fold increase in skin cancer Baseline risk in psoriasis Non melanoma skin cancer = 100/100,000pyrs Accounting for losses to follow-up and deaths, requires: Biologic Conventional N = 4000 ( per drug) N = 4000

14. Online Data Collection Process (secure site login) www.badbir.org

15. BADBIR Database Security Model

16. Data collected at baseline Dermatology Team diagnosis and disease characteristics PASI previous & current systemic therapies (only tacrolimus or pimecrolimus topically) co-morbidities Patient Demographics including occupational status smoking history History of alcohol intake History of prior extensive sun exposure (e.g. outdoor work) Patient Reported Outcome Measures  Dermatology Life Quality Index (DLQI)  EuroQol (EQ-5D)  Cut Down Angry Guilty Early Morning (CAGE)  Health Assessment Questionnaire (HAQ - if co-existing inflammatory arthritis)

17. Data collected at follow up Dermatology Team changes in therapy adverse event information current disease activity Patient 6 monthly summary diary (hospitalisations, new drugs, referrals) Patient Reported Outcome Measures  DLQI  EQ-5D  CAGE  HAQ (if applicable)

18. Dermatology Centre: Patient Summary Screen

19. Extra Work Involved Identify and consent patient Complete baseline questionnaire and enter onto web-based database Complete follow-up forms and enter onto web-based database BADBIR Financial Assistance – 6 monthly intervals £120 per baseline questionnaire £30 per follow-up questionnaire Collection of data Financial assistance available Recruiting 2 patients per month 24 patients in year 1 Baseline @ £120 = £2880 12 F-up @ £30 ea = £360 Total in year 1 = £3240 Recruiting 8 patients per month 96 patients in year 1 Baseline @ £120 = £11520 48 F-up @ £30 ea = £1440 Total in year 1 = £12,960

20. 3 easy steps to getting involved ! Apply for R & D approval Step 1 Step 2 Evaluate your dermatology centre infrastructure Consider how BADBIR will be integrated into standard care The BADBIR Study Co-ordinator will visit to provide the user name and password and training on the on-line data collection process Step 3 Contact BADBIR – we will prepare all documentation You are now ready to register patients www.badbir.org.uk Consider preparing a business case for a specialist nursing service to assist in management of patients on biologic/systemic therapy Post R & D Approval It is essential that all relevant staff are present for this meeting

21. BADBIR in the UK and Eire

22. The BADBIR Team Contact ian.evans@manchester.ac.uk If you are interested in participating in BADBIR Dr Nicki Lawes BAD Biologics Manager

23. In conclusion: BADBIR Will help to answer important questions about long-term safety of both biologic and systemic anti- psoriatic therapy Enable us to provide more accurate, better quality information to patients commencing both the biologic and the conventional treatments

24. The dermatology teams for their efforts in registering patients BAD was provided with restricted income financial support from Abbott, Wyeth and Schering Plough to set-up BADBIR BAD commissioned the University of Manchester to set-up BADBIR with this financial support Acknowledgements