BADBIR BAD Biologic Interventions Register Dr Kathy McElhone 27 th June 2012.
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Transcript of BADBIR BAD Biologic Interventions Register Dr Kathy McElhone 27 th June 2012.
BADBIR
BAD Biologic Interventions Register
Dr Kathy McElhone27th June 2012
Presentation Overview
• BADBIR Project rationale
• Brief history of BADBIR
• Aim and study design
• Data collection
• Conclusions
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• potential for serious side effects– efalizumab (marketing license withdrawn in 2009) – anti-TNF agents (serious infections e.g.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)
How is Potential Harm of Biologic Therapy assessed?
Phase I/II– Phase III
• Spontaneous pharmacovigilance
• Observational cohortsNational 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
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
Brief History of BADBIR
BADBIRPilot phaseCompletedn = 143
Dec
200
6
Au
g 2
007
Au
g 2
008
Mar
200
7
BADBIR Pilot phase started
Ap
r 20
07MREC Approval achieved
MREC submission
BADBIR 1st patientrecruited
Jul
2008
BADBIRMain study
Macclesfield District General
Aberdeen Royal
Infirmary
Hope Hospital, Manchester
Leigh Infirmary,
Lancs.
St Johns Institute, London
Royal Victoria
Infirmary, Newcastle
Western Infirmary,Glasgow
Aim of BADBIR
To investigate the long-term outcome of psoriasis patients treated with biologic agents, with particular reference to safety
Primary endpoints of interestmalignancy infection requiring hospitalisation serious adverse eventsdeath
BADBIR Study DesignObservational 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
BADBIR Study DesignObservational Cohort Study
Inclusion Criteria (both cohorts)Diagnosis of psoriasisAged 16 years or overWilling to provide written informed
consentUnder the care of a dermatologist
Biologic Cohort
Starting / switching BIOLOGIC therapy in
last 6 months
adalimumab
etanercept
infliximab
ustekinumab
BADBIR Study DesignObservational Cohort Study Inclusion Criteria (both cohorts)
Diagnosis of psoriasisAged 16 years or overWilling to provide written informed
consentUnder 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
Dermatology Team
questionnaire
6 Monthly Annually
5 YEARS
Patient questionnaire
& diary
LIFE LONG
Year 0 Year 3 Year 5
Flagging for occurrence of malignancy and/or death
6 Monthly
5 YEARS
Annually
Study Design – Follow-up
Switching between cohorts
Biologic therapy
Anti-psoriatic therapy
0 6 12 18 24 30 36
Drug
Time (months)
Time contributed to comparison cohort
Time contributed to biologic cohort
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
BADBIR Database Security Model
BASELINE
Data collected at baseline
DemographicsOccupational StatusSmoking HistoryPatient reported outcome measures:(DLQI, EQ-5D, CAGEHAQ 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
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)
• 130 Centres currently recruiting
• 5 in application at R&D departments
• 9 centres approved, set-up but yet to recruit
Biologics Conventional0
500
1000
1500
2000
2500
3000
3500
3100
1638
Total BADBIR Recruitment (17/05/2012)
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
BAD
BADBIR an achievement of olympic proportions
CLRN/R&DPharma
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