BAD Biologic Interventions Register (BADBIR )

An updateNovember 2009

Presentation Overview• 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– efalizumab (recently had marketing license withdrawn) – anti-TNF agents (serious infections e.g. tuberculosis,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

All patients treated with biologic agents be registered with BADBIR

Brief History of BADBIR

BADBIRPilot phaseCompleted

n = 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 2

008

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 biologic and conventional 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 psoriasis

Aged 16 years or over

Willing to provide written informed consent

Under the care of a dermatologist

Biologic CohortStarting / switching

BIOLOGIC therapy in last 6 months

adalimumab

etanercept

infliximab

ustekinumab

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

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

NHS Information Centre (NHSIC)

flagging

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

Online Data Collection Process(secure site login)

www.badbir.org

BADBIR Database Security Model

Data collected at baseline

Dermatology Team

diagnosis and disease characteristics

PASI

previous & current systemic therapies (only tacrolimus or pimecrolimus topically)

co-morbidities

PatientDemographics including

occupational status smoking historyHistory of alcohol intakeHistory of prior extensive sun exposure (e.g. outdoor work)

Patient Reported Outcome MeasuresDermatology Life Quality Index (DLQI)EuroQol (EQ-5D)Cut Down Angry Guilty Early Morning (CAGE)Health Assessment Questionnaire (HAQ - if co-existing inflammatory arthritis)

Data collected at follow up

Dermatology Team

changes in therapyadverse event informationcurrent disease activity

Patient6 monthly summary diary (hospitalisations, new drugs, referrals)

Patient Reported Outcome MeasuresDLQIEQ-5DCAGEHAQ (if applicable)

Dermatology Centre: Patient Summary Screen

Extra Work InvolvedIdentify and consent patientComplete baseline questionnaire and enter onto web-based databaseComplete 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 1Baseline @ £120 = £2880

12 F-up @ £30 ea = £360

Total in year 1 = £3240

Recruiting 8 patients per month 96 patients in year 1Baseline @ £120 = £11520 48 F-up @ £30 ea = £1440 Total in year 1 = £12,960

3 easy steps to getting involved !

Apply for R & D approvalStep 1

Step 2 Evaluate your dermatology centre infrastructureConsider 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

BADBIR in the UK and Eire

The BADBIR Team

Contact ian.evans@manchester.ac.uk

If you are interested in participating in BADBIR

Dr Nicki LawesBAD Biologics Manager

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

• 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