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• potential for serious side effects– efalizumab (marketing license withdrawn in 2009) – anti-TNF agents (serious infections e.g.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