1. BADBIR BAD Biologic Interventions Register Dr Kathy McElhone 27 th June 2012

2. Presentation Overview BADBIR 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and patients –Concerns relatively high cost potential for serious side effects –efalizumab (marketing license withdrawn in 2009) –anti-TNF agents (serious infections e.g. tuberculosis, certain malignancies e.g. lymphomas, demyelinating disorders, congestive heart failure)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 and NICE All patients treated with biologic agents be registered with BADBIR

7. 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

8. 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

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

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 Starting / switching BIOLOGIC therapy in last 6 months  adalimumab  etanercept  infliximab  ustekinumab

11. 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

12. Dermatology Team questionnaire 6 MonthlyAnnually 5 YEARS Patient questionnaire & diary LIFE LONG Year 0Year 3Year 5 Flagging for occurrence of malignancy and/or death 6 Monthly 5 YEARS Annually Study Design – Follow-up

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

14. 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

15. BADBIR Database Security Model

17. BASELINE Data collected at baseline Demographics Occupational Status Smoking History Patient reported outcome measures: (DLQI, EQ-5D, CAGE HAQ if co-existing IA) Patient Diary Disease Characteristics PASI Current/Previous therapies Co-morbidities DERMATOLOGY TEAM PATIENT Clinician register patient onto BADBIR database Consent form faxed to BADBIR Eligible patient signs consent form

18. FOLLOW UP Data collected at each follow-up Patient attends follow — up visit DERMATOLOGY TEAM PATIENT Changes to therapy Adverse events Current disease activity Patient Reported Outcome Measures: (DLQI, EQ-5D, CAGE, HAQ if co-existing IA) Patient Diary (hospitalisations, referrals, new drugs)

19. 130 Centres currently recruiting 5 in application at R&D departments 9 centres approved, set-up but yet to recruit

21. In conclusion: BADBIR BADBIR established primarily to assess long term safety of biologic agents Other questions –attrition rates of the biologic therapies –effectiveness of second and subsequent treatments will be available –may assist in the development of future guidelines of care. –data on the relative safety and effectiveness in large numbers of patients treated with systemic agents such as methotrexate and ciclosporin. BADBIR for future studies e.g. pharmacogenetic, treatment concordance Answers to these questions will enable clinicians to provide more accurate, better quality information to patients commencing both the biologic and the conventional treatments

23. BAD BADBIR an achievement of olympic proportions CLRN/R&D Pharma Patients and Dermatology Teams UoM http://www.cks.nhs.uk/psoriasis http://www.bad.org.uk/site/622/default.aspx The dermatology teams for their efforts in registering patients BAD was provided with restricted income financial support from Abbott, Pfizer, MSD and Janssen Cilag to set-up BADBIR BAD commissioned the University of Manchester to set-up BADBIR with this financial support Acknowledgements